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Embryology
Embryology

Ronald W. Dudek, Ph.D.

Professor
Department of Anatomy and Cell Biology
Brody School of Medicine
East Carolina University
Greenville, North Carolina
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 Preface

The sixth edition of BRS Embryology includes improvements based on suggestions and
comments from the many medical students who have used this book in preparation for
the USMLE Step 1 examination and those students who have reviewed the book. I pay
close attention to these suggestions and comments in order to improve the quality of this
book. The goal of BRS Embryology is to provide an accurate and quick review of important
clinical aspects of embryology for the future physician. In addition, we have added color
to the diagrams. In this regard, I have used the following color scheme. The ectoderm/
neuroectoderm and derivatives are colored blue. The neural crest cells and derivatives are
colored purple. The mesoderm and derivatives are colored red. When multiple mesoder-
mal structures are involved (e.g., reproductive systems), I used light red and dark red. The
endoderm and derivatives are colored yellow.
Many times in the history of science, certain biological concepts become entrenched
and accepted as dogma even though recent evidence comes to light to challenge these con-
cepts. One of these concepts is the process of twinning. Recent evidence calls into question
the standard figures used in textbooks on how the process of twinning occurs. In particular,
it is becoming increasingly difficult to ignore the fact that dizygotic twins are sometimes
monochorionic. Although we by far do not know or attempt to explain exactly how twinning
occurs, it seems that the interesting cell and molecular events involved in twinning occur
in the first few cell divisions during first three or four days after fertilization. You are not a
twin because the inner cell mass splits. The inner cell mass splits because you are a twin.
This evidence warrants a new twinning figure (Figure 6.6) that does not comport with the
standard figures but tries to embrace recent evidence, although many may call it controver-
sial. Progress in our scientific understanding of twinning will never occur if our concept of
the twinning process is overly simplistic and reinforced by standard figures repeated over
and over in textbooks. Some published references that speak to this twinning issue include
Boklage,1,2 Yoon et al.,3 Williams et al.,4 and Hoekstra et al.5
I understand that BRS Embryology is a review book designed for a USMLE Step 1 review
and that you will not be faced with a question regarding this twinning concept, but I know
my readers are sophisticated enough to appreciate the scientific and clinical value of being
challenged to question traditional concepts as “grist for the mill” in discussions with your
colleagues.
I would appreciate receiving your comments and/or suggestions concerning BRS Em-
bryology sixth edition, especially after you have taken the USMLE Step 1 examination. Your
suggestions will find their way into the seventh edition. You may contact me at dudekr@
ecu.edu.
Ronald W. Dudek, PhD

v
vi Preface

REFERENCES
1. Boklage CE. Traces of embryogenesis are the same in monozygotic and dizygotic twins: not
compatible with double ovulation. Hum Reprod. 2009;24(6):1255–1266.
2. Boklage CE. How New Humans Are Made: Cells and Embryos, Twins and Chimeras, Left and
Right, Mind/Self/Soul, Sex, and Schizophrenia. Hackensack, NJ: World Scientific Publishing;
2010.
3. Yoon G, Beischel LS, Johnson JP, et al. Dizygotic twin pregnancy conceived with assisted repro-
ductive technology associated with chromosomal anomaly, imprinting disorder, and monocho-
rionic placentation. J Pediatr. 2005;146:565–567.
4. Williams CA, Wallace MR, Drury KC, et al. Blood lymphocyte chimerism associated with IVF
and monochorionic dizygous twinning: case report. Hum Reprod. 2004;19(12):2816–2821.
5. Hoekstra C, Zhao ZZ, Lambalk CB, et al. Dizygotic twinning. Hum Reprod Update.
2008;14(1):37–47.
 Contents

Preface v

1. PREFERTILIZATION EVENTS 1
I.Sexual Reproduction 1
II.Chromosomes 1
III.Meiosis 2
IV. Oogenesis: Female Gametogenesis 2
V. Spermatogenesis: Male Gametogenesis 4
VI. Clinical Considerations 4
Study Questions for Chapter 1 8
Answers and Explanations 10

2. WEEK 1 OF HUMAN DEVELOPMENT (DAYS 1–7) 12

I.Fertilization 12
II.Cleavage and Blastocyst Formation 13
III.Implantation 14
IV. Clinical Considerations 14
Study Questions for Chapter 2 15
Answers and Explanations 17

3. WEEK 2 OF HUMAN DEVELOPMENT (DAYS 8–14) 18

I.Further Development of the Embryoblast 18
II.Further Development of the Trophoblast 18
III.Development of Extraembryonic Mesoderm 20
IV. Clinical Considerations 20
Study Questions for Chapter 3 22
Answers and Explanations 24

4. EMBRYONIC PERIOD (WEEKS 3–8) 26

I. General Considerations 26
II. Further Development of the Embryoblast 26
vii
viii Contents

III. Vasculogenesis (De Novo Blood Vessel Formation) 28

IV. Hematopoiesis (Blood Cell Formation) 31
V. Clinical Considerations 31
Study Questions for Chapter 4 33
Answers and Explanations 35

5. CARDIOVASCULAR SYSTEM 37
I.Formation of Heart Tube 37
II.Primitive Heart Tube Dilations 37
III.The Aorticopulmonary Septum 39
IV. The Atrial Septum 41
V. The Atrioventricular Septum 43
VI. The Interventricular Septum 45
VII. The Conduction System of the Heart 46
VIII. Coronary Arteries 47
IX. Development of the Arterial System 47
X. Development of the Venous System 49
Study Questions for Chapter 5 50
Answers and Explanations 53

6. PLACENTA AND AMNIOTIC FLUID 55

I. Formation of the Placenta 55
II. Placental Components: Decidua Basalis
and Villous Chorion 55
III.Placental Membrane 58
IV. The Placenta as an Endocrine Organ 59
V. The Umbilical Cord 60
VI. Circulatory System of the Fetus 60
VII. Amniotic Fluid 62
VIII. Twinning 62
IX. Clinical Considerations 65
Study Questions for Chapter 6 68
Answers and Explanations 70

7. NERVOUS SYSTEM 71
I. Overview 71
II. Development of the Neural Tube 71
III. Neural Crest Cells 73
IV. Placodes 75
V. Vesicle Development of the Neural Tube 75
VI. Histogenesis of the Neural Tube 76
VII. Layers of the Early Neural Tube 78
 Contents ix

VIII. Development of the Spinal Cord 78

IX. Development of the Myelencephalon 79
X. Development of the Metencephalon 80
XI. Development of the Mesencephalon 81
XII. Development of the Diencephalon, Optic Structures,
and Hypophysis 82
XIII. Development of the Telencephalon 83
XIV. Development of the Sympathetic Nervous System 85
XV. Development of the Parasympathetic Nervous System 85
XVI. Development of the Cranial Nerves 86
XVII. Development of the Choroid Plexus 86
XVIII. Congenital Malformations of the Central Nervous System 87
Study Questions for Chapter 7 93
Answers and Explanations 96

8. EAR 98
I. Overview 98
II. The Internal Ear 98
III. The Membranous and Bony Labyrinths 100
IV. Middle Ear 100
V. External Ear 101
VI. Congenital Malformations of the Ear 101
Study Questions for Chapter 8 104
Answers and Explanations 105

9. EYE 106
I. Development of the Optic Vesicle 106
II. Development of other Eye Structures 109
III. Congenital Malformations of the Eye 110
Study Questions for Chapter 9 113
Answers and Explanations 114

10. DIGESTIVE SYSTEM 115

I.Overview 115
II.Derivatives of the Foregut 115
III.Derivatives of the Midgut 123
IV. Derivatives of the Hindgut 127
V. Anal Canal 130
VI. Mesenteries 130
Study Questions for Chapter 10 131
Answers and Explanations 133
x Contents

11. RESPIRATORY SYSTEM 134

I. Upper Respiratory System 134
II. Lower Respiratory System 134
Study Questions for Chapter 11 142
Answers and Explanations 143

12. HEAD AND NECK 144

I. Pharyngeal Apparatus 144
II. Development of the Thyroid Gland 144
III. Development of the Tongue 146
IV. Development of the Face 147
V. Development of the Palate 148
VI. Development of the Mouth 149
VII. Development of the Nasal Cavities 149
VIII. Clinical Considerations 150
Study Questions for Chapter 12 153
Answers and Explanations 154

13. URINARY SYSTEM 155

I.Overview 155
II.Development of the Metanephros 155
III.Relative Ascent of the Kidneys 156
IV. Blood Supply of the Kidneys 157
V. Development of the Urinary Bladder 158
VI. Development of the Female Urethra 159
VII. Development of the Male Urethra 160
VIII.Clinical Considerations 160
IX. Development of the Suprarenal Gland 164
Study Questions for Chapter 13 167
Answers and Explanations 168

14. FEMALE REPRODUCTIVE SYSTEM 169

I.The Indifferent Embryo 169
II.Development of the Gonads 169
III.Development of the Genital Ducts 171
IV. Development of the Primordia of External Genitalia 173
V. Tanner Stages of Female Sexual Development 174
VI. Clinical Considerations 174
Study Questions for Chapter 14 178
Answers and Explanations 179
 Contents xi

15. MALE REPRODUCTIVE SYSTEM 180

I.The Indifferent Embryo 180
II.Development of the Gonads 180
III.Development of the Genital Ducts 182
IV. Development of the Primordia of External Genitalia 184
V. Tanner Stages of Male Sexual Development 184
VI. Clinical Considerations 184
VII. Summary 189
Study Questions for Chapter 15 190
Answers and Explanations 191

16. INTEGUMENTARY SYSTEM 192

I.Skin 192
II.Hair and Nails 196
III.Mammary, Sweat, and Sebaceous Glands 199
IV. Teeth 201
Study Questions for Chapter 16 203
Answers and Explanations 204

17. SKELETAL SYSTEM 205

I.Skull 205
II.Vertebral Column 209
III.Ribs 214
IV. Sternum 214
V. Bones of the Limbs and Limb Girdles 214
VI. Osteogenesis 215
VII. General Skeletal Abnormalities 215
Study Questions for Chapter 17 218
Answers and Explanations 219

18. MUSCULAR SYSTEM 220

I.Skeletal Muscle 220
II.Smooth Muscle 221
III.Cardiac Muscle 222
IV. Clinical Considerations 222
Study Questions for Chapter 18 224
Answers and Explanations 225
xii Contents

19. UPPER LIMB 226

I.Overview of Development 226
II.Vasculature 226
III.Musculature 228
IV. Nerves: The Brachial Plexus 228
V. Rotation of the Upper Limb 229
VI. Skeletal 229
Study Questions for Chapter 19 231
Answers and Explanations 232

20. LOWER LIMB 233

I.Overview of Development 233
II.Vasculature 233
III.Musculature 235
IV. Nerves: The Lumbosacral Plexus 235
V. Rotation of the Lower Limb 236
VI. Skeletal 237
Study Questions for Chapter 20 239
Answers and Explanations 240

21. BODY CAVITIES 241

I.Formation of the Intraembryonic Coelom 241
II.Partitioning of the Intraembryonic Coelom 241
III.Positional Changes of the Diaphragm 242
IV. Clinical Considerations 243
Study Questions for Chapter 21 244
Answers and Explanations 245

22. PREGNANCY 246

I.Endocrinology of Pregnancy 246
II.Pregnancy Dating 247
III.Pregnancy Milestones 247
IV. Prenatal Diagnostic Procedures 248
V. Fetal Distress During Labor (Intrapartum) 249
VI. The Apgar Score 249
VII. Puerperium 250
VIII. Lactation 250
IX. Small-for-Gestational Age (SGA) Infant 250
X. Collection and Storage of Umbilical Cord Blood (UCB) 251
Study Questions for Chapter 22 252
Answers and Explanations 253
 Contents xiii

23. TERATOLOGY 254

I.
Introduction 254
II.
Infectious Agents 254
III.
Torch Infections 256
IV.
Childhood Vaccinations 258
V.
Category X Drugs (Absolute Contraindication In Pregnancy) 258
VI.
Category D Drugs (Definite Evidence of Risk to Fetus) 259
VII.
Chemical Agents 260
VIII.
Recreational Drugs 261
IX.
Ionizing Radiation 261
Study Questions for Chapter 23 262
Answers and Explanations 263

Comprehensive Examination 264

Answers and Explanations 272
Credits 279
Index 287
chapter
1 Prefertilization Events

I. SEXUAL REPRODUCTION
Sexual reproduction occurs when female and male gametes (oocyte and spermatozoon, respectively)
unite at fertilization. Gametes are direct descendants of primordial germ cells, which are first
observed in the wall of the yolk sac at week 4 of embryonic development and subsequently migrate
into the future gonad region. Gametes are produced by gametogenesis (called oogenesis in the
female and spermatogenesis in the male). Gametogenesis employs a specialized process of cell divi-
sion, meiosis, which uniquely distributes chromosomes among gametes.

II. CHROMOSOMES (FIGURE 1.1)

A single chromosome consists of two characteristic regions called arms (p arm = short arm;
q arm = long arm), which are separated by a centromere. During meiosis I, single chromosomes
undergo DNA replication, which duplicates the arms. This forms duplicated chromosomes, which
consist of two sister chromatids attached at the centromere.

A. Ploidy and N number. Ploidy refers to the number of chromosomes in a cell. The N number refers to
the amount of DNA in a cell.
1. Normal somatic cells and primordial germ cells contain 46 single chromosomes and 2N amount
of DNA. The chromosomes occur in 23 homologous pairs; one member (homologue) of each
pair is of maternal origin, and the other is of paternal origin. The term “diploid” is classically
used to refer to a cell containing 46 single chromosomes. Chromosome pairs 1–22 are
autosomal (nonsex) pairs. Chromosome pair 23 consists of the sex chromosomes (XX for a
female and XY for a male).
2. Gametes contain 23 single chromosomes (22 autosomes and 1 sex chromosome) and 1N
amount of DNA. The term “haploid” is classically used to refer to a cell containing 23 single
chromosomes. Female gametes contain only the X sex chromosome. Male gametes contain
either the X or Y sex chromosome; therefore, the male gamete determines the genetic sex of
the individual.

B. The X chromosome. A normal female somatic cell contains two X chromosomes (XX). The female
cell permanently inactivates one of the X chromosomes during week 1 of embryonic development.
The choice of which X chromosome (maternal or paternal) is inactivated is random. The

1
2 BRS Embryology

Chromatid 1 Chromatid 2
FIGURE 1.1. A schematic diagram of
chromosome 18 showing it in its “single-
p arm chromosome” state and in the “dupli-
cated-chromosome” state that is formed
DNA replication by DNA replication during meiosis I. It is
important to understand that both the
Meiosis I “single-chromosome” state and the
Centromere Centromere
“duplicated-chromosome” state will be
counted as one chromosome 18. As long
q arm as the additional DNA in the “duplicated
chromosome” is bound at the centro-
mere, the structure will be counted as
Chromosome 18 Chromosome 18 one chromosome 18 even though it has
“single chromosome” “duplicated chromosome” twice the amount of DNA.

inactivated X chromosome (called the Barr body) can be observed by light microscopy near the
nuclear membrane.

C. The Y chromosome. A normal male somatic cell contains one X chromosome and one Y chromosome
(XY).

III. MEIOSIS
Meiosis is a specialized process of cell division that occurs only during the production of gametes
within the female ovary or male testes. Meiosis consists of two divisions (meiosis I and II), which
result in the formation of four gametes, each containing half the number of chromosomes (23 single
chromosomes) and half the amount of DNA (1N) found in normal somatic cells (46 single chromo-
somes, 2N).

A. Meiosis I. Events that occur during meiosis I include the following:

1. Synapsis: pairing of 46 homologous duplicated chromosomes.
2. Crossing over: exchange of large segments of DNA.
3. Alignment: alignment of 46 homologous duplicated chromosomes at the metaphase plate.
4. Disjunction: separation of 46 homologous duplicated chromosomes from each other;
centromeres do not split.
5. Cell division: formation of two secondary gametocytes (23 duplicated chromosomes, 2N).

B. Meiosis II. Events that occur during meiosis II include the following:
1. Synapsis: absent.
2. Crossing over: absent.
3. Alignment: alignment of 23 duplicated chromosomes at the metaphase plate.
4. Disjunction: separation of 23 duplicated chromosomes to form 23 single chromosomes;
centromeres split.
5. Cell division: formation of four gametes (23 single chromosomes, 1N).

IV. OOGENESIS: FEMALE GAMETOGENESIS (FIGURE 1.2)

A. Primordial germ cells (46, 2N) from the wall of the yolk sac arrive in the ovary at week 6 and
differentiate into oogonia (46, 2N), which populate the ovary through mitotic division.

B. Oogonia enter meiosis I and undergo DNA replication to form primary oocytes (46, 4N). All primary
oocytes are formed by month 5 of fetal life. No oogonia are present at birth.
 Chapter 1 Prefertilization Events 3

Oogonia
(46 single chromosomes, 2N)

DNA Replication Meiosis I

Dormant in dictyotene
Primary oocyte
of meiosis I until puberty
(46 duplicated chromosomes, 4N)

Synapsis

Crossing over
Chiasma

Alignment and disjunction

Centromeres do not split

Secondary oocyte
(23 duplicated chromosomes, 2N) 1st polar body

Meiosis II

Alignment and disjunction Arrested in metaphase

Centromeres split of meiosis II

Cell division
Mature oocyte Fertilization
(23 single chromosomes, 1N) 2nd polar body

FIGURE 1.2. Oogenesis: female gametogenesis. Note that only one pair of homologous chromosomes is shown (red,
maternal origin; blue, paternal origin). Synapsis is the process of pairing of homologous chromosomes. The point at which
the DNA molecule crosses over is called the chiasma and is where exchange of small segments of maternal and paternal
DNA occurs. Note that synapsis and crossing over occur only during meiosis I. The polar bodies are storage bodies for
DNA unnecessary for the further function of the cell and probably degenerate. There is no evidence that polar bodies
divide or undergo any other activity.

C. Primary oocytes remain dormant in prophase (dictyotene) of meiosis I from month 5 of fetal life
until puberty. After puberty, 5 to 15 primary oocytes begin maturation with each ovarian cycle,
with usually only 1 reaching full maturity in each cycle.

D. During the ovarian cycle and triggered by the luteinizing hormone (LH) surge, a primary oocyte
completes meiosis I to form two daughter cells: the secondary oocyte (23, 2N) and the first polar
body, which degenerates.

E. The secondary oocyte promptly begins meiosis II but is arrested in metaphase of meiosis II about
3 hours before ovulation. The secondary oocyte remains arrested in metaphase of meiosis II until
fertilization occurs.
4 BRS Embryology

F. At fertilization, the secondary oocyte completes meiosis II to form a mature oocyte (23, 1N) and a
second polar body.

G. Approximate number of oocytes

1. Primary oocytes: At month 5 of fetal life, 7 million primary oocytes are present. At birth,
2 million are present (5 million have degenerated). At puberty, 40,000 are present (1.96 million
more have degenerated).
2. Secondary oocytes: Twelve secondary oocytes are ovulated per year, up to 480 over the entire
reproductive life of the woman (40 years × 12 secondary oocytes per year = 480). This number
(480) is obviously overly simplified since it is reduced in women who take birth control
pills (which prevent ovulation), in women who become pregnant (ovulation stops during
pregnancy), and in women who may have anovulatory cycles.

V. SPERMATOGENESIS: MALE GAMETOGENESIS (FIGURE 1.3)

Spermatogenesis is classically divided into three phases:

A. Spermatocytogenesis
1. Primordial germ cells (46, 2N) from the wall of the yolk sac arrive in the testes at week 6 and
remain dormant until puberty. At puberty, primordial germ cells differentiate into type A
spermatogonia (46, 2N).
2. Type A spermatogonia undergo mitosis to provide a continuous supply of stem cells
throughout the reproductive life of the male. Some type A spermatogonia differentiate into
type B spermatogonia (46, 2N).

B. Meiosis
1. Type B spermatogonia enter meiosis I and undergo DNA replication to form primary
spermatocytes (46, 4N).
2. Primary spermatocytes complete meiosis I to form secondary spermatocytes (23, 2N).
3. Secondary spermatocytes complete meiosis II to form four spermatids (23, 1N).

C. Spermiogenesis
1. Spermatids undergo a postmeiotic series of morphological changes to form sperm (23, 1N).
These changes include the (a) formation of the acrosome, (b) condensation of the nucleus, and
(c) formation of head, neck, and tail. The total time of sperm formation (from spermatogonia
to spermatozoa) is about 64 days.
2. Newly ejaculated sperm are incapable of fertilization until they undergo capacitation,
which occurs in the female reproductive tract and involves the unmasking of sperm
glycosyltransferases and the removal of adherent plasma proteins coating the surface of the
sperm.

VI. CLINICAL CONSIDERATIONS

A. Offspring of older women
1. Prolonged dormancy of primary oocytes may be the reason for the high incidence of
chromosomal abnormalities in the offspring of older women. Since all primary oocytes are
formed by month 5 of fetal life, a female infant is born with her entire supply of gametes. Primary
oocytes remain dormant until ovulation; those ovulated late in the woman’s reproductive life
may have been dormant for as long as 40 years.
2. The incidence of trisomy 21 (Down syndrome) increases with advanced age of the mother.
The primary cause of Down syndrome is maternal meiotic nondisjunction. Clinical findings
 Chapter 1 Prefertilization Events 5

Dormant until
Primordial germ cells puberty

Type A spermatogonia
Spermatocytogenesis

Type B spermatogonia
(46 single chromosomes, 2N)

DNA Replication Meiosis I

Primary spermatocyte
(46 duplicated chromosomes, 4N)

Synapsis

Crossing over
Chiasma

Alignment and disjunction

Centromeres do not split

Secondary spermatocyte
(23 duplicated chromosomes, 2N)

Meiosis II

Alignment and disjunction

Centromeres split

Cell division Cell division

Spermatids
(23 single chromosomes, 1N)

Spermiogenesis Sperm

FIGURE 1.3. Spermatogenesis: male gametogenesis. Note that only one pair of homologous chromosomes is shown (red,
maternal origin; blue, paternal origin). Synapsis is the process of pairing of homologous chromosomes. The point at which
the DNA molecule crosses over is called the chiasma and is where exchange of small segments of maternal and paternal
DNA occurs. Note that synapsis and crossing over occur only during meiosis I.
6 BRS Embryology

include moderate mental retardation, microcephaly, microphthalmia, colobomata, cataracts

and glaucoma, flat nasal bridge, epicanthal folds, protruding tongue, Brushfield spots, simian
crease in the hand, increased nuchal skin folds, congenital heart defects, and an association
with a decrease in α-fetoprotein.

B. Offspring of older men

An increased incidence of achondroplasia (a congenital skeletal anomaly characterized by retarded
bone growth) and Marfan syndrome are associated with advanced paternal age.

C. Male infertility
1. Sperm number and motility: Infertile males produce less than 10 million sperm/mL of semen.
Fertile males produce from 20 to more than 100 million sperm/mL of semen. Normally, up
to 10% of sperm in an ejaculate may be grossly deformed (two heads or two tails), but these
sperm probably do not fertilize an oocyte because of their lack of motility.
2. Hypogonadotropic hypogonadism is a condition where the hypothalamus produces reduced
levels of gonadotropin-releasing factor (GnRF), leading to reduced levels of follicle-stimulating
hormone (FSH) and LH, and finally, reduced levels of testosterone. Kallmann syndrome is
a genetic disorder characterized by hypogonadotropic hypogonadism and anosmia (loss of
smell).
3. Drugs: cancer chemotherapy, anabolic steroids, cimetidine (histamine H2-receptor antagonist
that inhibits stomach HCl production), spironolactone (a K+-sparing diuretic), phenytoin (an
antiepileptic drug), sulfasalazine (a sulfa drug used to treat ulcerative colitis, Crohn disease,
rheumatoid arthritis, and psoriatic arthritis), and nitrofurantoin (an antibiotic used to treat
urinary tract infections).
4. Other factors: Klinefelter syndrome (XXY), seminoma, cryptochordism, varicocele, hydrocele,
mumps, prostatitis, epididymitis, hypospadias, ductus deferens obstruction, and impotence.

D. Female infertility
1. Anovulation is the absence of ovulation in some women due to inadequate secretion of FSH
and LH and is often treated with clomiphene citrate (a fertility drug). Clomiphene citrate
competes with estrogen for binding sites in the adenohypophysis, thereby suppressing the
normal negative feedback loop of estrogen on the adenohypophysis. This stimulates FSH and
LH secretions and induces ovulation.
2. Premature ovarian failure (primary ovarian insufficiency) is the loss of function of the ovaries
before age 40, resulting in infertility. The cause is generally idiopathic, but cases have been
attributed to autoimmune disorders, Turner syndrome, Fragile X syndrome, chemotherapy,
or radiation treatment. The onset can be seen in early teenage years, but varies widely. If a girl
never begins menstruation, the condition is called primary ovarian failure. Clinical findings
include amenorrhea, low estrogen levels, high FSH levels, and small ovaries without follicles
(seen by ultrasound).
3. Pelvic inflammatory disease (PID) refers to the infection of the uterus, uterine tubes, and/
or ovaries leading to inflammation and scar formation. The cause is generally a sexually
transmitted infection (STI), usually by Neisseria gonorrhea or Chlamydia trachomatis;
however, many other reasons are possible (lymphatic spread, hematogenous spread,
postpartum infections, postabortal [miscarriage or abortion] infections, or intrauterine
device infections). Clinical findings include fever, tenderness of the cervix, lower abdominal
pain, discharge, painful intercourse, or irregular menstrual bleeding; some cases are
asymptomatic.
4. Polycystic ovarian syndrome is a complex female endocrine disorder defined by oligo-
ovulation (infrequent, irregular ovulations), androgen excess, multiple ovarian cysts (by
ultrasound). The cause is uncertain, but a strong genetic component exists. Clinical findings
include anovulation, irregular menstruation, amenorrhea, ovulation-related infertility, high
androgen levels or activity resulting in acne and hirsutism, insulin resistance associated with
obesity, and type 2 diabetes.
5. Endometriosis is the appearance of foci of endometrial tissue in abnormal locations outside
the uterus (e.g., ovary, uterine ligaments, pelvic peritoneum). The ectopic endometrial
 Chapter 1 Prefertilization Events 7

t a b l e 1.1 Chance of Pregnancy in Days Near Ovulation

Time Chance of Pregnancy (%)

5 days before ovulation 10

4 days before ovulation 16
3 days before ovulation 14
2 days before ovulation 27
1 day before ovulation 31
Day of ovulation 33
Day after ovulation 0

tissue shows cyclic hormonal changes synchronous with the cyclic hormonal changes of the
endometrium in the uterus. Clinical findings include infertility, dysmenorrhea, pelvic pain
(most pronounced at the time of menstruation), dysuria, painful sex, and throbbing pain in
the legs.

E. The estimated chance of pregnancy (fertility) in the days surrounding ovulation is shown in
Table 1.1.
8 BRS Embryology

Study Questions for Chapter 1

1. Which of the following is a major character- (D) A crossover chromosome

istic of meiosis I? (E) A homologous pair
(A) Splitting of the centromere
(B) Pairing of homologous chromosomes 6. All primary oocytes are formed by
(C) Reducing the amount of DNA to 1N (A) week 4 of embryonic life
(D) Achieving the diploid number of (B) month 5 of fetal life
chromosomes (C) birth
(E) Producing primordial germ cells (D) month 5 of infancy
(E) puberty
2. A normal somatic cell contains a total of 46
chromosomes. What is the normal complement 7. When does formation of primary spermato-
of chromosomes found in a sperm? cytes begin?
(A) 22 autosomes plus a sex chromosome (A) During week 4 of embryonic life
(B) 23 autosomes plus a sex chromosome (B) During month 5 of fetal life
(C) 22 autosomes (C) At birth
(D) 23 autosomes (D) During month 5 of infancy
(E) 23 paired autosomes (E) At puberty

3. Which of the following describes the num- 8. In the production of female gametes, which
ber of chromosomes and amount of DNA in a of the following cells can remain dormant for 12
gamete? to 40 years?
(A) 46 chromosomes, 1N (A) Primordial germ cell
(B) 46 chromosomes, 2N (B) Primary oocyte
(C) 23 chromosomes, 1N (C) Secondary oocyte
(D) 23 chromosomes, 2N (D) First polar body
(E) 23 chromosomes, 4N (E) Second polar body

4. Which of the following chromosome com- 9. In the production of male gametes, which
positions in a sperm normally results in the of the following cells remains dormant for 12
production of a genetic female if fertilization years?
occurs? (A) Primordial germ cell
(A) 23 homologous pairs of chromosomes (B) Primary spermatocyte
(B) 22 homologous pairs of chromosomes (C) Secondary spermatocyte
(C) 23 autosomes plus an X chromosome (D) Spermatid
(D) 22 autosomes plus a Y chromosome (E) Sperm
(E) 22 autosomes plus an X chromosome
10. Approximately how many sperm will be
5. In the process of meiosis, DNA replication of ejaculated by a normal fertile male during
each chromosome occurs, forming a structure sexual intercourse?
consisting of two sister chromatids attached to (A) 10 million
a single centromere. What is this structure? (B) 20 million
(A) A duplicated chromosome (C) 35 million
(B) Two chromosomes (D) 100 million
(C) A synapsed chromosome (E) 350 million

8
 Chapter 1 Prefertilization Events 9

11. A young woman enters puberty with (C) Alignment

approximately 40,000 primary oocytes in (D) Crossing over
her ovary. About how many of these pri- (E) Disjunction
mary oocytes will be ovulated over the entire
reproductive life of the woman? 15. During ovulation, the secondary oocyte
(A) 40,000 resides at what specific stage of meiosis?
(B) 35,000 (A) Prophase of meiosis I
(C) 480 (B) Prophase of meiosis II
(D) 48 (C) Metaphase of meiosis I
(E) 12 (D) Metaphase of meiosis II
(E) Meiosis is completed at the time of
12. Fetal sex can be diagnosed by noting the ovulation
presence or absence of the Barr body in cells
obtained from the amniotic fluid. What is the 16. Concerning maturation of the female gam-
etiology of the Barr body? ete (oogenesis), when do the oogonia enter
(A) Inactivation of both X chromosomes meiosis I and undergo DNA replication to form
(B) Inactivation of homologous chromosomes primary oocytes?
(C) Inactivation of one Y chromosome (A) During fetal life
(D) Inactivation of one X chromosome (B) At birth
(E) Inactivation of one chromatid (C) At puberty
(D) With each ovarian cycle
13. How much DNA does a primary spermato- (E) Following fertilization
cyte contain?
(A) 1N 17. Where do primordial germ cells initially
(B) 2N develop?
(C) 4N (A) In the gonads at week 4 of embryonic
(D) 6N development
(E) 8N (B) In the yolk sac at week 4 of embryonic
development
14. During meiosis, pairing of homologous (C) In the gonads at month 5 of embryonic
chromosomes occurs, which permits large seg- development
ments of DNA to be exchanged. What is this (D) In the yolk sac at month 5 of embryonic
process called? development
(A) Synapsis (E) In the gonads at puberty
(B) Nondisjunction
 Answers and Explanations

1. B. Pairing of homologous chromosomes (synapsis) is a unique event that occurs only dur-
ing meiosis I in the production of gametes. Synapsis is necessary so that crossing over can
occur.
2. A. A normal gamete (sperm in this case) contains 23 single chromosomes. These 23 chromo-
somes consist of 22 autosomes plus 1 sex chromosome.
3. C. Gametes contain 23 chromosomes and 1N amount of DNA, so that when two gametes fuse at
fertilization, a zygote containing 46 chromosomes and 2N amount of DNA is formed.
4. E. A sperm contains 22 autosomes and 1 sex chromosome. The sex chromosome in sperm may
be either the X chromosome or the Y chromosome. The sex chromosome in a secondary oocyte
is only the X chromosome. If an X-bearing sperm fertilizes a secondary oocyte, a genetic female
(XX) is produced. Therefore, sperm is the arbiter of sex determination.
5. A. The structure formed is a duplicated chromosome. DNA replication occurs, so that the
amount of DNA is doubled (2 × 2N = 4N). However, the chromatids remain attached to the cen-
tromere, forming a duplicated chromosome.
6. B. During early fetal life, oogonia undergo mitotic divisions to populate the developing ovary.
All the oogonia subsequently give rise to primary oocytes by month 5 of fetal life; at birth, no
oogonia are present in the ovary. At birth, a female has her entire supply of primary oocytes to
carry her through reproductive life.
7. E. At birth, a male has primordial germ cells in the testes that remain dormant until puberty, at
which time they differentiate into type A spermatogonia. At puberty, some type A spermatogo-
nia differentiate into type B spermatogonia and give rise to primary spermatocytes by undergo-
ing DNA replication.
8. B. Primary oocytes are formed by month 5 of fetal life and remain dormant until puberty, when
hormonal changes in the young woman stimulate the ovarian and menstrual cycles. From 5 to
15 oocytes will then begin maturation with each ovarian cycle throughout the woman’s repro-
ductive life.
9. A. Primordial germ cells migrate from the wall of the yolk sac during week 4 of embryonic
life and enter the gonad of a genetic male, where they remain dormant until puberty (about
age 12 years), when hormonal changes in the young man stimulate the production of
sperm.
10. E. A normal fertile male will ejaculate about 3.5 mL of semen containing about 100 million
sperm/mL (3.5 mL × 100 million = 350 million).
11. C. Over her reproductive life, a woman will ovulate approximately 480 oocytes. A woman will
ovulate 12 primary oocytes per year, provided that she is not using oral contraceptives, does not
become pregnant, or does not have any anovulatory cycles. Assuming a 40-year reproductive
period gives 40 × 12 = 480.
12. D. The Barr body is formed from inactivation of one X chromosome in a female. All somatic cells
of a normal female will contain two X chromosomes. The female has evolved a mechanism for
permanent inactivation of one of the X chromosomes presumably because a double dose of
X chromosome products would be lethal.
13. C. Type B spermatogonia give rise to primary spermatocytes by undergoing DNA replication,
thereby doubling the amount of DNA (2 × 2N = 4N) within the cell.

10
 Chapter 1 Prefertilization Events 11

14. D. Synapsis (pairing of homologous chromosomes) is a unique event that occurs only during
meiosis I in the production of gametes. Synapsis is necessary so that crossing over, whereby
large segments of DNA are exchanged, can occur.
15. D. The secondary oocyte is arrested in metaphase of meiosis II about 3 hours before ovulation,
and it remains in this meiotic stage until fertilization.
16. A. All primary oocytes are formed by month 5 of fetal life, so no oogonia are present at birth.
17. B. Primordial germ cells, the predecessors to gametes, are first seen in the wall of the yolk sac at
week 4 of embryonic development, and they migrate into the gonads at week 6.
 Week 1 of Human
chapter
2 Development (Days 1–7)*

I. FERTILIZATION
Fertilization occurs in the ampulla of the uterine tube and includes three phases.

A. Phase 1: Sperm penetration of corona radiata involves the action of both sperm and uterine tube
mucosal enzymes.

B. Phase 2: Sperm binding and penetration of the zona pellucida

1. Sperm binding occurs through the interaction of sperm glycosyltransferases and ZP3 receptors
located on the zona pellucida. Sperm binding triggers the acrosome reaction, which entails the
fusion of the outer acrosomal membrane and sperm cell membrane, resulting in the release of
acrosomal enzymes.
2. Penetration of the zona pellucida requires acrosomal enzymes, specifically acrosin. Sperm
contact with the cell membrane of a secondary oocyte triggers the cortical reaction, which
entails the release of cortical granules (lysosomes) from the oocyte cytoplasm. This reaction
changes the secondary oocyte cell membrane potential and inactivates sperm receptors
on the zona pellucida. These changes are called the polyspermy block, which renders the
secondary oocyte cell membrane impermeable to other sperm. However, efficiency of the
polyspermy block remains questionable since diandric triploidy (an embryo with three sets of
chromosomes, two of which come from the father) is quite common.

C. Phase 3: Fusion of sperm and oocyte cell membranes occurs with subsequent breakdown of both
membranes at the fusion area.
1. The entire sperm (except the cell membrane) enters the cytoplasm of the secondary oocyte
arrested in metaphase of meiosis II. The sperm nuclear contents and the centriole pair persist,
but the sperm mitochondria and tail degenerate. The sperm nucleus becomes the male
pronucleus. Since all sperm mitochondria degenerate, all mitochondria within the zygote
are of maternal origin (i.e., all mitochondrial DNA is of maternal origin). The oocyte loses its
centriole pair during meiosis so that the establishment of a functional zygote depends upon the
sperm centriole pair (a cardinal feature of human embryogenesis) to produce a microtubule-
organizing center (MTOC).

*The age of a developing conceptus can be measured either from the estimated day of fertilization (fertilization
age) or from the day of the last normal menstrual period (LNMP age). In this book, age is presented as the
fertilization age.

12
 Chapter 2 Week 1 of Human Development (Days 1–7) 13

2. The secondary oocyte completes meiosis II, forming a mature ovum and a second polar body.
The nucleus of the mature ovum is now called the female pronucleus.
3. Male and female pronuclei fuse, forming a zygote (a new cell whose genotype is a combination
of maternal and paternal chromosomes).
4. Syngamy is a term that describes the successful completion of fertilization, that is, the formation
of a zygote. Syngamy occurs when the male and female pronuclei fuse and the cytoplasmic
machinery for proper cell division exists.
5. The life span of a zygote is only a few hours because its existence terminates when the first
cleavage division occurs.

II. CLEAVAGE AND BLASTOCYST FORMATION (FIGURE 2.1)

A. Cleavage is a series of mitotic divisions of the zygote where the plane of the first mitotic division
passes through the area of the cell membrane where the polar bodies were previously extruded.
1. Cleavage in humans is holoblastic, which means the cells divide completely through their
cytoplasm. Cleavage in humans is asymmetrical, which means the daughter cells are unequal in
size (i.e., one cell gets more cytoplasm than the other) at least during the first few cell divisions.
Cleavage in humans is asynchronous, which means only one cell will divide at a time; generally,
the largest daughter cell will divide next at least during the first few cell divisions.
2. The process of cleavage eventually forms a blastula consisting of cells called blastomeres.

A 2-Cell 4-Cell Morula Blasotocyst

blastula blastula

Blastomere

Zygote

Fertilization Zona pellucida

Secondary
oocyte
arrested in
metaphase
Day 1 Day 7
B

Syncytiotrophoblast

Embryoblast
Cytotrophoblast
Blastocyst cavity

FIGURE 2.1. A. The stages of human development during week 1. B. A day 7 blastocyst.
14 BRS Embryology

3. A cluster of blastomeres (16–32 blastomeres) forms a morula.

4. Blastomeres are totipotent up to the eight-cell stage (i.e., each blastomere can form a complete
embryo by itself ). Totipotency refers to a stem cell that can differentiate into every cell within
the organism, including extraembryonic tissues.

B. Blastocyst formation involves fluid secreted within the morula that forms the blastocyst cavity. The
conceptus is now called a blastocyst.
1. The inner cell mass of the blastocyst is called the embryoblast (becomes the embryo). The
embryoblast cells are pluripotent. Pluripotency refers to a stem cell that can differentiate into
ectoderm, mesoderm, and endoderm.
2. The outer cell mass of the blastocyst is called the trophoblast (becomes the fetal portion of the
placenta).

C. Zona pellucida degeneration occurs by day 4 after conception. The zona pellucida must degenerate
for implantation to occur.

III. IMPLANTATION (FIGURE 2.1)

The blastocyst usually implants within the posterior superior wall of the uterus by day 7 after fertil-
ization. Implantation occurs in the functional layer of the endometrium during the progestational
(secretory) phase of the menstrual cycle. The trophoblast proliferates and differentiates into the cy-
totrophoblast and syncytiotrophoblast. Failure of implantation may involve immune rejection (graft-
versus-host reaction) of the antigenic conceptus by the mother.

IV. CLINICAL CONSIDERATIONS

A. Ectopic tubal pregnancy (ETP)
1. ETP occurs when the blastocyst implants within the uterine tube due to delayed transport.
2. The ampulla of the uterine tube is the most common site of an ectopic pregnancy. The
rectouterine pouch (pouch of Douglas) is a common site for an ectopic abdominal pregnancy.
3. ETP is most commonly seen in women with endometriosis or pelvic inflammatory disease.
4. ETP leads to uterine tube rupture and hemorrhage if surgical intervention (i.e., salpingectomy)
is not performed.
5. ETP presents with abnormal uterine bleeding, unilateral pelvic pain, increased levels of human
chorionic gonadotropin (hCG) (but lower than originally expected with uterine implantation
pregnancy), and a massive first-trimester bleed.
6. ETP must be differentially diagnosed from appendicitis, an aborting intrauterine pregnancy,
or a bleeding corpus luteum of a normal intrauterine pregnancy.

B. Testicular teratocarcinoma (TTC)

1. TTC is a germ cell neoplasm. In its early histologic stages, a TTC resembles a blastocyst with
three primary germ layers and may be loosely referred to as “male pregnancy.”
2. TTC contains well-differentiated cells and structures from each of the three primary germ
layers: for example, colon glandular tissue (endoderm), cartilage (mesoderm), and squamous
epithelium (ectoderm).
3. TTC also contains undifferentiated pluripotent stem cells called embryonic carcinoma (EC) cells.
4. TTC is associated with elevated α-fetoprotein levels.
5. TTC can be experimentally produced by implanting a blastocyst in an extrauterine site. The
ability of blastocysts to form TTC suggests a relationship between the inner cell mass and EC
cells. This relationship has been confirmed by isolation of cell lines from blastocysts called
embryonic stem (ES) cells, which have biochemical characteristics remarkably similar to
those of EC cells.
 Study Questions for Chapter 2

1. A 20-year-old woman presents at the emer- 5. Which of the following events is involved
gency department with severe abdominal in the cleavage of the zygote during week 1 of
pain on the right side with signs of internal development?
bleeding. She indicated that she has been (A) A series of meiotic divisions forming
sexually active without contraception and blastomeres
missed her last menstrual period. Based on (B) Production of highly differentiated
this information, which of the following dis- blastomeres
orders must be included as an option in the (C) An increased cytoplasmic content of
diagnosis? blastomeres
(A) Ovarian cancer (D) An increase in size of blastomeres
(B) Appendicitis (E) A decrease in size of blastomeres
(C) Normal pregnancy
(D) Ectopic tubal pregnancy 6. Which of the following structures must
(E) Toxemia of pregnancy degenerate for blastocyst implantation to
occur?
2. When does a secondary oocyte complete its (A) Endometrium in progestational phase
second meiotic division to become a mature (B) Zona pellucida
ovum? (C) Syncytiotrophoblast
(A) At ovulation (D) Cytotrophoblast
(B) Before ovulation (E) Functional layer of the endometrium
(C) At fertilization
(D) At puberty 7. Which of the following is the origin of the
(E) Before birth mitochondrial DNA of all human adult cells?
(A) Paternal only
3. How soon after fertilization occurs within (B) Maternal only
the uterine tube does the blastocyst begin (C) A combination of paternal and maternal
implantation? (D) Either paternal or maternal
(A) Within minutes (E) Unknown origin
(B) By 12 hours
(C) By day 1 8. Individual blastomeres were isolated from a
(D) By day 2 blastula at the 4-cell stage. Each blastomere was
(E) By day 7 cultured in vitro to the blastocyst stage and in-
dividually implanted into four pseudopregnant
4. Where does the blastocyst normally foster mothers. Which of the following would
implant? you expect to observe 9 months later?
(A) Functional layer of the cervix (A) Birth of one baby
(B) Functional layer of the endometrium (B) Birth of four genetically different babies
(C) Basal layer of the endometrium (C) Birth of four genetically identical babies
(D) Myometrium (D) Birth of four grotesquely deformed babies
(E) Perimetrium (E) No births

15
16 BRS Embryology

9. Embryonic carcinoma (EC) cells were isolated (D) A yellow- and black-coated offspring
from a yellow-coated mouse with a teratocarci- (E) A yellow- and white-coated offspring
noma. The EC cells were then microinjected into
the inner cell mass of a blastocyst isolated from 10. In oogenesis, which of the following events
a black-coated mouse. The blastocyst was sub- occurs immediately following the completions
sequently implanted into the uterus of a white- of meiosis II?
coated foster mouse. Which of the following (A) Degeneration of the zona pellucida
would be observed after full-term pregnancy? (B) Sperm penetration of the corona radiata
(A) A yellow-coated offspring (C) Formation of a female pronucleus
(B) A black-coated offspring (D) Appearance of the blastocyst
(C) A white-coated offspring (E) Completion of cleavage
 Answers and Explanations

1. D. Ectopic tubal pregnancy must always be an option in the diagnosis when a woman in her
reproductive years presents with such symptoms. Ninety percent of ectopic implantations occur
in the uterine tube. Ectopic tubal pregnancies result in rupture of the uterine tube and internal
hemorrhage, which presents a major threat to the woman’s life. The uterine tube and embryo
must be surgically removed. The symptoms may sometimes be confused with appendicitis.
2. C. At ovulation, a secondary oocyte begins meiosis II, but this division is arrested at metaphase.
The secondary oocyte will remain arrested in metaphase until a sperm penetrates it at fertiliza-
tion. Therefore, the term “mature ovum’” is somewhat of a misnomer because it is a secondary
oocyte that is fertilized, and, once fertilized, the new diploid cell is known as a zygote. If fertil-
ization does not occur, the secondary oocyte degenerates.
3. E. The blastocyst begins implantation by day 7 after fertilization.
4. B. The blastocyst implants in the functional layer of the uterine endometrium. The uterus is
composed of the perimetrium, myometrium, and endometrium. Two layers are identified
within the endometrium: (1) the functional layer, which is sloughed off at menstruation, and
(2) the basal layer, which is retained at menstruation and serves as the source of regeneration of
the functional layer. During the progestational phase of the menstrual cycle, the functional layer
undergoes dramatic changes; uterine glands enlarge and vascularity increases in preparation
for blastocyst implantation.
5. E. Cleavage is a series of mitotic divisions by which the large amount of zygote cytoplasm is
successively partitioned among the newly formed blastomeres. Although the number of blas-
tomeres increases during cleavage, the size of individual blastomeres decreases until they re-
semble adult cells in size.
6. B. The zona pellucida must degenerate for implantation to occur. Early cleavage states of the
blastula are surrounded by a zona pellucida, which prevents implantation in the uterine tube.
7. B. The mitochondrial DNA of all human adult cells is of maternal origin only. In human fertil-
ization, the entire sperm enters the secondary oocyte cytoplasm. However, sperm mitochondria
degenerate along with the sperm’s tail. Therefore, only mitochondria present within the second-
ary oocyte (maternal) remain in the fertilized zygote.
8. C. This scenario would result in four genetically identical children. Blastomeres at the 4- to
8-cell stage are totipotent, that is, capable of forming an entire embryo. Since blastomeres arise
by mitosis of the same cell (zygote), they are genetically identical. This phenomenon is impor-
tant in explaining monozygotic (identical) twins. About 30% of monozygotic twins arise by early
separation of blastomeres. The remaining 70% originate at the end of week 1 of development by
a splitting of the inner cell mass.
9. D. This scenario would result in a yellow- and black-coated offspring. Because EC cells and in-
ner cell mass cells have very similar biochemical characteristics, they readily mix with each
other, and development proceeds unencumbered. Because the mixture contains cells with
yellow-coat genotype and black-coat genotype, offspring with coats of two colors (yellow and
black) will be produced. The offspring are known as mosaic mice.
10. C. The secondary oocyte is arrested in metaphase of meiosis II, and it will remain in this meiotic
stage until fertilization occurs. Following fertilization, the secondary oocyte completes meio-
sis II, forming a mature ovum and a polar body. The nucleus of the mature ovum is called the
female pronucleus, which fuses with the male pronucleus to form a zygote.

17
chapter
3 Week 2 of Human
Development (Days 8–14)

I. FURTHER DEVELOPMENT OF THE EMBRYOBLAST (FIGURE 3.1)

During this period, the embryoblast differentiates into two distinct cellular layers: the dorsal epiblast
layer (columnar cells) and the ventral hypoblast layer (cuboidal cells). The epiblast and hypoblast
together form a flat, ovoid-shaped disk known as the bilaminar embryonic disk. Within the epiblast,
clefts develop and eventually coalesce to form the amniotic cavity. Hypoblast cells migrate and line
the inner surface of the cytotrophoblast to form the exocoelomic membrane, which delimits a space
called the exocoelomic cavity (or primitive yolk sac). The primitive yolk sac is later called the defini-
tive yolk sac when a portion of the exocoelomic cavity pinches off as an exocoelomic cyst. At the
future site of the mouth, hypoblast cells become columnar shaped and fuse with epiblast cells to form
a circular, midline thickening called the prochordal plate.

II. FURTHER DEVELOPMENT OF THE TROPHOBLAST

(FIGURE 3.1)
A. Syncytiotrophoblast. The syncytiotrophoblast is the outer multinucleated zone of the trophoblast
where no mitosis occurs (i.e., it arises from the cytotrophoblast). During this period, the
syncytiotrophoblast continues its invasion of the endometrium, thereby eroding endometrial
blood vessels and endometrial glands. Lacunae form within the syncytiotrophoblast and become
filled with maternal blood and glandular secretions. In addition, endometrial stromal cells
(decidual cells) at the site of implantation become filled with glycogen and lipids and also supply
nutrients to the embryoblast. The isolated lacunae fuse to form a lacunar network through which
maternal blood flows, thus establishing early uteroplacental circulation. Although a primitive
circulation is established between the uterus and future placenta, the embryoblast receives its
nutrition via diffusion only at this time.

B. Cytotrophoblast. The cytotrophoblast is mitotically active as new cytotrophoblastic cells migrate

into the syncytiotrophoblast, thereby fueling the growth of the syncytiotrophoblast. In addition,
cytotrophoblastic cells also produce local mounds called primary chorionic villi that bulge into the
surrounding syncytiotrophoblast.

18
 A B

C D

FIGURE 3.1. A. A day 8 blastocyst is shown partially implanted into the endometrium. Extraembryonic mesoderm (EEM)
has not formed yet. B. A day 12 blastocyst is shown completely implanted within the endometrium, and epithelium has
regenerated. This type of implantation is known as interstitial implantation. EEM begins to form. C. A day 13 blastocyst.
A lacunar network forms, establishing an early uteroplacental circulation. An exocoelomic cyst begins to pinch off (small
arrows). D. A day 14 blastocyst. The embryoblast can be described as two balloons (amniotic cavity and yolk sac)
pressed together at the bilaminar embryonic disk. The curved open arrow indicates that the embryoblast receives mater-
nal nutrients via diffusion. E. A sonogram at about week 3 shows a hyperechoic rim representing the chorion (thick arrow)
surrounding the chorionic cavity (or gestational sac). Within the chorionic cavity, two tiny cystic areas (i.e., the amnion
and yolk sac) separated by a thin echogenic line (i.e., embryonic disk) can be observed. Note the hyperechoic base of the
endometrium (long arrows) and two endometrial cysts (short arrows).

19
20 BRS Embryology

III. DEVELOPMENT OF EXTRAEMBRYONIC MESODERM

(FIGURE 3.1)
The extraembryonic mesoderm develops from the epiblast and consists of loosely arranged cells that
fill the space between the exocoelomic membrane and the cytotrophoblast. Large spaces develop in
the extraembryonic mesoderm and coalesce to form the extraembryonic coelom. The extraembry-
onic coelom divides the extraembryonic mesoderm into the extraembryonic somatic mesoderm and
extraembryonic visceral mesoderm.
The extraembryonic somatic mesoderm lines the trophoblast, forms the connecting stalk, and
covers the amnion. The extraembryonic visceral mesoderm covers the yolk sac. As soon as the extra-
embryonic somatic mesoderm and extraembryonic visceral mesoderm form, one can delineate the
chorion, which consists of the extraembryonic somatic mesoderm, cytotrophoblast, and syncytiotro-
phoblast. As the chorion is delineated, the extraembryonic coelom is now called the chorionic cavity.
The conceptus is suspended by the connecting stalk within the chorionic cavity.

IV. CLINICAL CONSIDERATIONS

A. Human chorionic gonadotropin (hCG) is a glycoprotein produced by the syncytiotrophoblast,
which stimulates the production of progesterone by the corpus luteum (i.e., maintains
corpus luteum function). This is clinically significant because progesterone produced by the
corpus luteum is essential for the maintenance of pregnancy until week 8. The placenta then
takes over progesterone production. hCG can be
A
assayed in maternal blood at day 8 or maternal
urine at day 10 and is the basis of pregnancy testing.
hCG is detectable throughout a pregnancy. Low
hCG values may predict a spontaneous abortion
or indicate an ectopic pregnancy. Elevated
hCG values may indicate a multiple pregnancy,
hydatidiform mole, or gestational trophoblastic
neoplasia.

B. RU-486 (mifepristone; Mifeprex) initiates menstrua-

tion when taken within 8–10 weeks of the start of the
last menstrual period. If implantation of a conceptus
has occurred, the conceptus will be sloughed along
with the endometrium. RU-486 is a progesterone-
receptor antagonist (blocker) used in conjunction
with misoprostol (Cytotec; a prostaglandin E1
[PGE1] analogue) and is 96% effective at terminating
B
pregnancy.

C. Hydatidiform mole (complete or partial; Figure 3.2)

represents an abnormal placenta characterized by
marked enlargement of chorionic villi. A complete
mole is distinguished from a partial mole by the
amount of chorionic villous involvement. The
hallmarks of a complete mole include gross,
generalized edema of chorionic villi forming
grape-like, transparent vesicles, hyperplastic
proliferation of surrounding trophoblastic cells,
and absence of an embryo/fetus. Clinical signs
diagnostic of a mole include preeclampsia during FIGURE 3.2. Hydatidiform mole.
 Chapter 3 Week 2 of Human Development (Days 8–14) 21

the first trimester, elevated hCG levels (.100,000 A

mIU/mL), and an enlarged uterus with bleeding.
About 3% to 5% of moles develop into gestational
trophoblastic neoplasia, so follow-up visits after
a mole is detected are essential. The photograph
(Figure 3.2A) shows gross edema of the chorionic
villi forming grape-like vesicles. The light
micrograph (Figure 3.2B) shows edema of the
chorionic villi (cv) surrounded by hyperplastic
trophoblastic cells (tc).

D. Gestational trophoblastic neoplasia (GTN; choriocar-

cinoma; Figure 3.3) is a malignant tumor of the
trophoblast that may occur following a normal
or ectopic pregnancy, abortion, or hydatidiform
mole. With a high degree of suspicion, elevated
hCG levels are diagnostic. Nonmetastatic GTN
(i.e., confined to the uterus) is the most common
form of the neoplasia, and treatment is highly
successful. However, the prognosis of metastatic
GTN is poor if it spreads to the liver or brain. The
photograph (Figure 3.3A) shows hemorrhagic
nodules metastatic to the liver. This is due to the B
rapid proliferation of trophoblastic cells combined
with marked propensity to invade blood vessels.
The central portion of the lesion is hemorrhagic
and necrotic, with only a thin rim of trophoblastic
cells at the periphery. The light micrograph
(Figure 3.3B) shows the distinctive alternating
arrangement of mononuclear cytotrophoblastic
cells (cy) and multinucleated syncytiotrophoblastic
cells (sy).

E. Oncofetal antigens (Table 3.1) are cell surface

antigens that normally appear only on embryonic
cells but for unknown reasons are re-expressed in
human malignant cells. Monoclonal antibodies
directed against specific oncofetal antigens provide
an avenue for cancer therapy. FIGURE 3.3. Gestational trophoblastic neoplasia.

t a b l e 3.1 Oncofetal Antigens and Tumor Markers

Antigen Associated Tumor

α-Fetoprotein (AFP) Hepatocellular carcinoma, germ cell neoplasms, yolk sac or endodermal sinus tumors
of the testicle or ovary
α-1-Antitrypsin (AAT) Hepatocellular carcinoma, yolk sac or endodermal sinus tumors of the testicle or ovary
Carcinoembryonic antigen (CEA) Colorectal cancer, pancreatic cancer, breast cancer, and small cell cancer of the lung;
bad prognostic sign if elevated preoperatively
β2-Microglobulin Multiple myeloma (excellent prognostic factor), light chains in urine (Bence Jones protein)
CA 125 Surface-derived ovarian cancer
CA 15-3 Breast cancer
CA 19-9 Pancreatic cancer (excellent marker)
Neuron-specific enolase (NSE) Small cell carcinoma of the lung, seminoma, neuroblastoma
Prostate-specific antigen (PSA) Prostate cancer
Human chorionic gonadotropin (hCG) Trophoblastic tumors, hydatidiform mole (benign), choriocarcinoma (malignant)
Bombesin Small cell carcinoma of the lung, neuroblastoma
Lactate dehydrogenase (LDH) Hodgkin disease

CA, cancer antigen.

22 BRS Embryology

Study Questions for Chapter 3

1. Which of the following components plays 6. A 16-year-old girl presents on May 10 in

the most active role in invading the endome- obvious emotional distress. On questioning, she
trium during blastocyst implantation? relates that on May 1 she experienced sexual
(A) Epiblast intercourse for the first time, without using
(B) Syncytiotrophoblast any means of birth control. Most of her anxiety
(C) Hypoblast stems from her fear of pregnancy. What should
(D) Extraembryonic somatic mesoderm the physician do to alleviate her fear?
(E) Extraembryonic visceral mesoderm (A) Prescribe diazepam and wait to see if she
misses her next menstrual period
2. Between which two layers is the extraembry- (B) Use ultrasonography to document
onic mesoderm located? pregnancy
(A) Epiblast and hypoblast (C) Order a laboratory assay for serum hCG
(B) Syncytiotrophoblast and cytotrophoblast (D) Order a laboratory assay for serum
(C) Syncytiotrophoblast and endometrium progesterone
(D) Exocoelomic membrane and (E) Prescribe diethylstilbestrol (“morning-
syncytiotrophoblast after pill”)
(E) Exocoelomic membrane and
cytotrophoblast 7. Carcinoembryonic antigen (CEA) is an on-
cofetal antigen that is generally associated with
which one of the following tumors?
3. During week 2 of development, the embryo-
blast receives its nutrients via (A) Hepatoma
(B) Germ cell tumor
(A) diffusion
(C) Squamous cell carcinoma
(B) osmosis
(D) Colorectal carcinoma
(C) reverse osmosis
(E) Teratocarcinoma
(D) fetal capillaries
(E) yolk sac nourishment
For each of Questions 8–13 concerning a
14-day-old blastocyst, select the most appropri-
4. The prochordal plate marks the site of the
ate structure in the accompanying diagram.
future
(A) umbilical cord
(B) heart
(C) mouth
(D) anus
(E) nose

5. Which of the following are components of

the definitive chorion?
(A) Extraembryonic somatic mesoderm and
epiblast
(B) Extraembryonic somatic mesoderm and
cytotrophoblast
(C) Extraembryonic somatic mesoderm and
syncytiotrophoblast
(D) Extraembryonic somatic mesoderm,
cytotrophoblast, and syncytiotrophoblast 8. Future site of the mouth
(E) Extraembryonic visceral mesoderm,
cytotrophoblast, and syncytiotrophoblast 9. Forms definitive structures found in the adult

22
 Chapter 3 Week 2 of Human Development (Days 8–14) 23

10. Chorion 15. At what location does the amniotic cavity

develop?
11. Chorionic cavity (A) Between the cytotrophoblast and
syncytiotrophoblast
12. Primary chorionic villi (B) Within the extraembryonic mesoderm
(C) Between the endoderm and mesoderm
13. Connecting stalk (D) Within the hypoblast
(E) Within the epiblast
14. A 42-year-old woman presents with com-
plaints of severe headaches, blurred vision, 16. At the end of week 2 of development
slurred speech, and loss of muscle coordina- (day 14), what is the composition of the
tion. Her last pregnancy 5 years ago resulted in embryonic disk?
a hydatidiform mole. Laboratory results show a
(A) Epiblast only
high hCG level. Which of the following condi-
(B) Epiblast and hypoblast
tions is a probable diagnosis?
(C) Ectoderm and endoderm
(A) Vasa previa (D) Ectoderm, mesoderm, and endoderm
(B) Placenta previa (E) Epiblast, mesoderm, and hypoblast
(C) Succenturiate placenta
(D) Choriocarcinoma
(E) Membranous placenta
 Answers and Explanations

1. B. The syncytiotrophoblast plays the most active role in invading the endometrium of the
mother’s uterus. During the invasion, endometrial blood vessels and endometrial glands are
eroded and a lacunar network is formed.
2. E. The extraembryonic mesoderm is derived from the epiblast and is located between the
exocoelomic membrane and the cytotrophoblast. The overall effect is to completely separate
the embryoblast from the trophoblast, with the extraembryonic mesoderm serving as a
conduit (connection) between them.
3. A. During week 2 of development, the embryoblast receives its nutrients from endometrial
blood vessels, endometrial glands, and decidual cells via diffusion. Diffusion of nutrients does
not pose a problem, given the small size of the blastocyst during week 2. Although the begin-
nings of a uteroplacental circulation are established during week 2, no blood vessels have yet
formed in the extraembryonic mesoderm to carry nutrients directly to the embryoblast (this
occurs in week 3).
4. C. The prochordal plate is a circular, midline thickening of hypoblast cells that are firmly
attached to the overlying epiblast cells. The plate will eventually develop into a membrane
called the oropharyngeal membrane at the site of the future mouth. It is interesting to note that
at this early stage of development the cranial versus caudal region of the embryo is established
by the prochordal plate, and since the prochordal plate is located in the midline, bilateral
symmetry is also established.
5. D. The definitive chorion consists of three components: extraembryonic somatic mesoderm,
cytotrophoblast, and syncytiotrophoblast. The chorion defines the chorionic cavity in which the
embryoblast is suspended and is vital in the formation of the placenta.
6. C. Human chorionic gonadotropin (hCG) can be assayed in maternal serum at day 8 of devel-
opment and in urine at day 10. If this teenager is pregnant, the blastocyst would be in week 2 of
development (day 10). Laboratory assay of hCG in either the serum or urine can be completed;
however, serum hCG might be more reliable. It is important to note that if she is pregnant, she
will not miss a menstrual period until May 15, at which time the embryo will be entering week 3
of development.
7. D. Oncofetal antigens are normally expressed during embryonic development, remain unex-
pressed in normal adult cells, but are re-expressed on transformation to malignant neoplastic
tissue. CEA is associated with colorectal carcinoma.
8. E. The prochordal plate indicates the site of the future mouth. At this early stage of develop-
ment, the orientation of the embryo in the cranial versus caudal direction is established. The
prochordal plate is a thickening of hypoblast cells that are firmly attached to the epiblast cells.
9. C. The bilaminar embryonic disk develops definitive adult structures after gastrulation occurs,
as contrasted with the trophoblast, which is involved in placental formation.
10. D. The chorion consists of three layers—extraembryonic somatic mesoderm, cytotrophoblast,
and syncytiotrophoblast. The chorion is vital in the formation of placenta.
11. G. The chorion forms the walls of the chorionic cavity in which the conceptus is suspended
by the connecting stalk. Note that the inner lining of the chorionic cavity is extraembryonic
mesoderm.
12. A. The cytotrophoblast is mitotically active, so that local mounds of cells (primary chorionic
villi) form that bulge into the surrounding syncytiotrophoblast. As development continues,

24
 Chapter 3 Week 2 of Human Development (Days 8–14) 25

primary chorionic villi form secondary chorionic villi and finally tertiary chorionic villi as part
of placental formation.
13. B. The extraembryonic mesoderm can be thought of as initially forming in a continuous layer
and then splitting as isolated cavities begin to appear everywhere except dorsally near the am-
niotic cavity and epiblast. When the isolated cavities coalesce, the extraembryonic coelom (or
chorion cavity) and connecting stalk are formed.
14. D. After a hydatidiform mole, it is very important to assure that all the invasive trophoblastic tis-
sue is removed. High levels of hCG are a good indicator of retained trophoblastic tissue because
such tissue produces this hormone. In this case, the trophoblastic tissue has developed into a
malignant choriocarcinoma and metastasized to the brain, causing her symptoms of headache,
blurred vision, and so on.
15. E. The amniotic cavity develops within the epiblast, and it is a cavity that contains the embryo
and amniotic fluid.
16. B. The embryoblast consists of the two distinct cell layers (epiblast and hypoblast) at the end of
development week 2 (day 14) and forms the bilaminar embryonic disk.
chapter
4 Embryonic Period
(Weeks 3–8)

I. GENERAL CONSIDERATIONS
A. By the end of the embryonic period, all major organ systems begin development, although
functionality may be minimal.

B. During the embryonic period, the uteroplacental circulation cannot satisfy the increasing
nutritional needs of the rapidly developing embryo, so development of the cardiovascular system
is essential.

C. During the embryonic period, folding of the embryo occurs in two distinct planes. Craniocaudal
folding progresses due to the growth of the central nervous system (CNS) and the amnion. Lateral
folding progresses due to the growth of the somites, amnion, and other components of the lateral
body wall.

D. Both the craniocaudal folding and lateral folding change the shape of the embryo from a two-
dimensional disk to a three-dimensional cylinder.

E. By the end of week 8, the embryo has a distinct human appearance.

F. During the embryonic period, the basic segmentation of the human embryo in the craniocaudal
direction is controlled by the Hox (homeobox) complex of genes.

G. The development of each individual organ system will be reviewed in forthcoming chapters.
However, it is important to realize that all organ systems develop simultaneously during the
embryonic period. In addition, embryogenesis proceeds at a slower pace in the female embryo
compared with the male embryo due to the presence of the paternally imprinted X chromosome.

II. FURTHER DEVELOPMENT OF THE EMBRYOBLAST

A. Gastrulation (Figure 4.1)
1. Gastrulation is the process that establishes the three definitive germ layers of the embryo
(ectoderm, intraembryonic mesoderm, and endoderm), forming a trilaminar embryonic disk by day
21 of development. These three germ layers give rise to all the tissues and organs of the adult.

26
 Chapter 4 Embryonic Period (Weeks 3–8) 27

Level and view of

sections A and B

A Primitive pit B
Primitive groove

Cranial Caudal
end end
Cardiogenic
area
Prochordal Cloacal
plate (future Primitive node membrane Level of
mouth) (future anus) section C
Notochord

C Caudal
Primitive groove
end

Epiblast (ectoderm)

Mesoderm Endoderm Hypoblast

FIGURE 4.1. Schematic representation of gastrulation. Embryoblast at the upper left is for orientation. A. Dorsal view of
the epiblast (blue). B. Dotted arrows (red) show the migration of cells through the primitive streak during gastrulation.
C. Cross section showing the migration of cells that will form the intraembryonic mesoderm (red) and displace the hypo-
blast (yellow) to form the endoderm. Epiblast cells migrate to the primitive streak and invaginate into a space between
the epiblast and hypoblast. Some of these migrating epiblast cells displace the hypoblast to form the definitive endoderm.
The remainder of the epiblast cells migrates laterally, cranially, and along the midline to form the definitive intraembryonic
mesoderm (e.g., cardiogenic area, notochord). After the formation of the endoderm and intraembryonic mesoderm, the
epiblast is called the definitive ectoderm.

2. Gastrulation is heralded by the formation of the primitive streak and is caused by a proliferation
of epiblast cells. The primitive streak consists of the primitive groove, primitive node, and
primitive pit.
3. As early as the bilaminar and trilaminar stages of embryogenesis, the left side/right side
(L/R) axis determination begins with the asymmetric activity of sonic hedgehog protein (Shh)
only on the future left side since Shh activity is suppressed on the future right side by
activin. In addition, the neurotransmitter serotonin (5HT) plays an important role in L/R axis
determination.
4. The cloacal membrane is the future site of the anus where the epiblast and hypoblase cells
fuse. The cloacal membrane is located caudal to the primitive streak.
5. The ectoderm, intraembryonic mesoderm, and endoderm of the trilaminar embryonic disk
are all derived from the epiblast. The term intraembryonic mesoderm describes the germ layer
that forms during week 3 (gastrulation), in contrast to the extraembryonic mesoderm, which
forms during week 2.
28 BRS Embryology

6. Intraembryonic mesoderm forms various tissues and organs found in the adult, whereas
extraembryonic mesoderm is involved in placenta formation. In this regard, later chapters do
not use the term “intraembryonic mesoderm” when discussing tissue and organ development
of the adult, but instead shorten the term to “mesoderm.”

B. Changes involving intraembryonic mesoderm (Figure 4.2)

1. Paraxial mesoderm is a thick plate of mesoderm located on each side of the midline. Paraxial
mesoderm becomes organized into segments known as somitomeres, which form in a
craniocaudal sequence. Somitomeres 1–7 do not form somites but contribute mesoderm to the
pharyngeal arches. The remaining somitomeres further condense in a craniocaudal sequence
to form 42–44 pairs of somites. The first pair of somites forms on day 20, and new somites appear
at a rate of 3 per day. The caudal-most somites eventually disappear to give a final count of
approximately 35 pairs of somites. The number of somites is one of the criteria for determining
the age of the embryo. Somites further differentiate into the following components:
a. Sclerotome forms the cartilage and bone components of the vertebral column.
b. Myotome forms epimeric and hypomeric muscles.
c. Dermatome forms dermis and subcutaneous area of skin.
2. Intermediate mesoderm is a longitudinal dorsal ridge of mesoderm located between the
paraxial mesoderm and lateral mesoderm. This ridge develops into the urogenital ridge,
which forms the future kidneys and gonads.
3. Lateral mesoderm is a thin plate of mesoderm located along the lateral sides of the embryo.
Large spaces develop in the lateral mesoderm and coalesce to form the intraembryonic
coelom. The intraembryonic coelom divides the lateral mesoderm into two layers:
a. Intraembryonic somatic mesoderm (also called somatopleure)
b. Intraembryonic visceral mesoderm (also called visceropleure or splanchnopleure)
4. Notochord is a solid cylinder of mesoderm extending in the midline of the trilaminar embryonic
disk from the primitive node to the prochordal plate. It has a number of important functions,
which include the following:
a. The notochord induces the overlying ectoderm to differentiate into neuroectoderm to form
the neural plate.
b. The notochord induces the formation of the vertebral body of each of the vertebrae.
c. The notochord forms the nucleus pulposus of each intervertebral disk.
5. Cardiogenic region is a horseshoe-shaped region of mesoderm located at the cranial end of
the trilaminar embryonic disk rostral to the prochordal plate. This region forms the future
heart.
6. Specific derivatives of mesoderm are indicated in Table 4.1.

C. Changes involving ectoderm. The major change involving a specific portion of ectoderm is its
induction by the underlying notochord to differentiate into neuroectoderm and neural crest cells,
thereby forming the future nervous system. Specific derivatives of ectoderm are indicated in Table 4.1.

D. Changes involving endoderm. Specific derivatives of endoderm are indicated in Table 4.1.

III. VASCULOGENESIS (DE NOVO BLOOD VESSEL FORMATION)

Vasculogenesis occurs in two general locations as follows.

A. In extraembryonic mesoderm:
1. Angiogenesis occurs first within extraembryonic visceral mesoderm around the yolk sac on
day 17.
2. By day 21, angiogenesis extends into extraembryonic somatic mesoderm located around
the connecting stalk to form the umbilical vessels and in secondary villi to form tertiary
chorionic villi.
 Chapter 4 Embryonic Period (Weeks 3–8) 29

Anterior Somite
A Paraxial Neural folds
Lateral folds
neuropore Posterior
mesoderm of amnion neuropore

Heart Connection Level of sections

A, B, C
with yolk sac

Endoderm Notochord
Start of
intraembryonic
coelom

Neural tube
B Somite
Intermediate
mesoderm Surface
Lateral ectoderm
mesoderm

Intraembryonic
somatic
mesodern
Endoderm

Intraembryonic Intraembryonic
coelom visceral mesoderm

Dermatome

Neural tube

Myotome

Notochord

Sclerotome

FIGURE 4.2. Schematic representation showing changes involving intraembryonic mesoderm. Picture in the upper right is
for orientation. A. Cross section at day 19. B. Cross section at day 21, with arrows indicating lateral folding of the embryo.
C. Cross section showing differentiation of the somite. Ectoderm and neuroectoderm, blue; mesoderm, red; endoderm,
yellow.
30 BRS Embryology

t a b l e 4.1 Germ Layer Derivatives

Ectoderm Mesoderm Endoderm

Epidermis, hair, nails, sweat and Muscle (smooth, cardiac, skeletal) Hepatocytes
sebaceous glands Extraocular muscles, ciliary muscle of Principal and oxyphil cells of
Utricle, semicircular ducts, vestibular eye, iris stroma, ciliary body stroma parathyroid
ganglion of CN VIII Substantia propria of cornea, corneal Thyroid follicular cells thymus
Saccule, cochlear duct (organ of endothelium, sclera, choroid Epithelial reticular cells of thymus
Corti), spiral ganglion of CN VIII Muscles of tongue (occipital somites) Acinar and islet cells of pancreas
Olfactory placode, CN I Pharyngeal arch muscles Acinar cells of submandibular and
Ameloblasts (enamel of teeth) Laryngeal cartilages sublingual glands
Adenohypophysis Connective tissue Epithelial lining of:
Lens of eye Dermis and subcutaneous layer of skin Gastrointestinal tract
Anterior epithelium of cornea Bone and cartilage Trachea, bronchii, lungs
Acinar cells of parotid gland Dura mater Biliary apparatus
Acinar cells of mammary gland Endothelium of blood and lymph vessels Urinary bladder, female urethra,
Red blood cells, white blood cells, most of male urethra
Epithelial lining of:
microglia, and Kupffer cells Inferior 2/3 of vagina
Lower anal canal
Spleen Auditory tube, middle ear cavity
Distal part of male urethra
Kidney Crypts of palatine tonsils
External auditory meatus
Adrenal cortex
Testes, epididymis, ductus deferens,
seminal vesicle, ejaculatory duct
Ovary, uterus, uterine tubes, superior
1/3 of vagina

Derivatives
Neuroectoderm
All neurons within brain and spinal cord
Retina, iris epithelium, ciliary body
epithelium, optic nerve (CN II), optic
chiasm, optic tract, dilator and
sphincter pupillae muscles
Astrocytes, oligodendrocytes,
ependymocytes, tanycytes, choroid
plexus cells
Neurohypophysis
Pineal gland
Neural Crest
Cranial neural crest cells:
Pharyngeal arch skeletal and
connective tissue components
Bones of neurocranium
Pia and arachnoid
Parafollicular (C) cells of thyroid
Aorticopulmonary septum
Odontoblasts (dentin of teeth)
Sensory ganglia of CN V, CN VII, CN
IX, CN X
Ciliary (CN III), pterygopalatine (CN
VII), submandibular (CN VII), and
otic (CN IX) parasympathetic
ganglia
Trunk neural crest cells:
Melanocytes
Schwann cells
Chromaffin cells of adrenal medulla
Dorsal root ganglia
Sympathetic chain ganglia
Prevertebral sympathetic ganglia
Enteric parasympathetic ganglia of
the gut (Meissner and Auerbach;
CN X)
Abdominal/pelvic cavity
parasympathetic ganglia

CN, cranial nerve.

 Chapter 4 Embryonic Period (Weeks 3–8) 31

3. Angiogenesis occurs by a process by which extraembryonic mesoderm differentiates into

angioblasts, which form clusters known as angiogenic cell clusters.
4. The angioblasts located at the periphery of angiogenic cell clusters give rise to endothelial
cells, which fuse with each other to form small blood vessels.

B. In intraembryonic mesoderm:
1. Blood vessels form within the embryo by the same mechanism as in extraembryonic
mesoderm.
2. Eventually, blood vessels formed in the extraembryonic mesoderm become continuous with
blood vessels within the embryo, thereby establishing a blood vascular system between the
embryo and placenta.

IV. HEMATOPOIESIS (BLOOD CELL FORMATION; FIGURE 4.3)

Hematopoiesis first occurs within the extraembryonic visceral mesoderm around the yolk sac during
week 3 of development. During this process, angioblasts within the center of angiogenic cell clusters
give rise to primitive blood cells. Beginning at week 5, hematopoiesis is taken over by a sequence of
embryonic organs: liver, thymus, spleen, and bone marrow.

V. CLINICAL CONSIDERATIONS
A. Chordoma (CD) is a benign or malignant tumor that arises from remnants of the notochord. CD
may be found either intracranially or in the sacral region and occurs more commonly in men late
in adult life (age 50 years).

B. First missed menstrual period is usually the first indication of pregnancy. Week 3 of embryonic
development coincides with the first missed menstrual period. Note that at this time the embryo has
already undergone 2 weeks of development. It is crucial that the woman become aware of a pregnancy
as soon as possible because the embryonic period is a period of high susceptibility to teratogens.

FIGURE 4.3. A schematic diagram showing the contribution of various organs to hematopoiesis during development.
During the period of yolk sac hematopoiesis, the earliest embryonic form of hemoglobin is synthesized, called he-
moglobin ξ2ε2. During the period of liver hematopoiesis, the fetal form of hemoglobin (HbF) is synthesized, called
hemoglobin α2γ2. During the period of bone marrow hematopoiesis (about week 30), the adult form of hemoglobin
(HbA) is synthesized, called hemoglobin α2β2, and gradually replaces hemoglobin α2γ2. Hemoglobin α2γ2 is the
predominant form of hemoglobin during pregnancy because it has a higher affinity for oxygen than the adult form of
hemoglobin and thereby “pulls” oxygen from the maternal blood into fetal blood.
32 BRS Embryology

C. Thalassemia syndromes are a heterogeneous group of

genetic defects characterized by the lack or decreased
synthesis of either the α-globin chain (α-thalassemia)
or β-globin chain (β-thalassemia) of hemoglobin
α2β2. α-Thalassemia is an autosomal recessive genetic
disorder most commonly caused by a deletion of the
HBA1 gene and/or the HBA2 gene on chromosome
16p13.3 for the α1-globin subunit of hemoglobin
and α2-globin subunit of hemoglobin, respectively.
β-Thalassemia is an autosomal recessive genetic
disorder caused by .200 missense or frameshift
mutations in the HBB gene on chromosome 11p15.5
for the β-globin subunit of hemoglobin.
1. Hydrops fetalis is the most severe form of α-
thalassemia and causes severe pallor, generalized
edema, and massive hepatosplenomegaly and
invariably leads to intrauterine fetal death.
2. β-Thalassemia major (Cooley anemia) is the
most severe form of β-thalassemia and causes
a severe, transfusion-dependent anemia. It is
most common in Mediterranean countries and
parts of Africa and Southeast Asia.

D. Hydroxyurea (a cytotoxic drug) promotes fetal

hemoglobin (HbF) production by the reactivation of
γ-chain synthesis. Hydroxyurea has been especially
useful in the treatment of sickle cell disease, in which FIGURE 4.4. Sacrococcygeal teratoma.
the presence of HbF counteracts the low oxygen
affinity of HbS and inhibits the sickling process.

E. Sacrococcygeal teratoma (ST; Figure 4.4) is a tumor that

arises from remnants of the primitive streak, which
normally degenerates and disappears. ST is the most
common germ cell tumor of childhood. ST is derived
from pluripotent cells of the primitive streak and often
contains various types of tissue (e.g., bone, nerve,
hair). ST occurs more commonly in female infants and
usually becomes malignant during infancy (must be
surgically removed by age 6 months). The photograph
(Figure 4.4) shows an infant with an ST.

F. Caudal dysplasia (sirenomelia; Figure 4.5) refers to

a constellation of syndromes ranging from minor
lesions of lower vertebrae to complete fusion of the
lower limbs. Caudal dysplasia is caused by abnormal
gastrulation, in which the migration of mesoderm is
disturbed. It can be associated with various cranial
anomalies:
1. VATER, which includes vertebral defects, anal
atresia, tracheoesophageal fistula, and renal
defects.
2. VACTERL, which is similar to VATER but also
includes cardiovascular defects and upper limb FIGURE 4.5. Caudal dysplasia (sirenomelia).
defects.
The photograph (Figure 4.5) shows an infant with
caudal dysplasia (sirenomelia).
 Study Questions for Chapter 4

1. Which germ layers are present at the end of (D) week 7

week 3 of development (day 21)? (E) week 8
(A) Epiblast only
(B) Epiblast and hypoblast 7. The lateral mesoderm is divided into two
(C) Ectoderm and endoderm distinct layers by the formation of the
(D) Ectoderm, mesoderm, and endoderm (A) extraembryonic coelom
(E) Epiblast, mesoderm, and hypoblast (B) intraembryonic coelom
(C) cardiogenic region
2. Which process establishes the three (D) notochord
definitive germ layers? (E) yolk sac
(A) Neurulation
(B) Gastrulation 8. Very often the first indication a woman has
(C) Craniocaudal folding that she is pregnant is a missed menstrual
(D) Lateral folding period. In which week of embryonic develop-
(E) Angiogenesis ment will a woman experience her first missed
menstrual period?
3. The first indication of gastrulation in the (A) Start of week 3
embryo is (B) Start of week 4
(A) formation of the primitive streak (C) Start of week 5
(B) formation of the notochord (D) Start of week 8
(C) formation of the neural tube (E) End of week 8
(D) formation of extraembryonic mesoderm
(E) formation of tertiary chorionic villi 9. A female newborn was found to have a large
midline tumor in the lower sacral area, which
4. Somites may differentiate into which of the was diagnosed as a sacrococcygeal tumor.
following? Which of the following courses of treatment is
recommended for this child?
(A) Urogenital ridge
(B) Kidneys (A) Immediate chemotherapy and radiation
(C) Notochord treatment
(D) Epimeric and hypomeric muscles (B) Surgical removal by age 6 months
(E) Epithelial lining of the gastrointestinal tract (C) Surgical removal at age 4–5 years
(D) Surgical removal at age 13–15 years
5. Intermediate mesoderm will give rise to the (E) No treatment because this tumor normally
regresses with age
(A) neural tube
(B) heart
10. A woman has her pregnancy suddenly
(C) kidneys and gonads
terminated due to intrauterine fetal death.
(D) somites
At autopsy, the fetus shows severe pallor, gener-
(E) notochord
alized edema, and hepatosplenomegaly. Which
of the following would you suspect?
6. The developing embryo has a distinct hu-
man appearance by the end of (A) VATER
(B) β-Thalassemia minor
(A) week 4
(C) β-Thalassemia major
(B) week 5
(D) Hydrops fetalis
(C) week 6
(E) VACTERL

33
34 BRS Embryology

11. The specialized group of mesenchy- (C) Endoderm only

mal cells that aggregate to form blood is- (D) Ectoderm and mesoderm
lands centrally and primitive blood vessels (E) Endoderm and mesoderm
peripherally are called
(A) fibroblasts 14. Which structure is derived from the same
(B) cardiac progenitor cells embryonic primordium as the dorsal root
(C) angioblasts ganglia?
(D) myoblasts (A) Gonads
(E) osteoblasts (B) Kidney
(C) Pineal gland
12. The epiblast is capable of forming which of (D) Liver
the following germ layers? (E) Adrenal medulla
(A) Ectoderm only
(B) Ectoderm and mesoderm only 15. Which structure is derived from the same
(C) Ectoderm and endoderm only embryonic primordium as the kidney?
(D) Ectoderm, mesoderm, endoderm (A) Gonads
(E) Mesoderm and endoderm only (B) Epidermis
(C) Pineal gland
13. A male newborn has a hemangioma on the (D) Liver
left frontotemporal region of his face and scalp. (E) Adrenal medulla
The cells forming the hemangioma are derived
from which of the following cell layers?
(A) Ectoderm only
(B) Mesoderm only
 Answers and Explanations

1. D. During week 3 of development, the process of gastrulation, which establishes the three pri-
mary germ layers (ectoderm, intraembryonic mesoderm, and endoderm), occurs. The origin of
all tissues and organs of the adult can be traced to one of these germ layers because these are
whence they “germinate.”
2. B. Gastrulation establishes the three primary germ layers during week 3 of development. Neu-
rulation is the process by which neuroectoderm forms the neural plate, which eventually folds
to form the neural tube.
3. A. The formation of the primitive streak on the dorsal surface of the bilaminar embryonic disk
is the first indication of gastrulation.
4. D. Approximately 35 pairs of somites form. They are derived from a specific subdivision of in-
traembryonic mesoderm called paraxial mesoderm. Somites differentiate into the components
called sclerotome (cartilage and bone of the vertebral column), myotome (epimeric and hypo-
meric muscle), and dermatome (dermis and subcutaneous area of skin).
5. C. Intermediate mesoderm is a subdivision of intraembryonic mesoderm that forms a longitu-
dinal dorsal ridge called the urogenital ridge from which the kidneys and gonads develop.
6. E. The embryo starts the embryonic period as a two-dimensional disk and ends as a three-
dimensional cylinder. This dramatic change in geometry is caused by formation of all the
major organ systems. As the organ systems gradually develop during the embryonic period,
the embryo appears more and more human-like; it has a distinct human appearance at the
end of week 8.
7. B. The lateral mesoderm is a subdivision of intraembryonic mesoderm and initially is a solid
plate of mesoderm. The intraembryonic coelom forms in the middle of the lateral mesoderm,
thereby dividing it into the intraembryonic somatic mesoderm and intraembryonic visceral
mesoderm.
8. A. Given a regular 28-day menstrual cycle, a woman who starts menses on, say, February 1 will
ovulate on February 14, and the secondary oocyte will be fertilized, if she becomes pregnant,
within 24 hours. So, the zygote undergoes week 1 of development from February 15 to 21. Week
2 of development is from February 22 to 28. On the next day, March 1, the woman would enter
her next menstrual cycle if she were not pregnant, but because she is pregnant, she does not
menstruate. Therefore, this first missed menstrual period corresponds with the start of week 3
of embryonic development. The embryonic period (week 3–week 8) is a time of high suscepti-
bility to teratogens.
9. B. The preponderance of sacrococcygeal tumors is found in female newborns. Because these
tumors develop from pluripotent cells of primitive streak origin, malignancy is of great concern,
and the tumor should be surgically removed by age 6 months. Occasionally, these tumors may
recur after surgery, demonstrating malignant properties.
10. D. Hydrops fetalis is the most severe form of α-thalassemia, and is a direct result of the lack or
decreased synthesis of the α-globin chain of hemoglobin α2β2.
11. B. The angioblasts are the mesenchymal cells that form blood vessels in embryonic develop-
ment, as well as embryonic blood cells.
12. D. The epiblast is capable of forming all three germ layers (ectoderm, mesoderm, and endo-
derm) during gastrulation. Epiblast cells migrate to the primitive streak and invaginate into a
space between the epiblast and hypoblast. Some of these epiblast cells displace the hypoblast to

35
Other documents randomly have
different content
therefore am I now come. As thou dost hunt this stag; even so will I
hunt thee.”
Placidus swooned at these words, and fell from his horse. How
long he lay on the ground he knew not. When his senses returned, he
cried in anguish:
“Tell me thy will, O Lord, that I may believe in thee, and perform
it.”
Then replied the voice: “I am Christ, the son of the living God. I
created heaven and earth, caused the light to arise, and divided it
from the darkness. I appointed days, and seasons, and years. I
formed man out of the dust of the earth, and for his sake took upon
me his form. Crucified, and buried, on the third day I arose again.”
“All this I believe, Lord,” replied Placidus; “yea, and that thou art
he who bringest back the wandering sinner.”
Then said the voice: “If thou believest, go into the city and be
baptized.”
“Shall I reveal this unto my wife and children, Lord, that they also
may believe?”
“Yea,” replied the voice; “return here on the morrow’s dawn, that
thou mayest know of thy future life.”
Placidus returned to his wife, and told her all that had happened
unto him; then did they believe, and were baptized, and their
children with them. The knight was called Eustace, his wife
Theosbyta, whilst to his two sons the names of Theosbytus and
Agapetus were given in their baptism. On the morrow, the knight
returned to the place where he had seen the vision.
“I implore thee, O Lord, to manifest thyself according to thy word,”
prayed the knight.
Then the voice was heard, saying: “Blessed art thou, Eustace, in
that thou hast been washed with the laver of my grace, and thereby
overcome the Devil. Now hast thou trodden him to dust, who
beguiled thee. Now will thy fidelity be shown; for he whom thou hast
forsaken will rage continually against thee. Many things must thou
undergo for my sake. Thou must become another Job; fear not;
persevere; my grace is sufficient for thee. In the end thou shalt
conquer; choose then, whether thou wilt experience thy trials in
thine old age, or forthwith.”
 “Even as thou willest, O Lord; yet, if it may be so, try me now, and
help me in my trial.”
“Be bold, Eustace; my grace can support you.” With these words,
the voice died away, and was no more heard; and Eustace, after
prayer and praise to God, rose from his knees, and returned to his
own house.
But a few days had elapsed, ere the trials of Job came upon
Eustace and his family; pestilence carried off his flocks and his herds,
and his servants fled away, or died with their charges. Robbers
plundered his palace, driving away the knight, his wife, and his sons,
in poverty and nakedness. It was in vain that the emperor sought
everywhere for the knight, for not the slightest trace of him could be
found.
At length the unhappy fugitives, covered with such rags as they
could obtain, reached the sea-shore, and besought a passage across
the waters. The captain of the vessel was captivated with the beauty
of Theosbyta, and consented to carry them over. No sooner were they
on the further side, than he demanded of them money for their
voyage.
“Good master,” said Eustace, “I am poor and destitute, and have
no money.”
“Very well,” replied the captain; “thy wife will do as well; I take her
as my slave; she will sell for the passage money.”
“With my life only will I part with her,” exclaimed the knight, as
his wife clung to him in her distress.
“As you please, master; ho, men! seize the woman, and take her to
my cabin; as for the man and his brats, heave them overboard.”
“Leave me, leave me, Eustace,” murmured Theosbyta; “save thyself
and our children; I can but die once.”
With many a hard struggle, Eustace consented; he clasped his two
boys by their hands, and led them from the ship.
“Ah, my poor children!” he cried; “your poor mother is lost; in a
strange land and in the power of a strange lord must she lament her
fate.”
A few hours’ travelling brought Eustace and his children to the
bank of a broad and rapid river, the water of which ran so deep, that
he feared to cross its stream with both his boys at one time; placing
one therefore on the bank, under the shade of a bush, he clasped the
eldest in his arms and plunged into the river. The stream ran swiftly,
and the bottom was treacherous; but at length he reached the further
side, and placed Theosbytus on the bank. Again he plunged into the
river. The middle of the stream was but fairly gained, when he saw a
wolf creep from the wood close to which his younger son was placed,
and approach the child. It was all in vain that he shouted, and strove
to reach the shore; the wolf seized the child and bore it off, before its
father’s eyes. At that moment a loud roar from the other bank
startled the bereaved father; he turned, and saw a lion carrying away
his eldest son.
“Alas, alas!” exclaimed Eustace, as soon as he had reached the
further bank of the river. “Once was I flourishing like a luxuriant
tree, but now I am altogether blighted. Military ensigns were around
me, and bands of armed men. Now I am alone in the world. My wife,
my children are taken from me; the one to slavery, the others to
death. O Lord, thou didst warn me that I must endure the perils of
Job, are not these worse than that holy man’s? In his greatest misery
he had a couch whereon to rest his wearied limbs, and friends to
compassionate him in his misfortunes. His wife, too, remained to
him—mine is gone from me: place a bridle on my lips, lest I utter
foolishness, and stand up against thee, O my God.”
His heart relieved by these passionate expressions, the knight
continued his travel; after many days of want and fatigue, he reached
a far-off village, where he abode with one of the villagers as his hired
servant. For fifteen years he served his master faithfully, and at his
death he succeeded to his cottage and his land.
Trajan still lived, but his fortunes did not prosper; his enemies
became daily stronger and stronger, for Placidus no longer directed
the movements of the imperial army, or urged on the soldiers, by his
example, to deeds of valor against the enemy. Often and often did the
emperor think of his lost commander, and ceaseless were his
endeavors to discover the place of his concealment.
Eustace was working in his fields about this time, little thinking of
Trajan, or of Rome, when two men drew near, and after observing
him for some time, and communing with each other, accosted the
knight.
 “Friend,” said one of the men, “dost know in these parts a knight
named Placidus and his two sons?”
The heart of Eustace was sore tried, when he saw the emissaries of
Trajan. The sight of them recalled his previous honors in the world,
and he still felt a lingering wish to retrace his steps. “Nay,” he
thought, “were I not alone, it were well to return; but for a solitary,
this place is best.” Then said he to the two men:
“There is no one about here, good sirs, of the name you ask after.”
“It is but a fool’s errand we are on, master, I fear,” said the man;
“we have travelled far and near after our old general, but no one
knows aught of him.”
“It is years since he left Rome, friends, is it not?” rejoined Eustace.
“Fifteen years and more; but come, comrade, we must go
onwards.”
“Nay, sirs, come to my poor abode; what I have is at your service.”
The emissaries of Trajan gladly acceded to Eustace’s request. The
homely repast was soon placed on the board, and the men sat down
to refresh themselves, while Eustace waited upon them. Again the
thoughts of his old home came thickly upon him, and he could not
restrain his tears. He left the room where his guests were, bathed his
face with water, and returned to wait on the two men.
“I have a strange presentiment,” remarked one of the men during
Eustace’s absence, “that our good host is even he whom we search
after. Marked you not how he hesitated when we first addressed
him?”
“Ay, and even now he has left us with his eyes red with suppressed
tears.”
“Let us try the last test, the sabre mark on his head, which he
received in the passage of the Danube, when he struck down the
northern champion.”
As soon as Eustace returned the soldiers examined his head, and
finding the wished-for mark, embraced their old general; the
neighbors, too, came in, and the exploits of Eustace were soon in the
mouths of the villagers.
For fifteen days they journeyed towards Rome, Eustace and his
two guides; as they neared the imperial capital, the emperor came
out to meet his old commander. Eustace would have fallen at his
master’s feet, but Trajan forbade him; and side by side, amid the
congratulations and applauses of the people, the emperor and his
long-lost servant entered Rome.
The return of Eustace inspired the people with confidence;
thousands hurried from every village to volunteer as soldiers, and his
only difficulty was to select who should be rejected. One contingent
from a far-off village arrested his attention; it was headed by two
youths of wonderful likeness the one to the other, and apparently
within a year of the same age. They were tall in stature, of
commanding features, and their selection as leaders, by their
comrades, did justice to their attainments and the superiority of their
manners. Pleased with the youths, Eustace placed them in the van of
his army, and began his march against the invaders, who had
reached within a few miles of the coast whereon he had disembarked
from the ship of the barbarous captain.
Pitching his camp within sight of that of the enemy, the
commander billeted the best of his troops in a small village that
formed the rear of his position. A widow lady, of but few years, but
sorely worn with grief, received the two youths into her house. About
the mid-day meal, the youths conversed the one with the other of
their early life.
“Of what I was when a child,” said the elder, “I know only this, that
my father carried me over a broad river, and laid me under a bush
whilst he returned to fetch my brother; but whilst he was gone a lion
came, seized me by the clothes, and bore me into a wood hard by. My
mother we lost on our journey nigh to a great sea, where she
remained with a cruel captain who had seized her for his slave. As I
was carried away by the lion, methought a wolf seized on my brother,
whom my father had left on the other bank. The lion soon dropped
me, for men with loud cries and stones pursued him and drove him
from me. Then did they take me to the village where we have lived
together so long.”
“My brother, O my brother!” exclaimed the other youth, hardly
able to restrain his emotions during the recital, “I am he whom the
wolf carried off, saved from his jaws by the shepherds, as thou wast
from the jaws of the lion.”
 The widow had listened to the wonderful story of the two young
men. Much she marvelled at their preservation; on the morrow she
sought the commander of the imperial forces; she found him in his
tent; his officers were around him, and the two young men stood
within the circle. The widow craved permission to return to her own
country.
“Sir,” she said, “I am a stranger in these parts; fifteen years have
passed since I left Rome with my husband, once high in power, and
rich, but then poor and in misery; we reached yonder sea, our two
sons were with us, we crossed in a shipman’s boat, but when we
arrived on this side he demanded money of my husband, and when
he had it not to give him he seized on me and carried me into slavery.
Years lived I beneath his roof in sorrow and in pain; but it was in
vain that he sought to do me evil, for God preserved me from his
devices. At length my master died, and I became free; since then I
have labored honestly, and would now return to Rome, if, perchance,
I may find my husband and my children.”
“Theosbyta!” said the general, in a low voice, raising his helmet as
he spoke.
“Eustace! my husband!”
The general raised his fainting wife, and kissed her gently on her
forehead. “Our sons, Theosbyta, we shall see no more; a lion and a
wolf carried them off before mine eyes, as we crossed the river not
many leagues from hence.”
“Father! our father!” said the two youths, as they knelt before the
general.
“Nay, doubt not, Eustace,” said his wife, “last night I overheard the
tale of their adventures; this is he whom the lion took; this one did
the shepherds rescue from the jaws of the wolf.”
The tale was soon retold, and Eustace convinced that he had
recovered in one day his wife and his sons. Then loud blew the
trumpets through the camp, and cheer upon cheer rang from the
good soldiers, when their general came from his tent, leading his
long-lost wife, and supported on either side by his sons. The
enthusiasm aided them in obtaining the victory over the enemy.
Every one loved their general, and rejoiced in his joy; and that day
they fought for their home, their emperor, and their commander.
 Trajan lived not to welcome home his honored general; his
successor, however, spared not to receive Eustace with the honors
his achievements deserved. The banquet-hall was gorgeous with
ornaments; and the banquet replete with delicacies and curiosities.
On the emperor’s right hand sat Eustace, and his sons occupied no
mean place in the banquet-hall.
“To-morrow,” said the emperor, “we will sacrifice to the great gods
of war, and offer our thanks for this thy victory.”
“As my lord pleases,” said Eustace; “one thing I pray, that my lord
will not regard my absence from the temple as an intentional slight
on his royal person.”
“Absence, sir!” exclaimed the emperor; “I command your
attendance; see that you and yours are before the altar of Mars at
noon to-morrow; thou shalt offer there with thine own hands.”
“I will cut off the hand that so offends,” replied Eustace.
“Ah! a Christian—be it so—sacrifice or die!”
“Death then, my lord; I worship Christ, not idols.”
“Let him save thee from the lions’ mouths,” exclaimed the impious
emperor. “Ho, guards! this Christian and his sons to the beasts’ den;
come, my guests, to the arena.”
“And me to my lord,” said Theosbyta, advancing from the lower
part of the hall.
“As thou wilt: come, sirs; our lions will be well fed.”
The party reached the amphitheatre; it was crowded with
spectators. Rumor had soon carried abroad the tidings that the
triumphant general was to die by the lion’s mouth, for his
Christianity. Some pitied him for what they called his folly: “What,
die for a little incense thrown on the fire!” Others gloried in his
expected death, for they hated the new faith. A few in secret prayed
to God, to give their brother strength to undergo his fearful
martyrdom, for they were Christians.
Eustace stood in the arena; his wife knelt by his side, his sons
stood before him to meet the lion’s first bound. The crowd grew
impatient—a sudden silence; a sound as of revolving hinges, and
then a sullen roar, as with a bound the lion sprang into the centre of
the amphitheatre. One look he cast on the youths; and then he bowed
his head, crept to their feet and licked them; another, and another,
was let loose; but the old lion kept guard over the family, and fought
with the other lions, and drove them back to their dens.
“It is enough,” said the emperor, “he has a charm against the teeth
of beasts; we will test his powers against the heat of fire; prepare the
brazen ox.”
A fire was lighted beneath the animal, a vast hollow frame that
represented an ox, and into the belly of which the victims were
introduced through a door in the right side. As soon as it was heated
to its utmost heat, the executioners hastened to throw their victims
in; Eustace forbade them, and then clasping his wife in his arms, and
followed by his sons, he moved slowly up the ladder that led to the
horrid cell, and entered the belly of the brazen ox calmly and without
fear.
For three days the fire was kept burning beneath the creature. On
the third evening the beast was opened; within lay Eustace, his wife,
and his sons, as it were in a deep and placid sleep. Not a hair of their
heads was burnt, nor was the smell of fire upon their persons.
So died they all: the father, the wife, and the children. The people
buried them with honor, and remembered with sorrow the
martyrdom of the Christian general.
“The scene of the conversion,” said Thompson, “recalls to my mind Doddridge’s
account of Colonel Gardiner, converted from his licentious life by an almost similar
vision of our Saviour on the cross, and by an address not less effective than the
words heard by the Eustace of your tale.”
“Few of my old monk’s tales are more true, in their leading features,” said
Herbert, “than this of the trials of Eustace and his family. It has been told more
than once as an authentic history, and you will find it alluded to in Butler’s ‘Lives
of the Saints,’ where it is stated that a church at Rome was dedicated to the
memory of St. Eustachius.”
“Surely the incident of the stag and the cross is very similar to that in the legend
of St. Herbert.”
“Almost identical, Thompson,” rejoined Herbert; “in the foreign pictures the two
incidents are generally depicted in nearly the same manner.”
“Another curious similarity occurs in the early English romance of Sir
Isumbras,” said Lathom. “That knight’s misfortunes came upon him in a very
similar manner to poor Eustace’s: the knight, his wife, and his three children
wander on their pilgrimage to the Holy Land; she wrapped in his surcoat, his
scarlet mantle being divided among his three children. They so reach a river, and
two of their children are carried off by a lion and a leopard ; one child, however,
and the mother are left: then sings the old poet:

“‘Through the forest they went days three,

Till they came to the Greekish sea;
They grieved and were full wo!
As they stood upon the land
They saw a fleet come sailand (sailing),
Three hundred ships and mo. (more),
With top castles set on loft,
Richly then were they wrought,
With joy and mickle pride:
A heathen king was therein,
That Christendom came to win,
His power was full wide.’”

“The king, of course, plays the part of the cruel ship-captain,” said Herbert.
“Yes. Seven days’ hunger drives the knight and his lady to the sultan’s galley, to
ask for bread: taken for spies, they are at first driven off, until the noble stature of
the knight, and the fair complexion of the wife, ‘bright as a blossom on a tree,’
convince the Saracens that their piteous tale is true. To the knight the sultan offers
rank, honors, and wealth, if he will renounce Christianity and fight under the
Moslem banners. Sir Isumbras refuses, and renews his petition for bread. Then,
continues the poet,

“‘The sultan beheld that lady there,

Him thought an angel that she were,
Comen a-down from heaven:
Man—I will give thee gold and fee,
An thou that woman will sellen me,
More than thou can never (name).
I will give thee a hundred pounds
Of pennies that be whole and round,
And rich robes seven.
She shall be queen of my land;
And all men bow unto her hand;
And none withstand her steven (voice).
Sir Isumbras said—Nay;
My wife I will not sell away,
Though ye me for her sloo (slew).
I wedded her in goddis lay
To hold her to my ending day,
Both for weal and wo.’”

“A decided refusal to complete the bargain,” said Thompson.

 “Yet not so taken by the sultan; the money is counted into the knight’s cloak, the
lady taken forcible possession of, and Sir Isumbras and his child carried on shore,
and beat until hardly able to move, but here we must stop with the early English
romance, having already gone beyond its similarity to the old monk’s story. And
now I must break off for to-night; I know it is but a short allowance, and shall be
compensated for when we next meet.”
 CHAPTER XI.

Another Chat about Witches and Witchcraft—Late Period of the Existence of

Belief in Witches—Queen Semiramis—Elfin Armorers—The Sword of the
Scandinavian King—Mystical Meaning of Tales of Magic—Anglo-Saxon
Enigmas—Celestinus and the Miller’s Horse—The Emperor Conrad
and the Count’s Son—Legend of “The Giant with the Golden Hairs.”

“Y our stories about sorcerers and sorcery, Lathom,” said Herbert, “have made
me consider a little as to the amount of truth on which such fictions may
have been founded.”
“Perhaps you believe in witches, magicians, and all that tribe, that gather deadly
herbs by moonlight, and ride through the air on broomsticks,” said Thompson,
with a smile.
“May not Herbert fairly ask you,” said Lathom, “whether there is any antecedent
improbability in mortal beings obtaining, from the spirit of evil, a temporary
superhuman power; or in the idea of Satan awarding the riches and honors of this
world to those who will fall down and worship him?”
“Selden’s apology for the law against witches in his time shows a lurking belief,”
remarked Herbert. “‘If,’ says that sour old lawyer, ‘one man believes that by
turning his hat thrice and crying “buz,” he could take away a fellow-creature’s life,
this were a just law made by the state, that whosoever should do so, should forfeit
his life.’”
“He must have believed, or his logical mind would have seen, that a law waging
war with intentions which are incapable of fulfilment, is both wrong and
mischievous.”
“Well,” said Herbert, “as good a lawyer as Selden and a better man, did not fear
to profess his belief in witchcraft, and to give his judicial countenance to trials for
sorcery:—Sir Matthew Hale was ever ready to admit his belief in witches and
witchcraft.”
“To the lawyers you may add the learned antiquary and physician, Sir Thomas
Brown, the author of the ‘Religio Medici.’”
“But surely, Lathom, all this belief, as well as the practice of witch-tormenting,
ceased about 1682,” said Thompson.
 “The belief in witchcraft has never yet been extinct, and the practice of witch-
burning lasted forty years after that, at least in Scotland. The act of James, so
minutely describing witches and their acts, and so strenuously inciting the people
to burn them, remained on the statute-book until the ninth year of George the
Second; and as late as 1722 the hereditary sheriff of Sutherlandshire condemned a
poor woman to death as a witch.”
“I believe I can carry down the belief at least a few years later than the date even
of the last witch execution,” remarked Herbert.
“Among the poor and uneducated, undoubtedly?”
“Nay, Thompson, with them it remains even now; I speak not only of the
educated, but of that class of men which is most conversant with evidence, and
most addicted to discredit fictitious stories.”
“What, the lawyers?”
“Even so,” replied Lathom; “in 1730, William Forbes, in his ‘Institutes of the Law
of Scotland,’ published in that year, makes this remark: ‘Nothing seems plainer to
me, than that there have been witches, and that, perhaps, such are now actually
existing; which I intend, God willing, to clear in a larger work concerning the
criminal law.’”
“Did this large work appear?” said Thompson.
“I should think not; at least, it is not known.”
“The old Jesuit from whom you got your version of The Ungrateful Man, has a
story illustrative of a kind of witchcraft that all will admit to have been very
prevalent in every age,” said Thompson.
“What, will you believe in witchcraft in any form?”
“At all events, in one form—the witchcraft of love; my instance is the story of
Semiramis and Ninus. I will read it you from the same version that Lathom used
for his tale of Vitalis and Massaccio.”
 THE QUEEN SEMIRAMIS.
“Of all my wives,” said King Ninus to Semiramis, “it is you I love
the best. None have charms and graces like you, and for you I would
willingly resign them all.”
“Let the king consider well what he says,” replied Semiramis.
“What if I were to take him at his word?”
“Do so,” returned the monarch; “whilst beloved by you, I am
indifferent to all others.”
“So, then, if I asked it,” said Semiramis, “you would banish all your
other wives, and love me alone? I should be alone your consort, the
partaker of your power, and queen of Assyria?”
“Queen of Assyria! Are you not so already,” said Ninus, “since you
reign, by your beauty, over its king?”
“No—no,” answered his lovely mistress; “I am at present only a
slave whom you love. I reign not; I merely charm. When I give an
order, you are consulted before I am obeyed.”
“And to reign, then, you think so great a pleasure?”
“Yes, to one who has never experienced it.”
“And do you wish, then, to experience it? Would you like to reign a
few days in my place?”
“Take care, O king! do not offer too much.”
“No, I repeat it,” said the captivated monarch. “Would you like, for
one whole day, to be sovereign mistress of Assyria? If you would, I
consent to it.”
“And all which I command, then, shall be executed?”
“Yes, I will resign to you, for one entire day, my power and my
golden sceptre.”
“And when shall this be?”
“To-morrow if you like.”
“I do,” said Semiramis; and let her head fall upon the shoulder of
the king, like a beautiful woman asking pardon for some caprice
which has been yielded to.
The next morning, Semiramis called her women, and commanded
them to dress her magnificently. On her head she wore a crown of
precious stones, and appeared thus before Ninus. Ninus, enchanted
with her beauty, ordered the officers of the palace to assemble in the
state chamber, and his golden sceptre to be brought from the
treasury. He then entered the chamber, leading Semiramis by the
hand. All prostrated themselves before the aspect of the king, who
conducted Semiramis to the throne, and seated her upon it. Then
ordering the whole assembly to rise, he announced to the court that
they were to obey, during the whole day, Semiramis as himself. So
saying, he took up the golden sceptre, and placing it in the hands of
Semiramis—“Queen,” said he, “I commit to you the emblem of
sovereign power; take it, and command with sovereign authority. All
here are your slaves, and I myself am nothing more than your
servant for the whole of this day. Whoever shall be remiss in
executing your orders, let him be punished as if he had disobeyed the
commands of the king.”
Having thus spoken, the king knelt down before Semiramis, who
gave him, with a smile, her hand to kiss. The courtiers then passed in
succession, each making oath to execute blindly the orders of
Semiramis. When the ceremony was finished, the king made her his
compliments, and asked her how she had managed to go through it
with so grave and majestical an air.
“Whilst they were promising to obey me,” said Semiramis, “I was
thinking what I should command each of them to do. I have but one
day of power, and I will employ it well.”
The king laughed at this reply. Semiramis appeared more piquante
and amiable than ever. “Let us see,” said he, “how you will continue
your part. By what orders will you begin?”
“Let the secretary of the king approach my throne,” said
Semiramis, in a loud voice.
The secretary approached; two slaves placed a little table before
him.
“Write,” said Semiramis: “‘Under penalty of death, the governor of
the citadel of Babylon is ordered to yield up the command of the
citadel to him who shall bear to him this order.’ Fold this order, seal
it with the king’s seal, and give it to me. Write now: ‘Under penalty of
death, the governor of the slaves of the palace is ordered to resign the
command of the slaves into the hands of the person who shall
present to him this order.’ Fold, seal it with the king’s seal, and
deliver to me this decree. Write again: ‘Under penalty of death, the
general of the army encamped under the walls of Babylon is ordered
to resign the command of the army to him who shall be the bearer of
this order.’ Fold, seal, and deliver to me this decree.”
She took the three orders, thus dictated, and put them in her
bosom. The whole court was struck with consternation; the king
himself was surprised.
“Listen,” said Semiramis. “In two hours hence let all the officers of
the state come and offer me presents, as is the custom on the
accession of new princes, and let a festival be prepared for this
evening. Now, let all depart. Let my faithful servant Ninus alone
remain. I have to consult him upon affairs of state.”
When all the rest had gone out—“You see,” said Semiramis, “that I
know how to play the queen.”
Ninus laughed.
“My beautiful queen,” said he, “you play your part with
astonishment. But, if your servant may dare question you, what
would you do with the orders you have dictated?”
“I should be no longer queen were I obliged to give an account of
my actions. Nevertheless, this was my motive. I have a vengeance to
execute against the three officers whom these orders menace.”
“Vengeance—and wherefore?”
“The first, the governor of the citadel, is one-eyed, and frightens
me every time I meet him; the second, the chief of the slaves, I hate,
because he threatens me with rivals; the third, the general of the
army, deprives me too often of your company,—you are constantly in
the camp.”
This reply, in which caprice and flattery were mingled, enchanted
Ninus. “Good,” said he, laughing. “Here are the three first officers of
the empire dismissed for very sufficient reasons.”
The gentlemen of the court now came to present their gifts to the
queen. Some gave precious stones; others, of a lower rank, flowers
and fruits; and the slaves, having nothing to give, gave nothing but
homage. Among these last, there were three young brothers, who had
come from the Caucasus with Semiramis, and had rescued the
caravan in which the women were, from an enormous tiger. When
they passed before the throne—
“And you,” said she to the three brothers, “have you no present to
make to your queen?”
“No other,” replied the first, Zopire, “than my life to defend her.”
“None other,” replied the second, Artaban, “than my sabre against
her enemies.”
“None other,” replied the third, Assar, “than the respect and
admiration which her presence inspires.”
“Slaves,” said Semiramis, “it is you who have made me the most
valuable present of the whole court, and I will not be ungrateful. You
who have offered me your sword against my enemies, take this order,
carry it to the general of the army encamped under the walls of
Babylon, give it to him, and see what he will do for you. You who
have offered me your life for my defence, take this order to the
governor of the citadel, and see what he will do for you; and you who
offer me the respect and admiration which my presence inspires,
take this order, give it to the commandant of the slaves of the palace,
and see what will be the result.”
Never had Semiramis displayed so much gayety, so much folly,
and so much grace, and never was Ninus so captivated. Nor were her
charms lessened in his eyes, when a slave not having executed
promptly an insignificant order, she commanded his head to be
struck off, which was immediately done.
Without bestowing a thought on this trivial matter, Ninus
continued to converse with Semiramis till the evening and the fête
arrived. When she entered the saloon which had been prepared for
the occasion, a slave brought her a plate, in which was the head of
the decapitated eunuch.—“’Tis well,” said she, after having examined
it. “Place it on a stake in the court of the palace, that all may see it,
and be you there on the spot to proclaim to every one, that the man
to whom this head belonged lived three hours ago, but that having
disobeyed my will, his head was separated from his body.”
The fête was magnificent; a sumptuous banquet was prepared in
the gardens, and Semiramis received the homage of all with a grace
and majesty perfectly regal; she continually turned to and conversed
with Ninus, rendering him the most distinguished honor. “You are,”
said she, “a foreign king, come to visit me in my palace. I must make
your visit agreeable to you.”
Shortly after the banquet was served, Semiramis confounded and
reversed all ranks. Ninus was placed at the bottom of the table. He
was the first to laugh at this caprice; and the court, following his
example, allowed themselves to be placed, without murmuring,
according to the will of the queen. She seated near herself the three
brothers from the Caucasus.
“Are my orders executed?” she demanded of them.
“Yes,” replied they.
The fête was very gay. A slave having, by the force of habit, served
the king first, Semiramis had him beaten with rods. His cries
mingled with the laughter of the guests. Every one was inclined to
merriment. It was a comedy, in which each played his part. Towards
the end of the repast, when wine had added to the general gayety,
Semiramis rose from her elevated seat, and said: “My lords, the
treasurer of the empire has read me a list of those who this morning
have brought me their gifts of congratulation on my joyful accession
to the throne. One grandee alone of the court has failed to bring his
gift.”
“Who is it?” cried Ninus. “He must be punished severely.”
“It is yourself, my lord—you who speak; what have you given to the
queen this morning?”
Ninus rose, and came with a smiling countenance to whisper
something into the ear of the queen. “The queen is insulted by her
servant!” exclaimed Semiramis.
“I embrace your knees to obtain my pardon, beautiful queen,” said
he; “pardon me, pardon me”; and he added in a lower tone, “I wish
this fête were finished.”
“You wish, then, that I should abdicate?” said Semiramis. “But no
—I have still two hours to reign”; and at the same time she withdrew
her hand, which the king was covering with kisses. “I pardon not,”
said she, with a loud voice, “such an insult on the part of a slave.
Slave, prepare thyself to die.”
 “Silly child that thou art,” said Ninus, still on his knees, “yet will I
give way to thy folly; but patience, thy reign will soon be over.”
“You will not then be angry,” said she, in a whisper, “at some thing
I am going to order at this moment.”
“No,” said he.
“Slaves!” said she aloud, “seize this man—seize this Ninus!”
Ninus, smiling, put himself into the hands of the slaves.
“Take him out of the saloon, lead him into the court of the seraglio,
prepare every thing for his death, and wait my orders.”
The slaves obeyed, and Ninus followed them, laughing, into the
court of the seraglio. They passed by the head of the disobeying
eunuch. Then Semiramis placed herself on a balcony. Ninus had
suffered his hands to be tied.
“Hasten,” said the queen, “hasten, Zopire, to the fortress; you to
the camp, Artaban; Assar, do you secure all the gates of the palace.”
The orders were given in a whisper, and executed immediately.
“Beautiful queen,” said Ninus, laughing, “this comedy wants but its
conclusion; pray, let it be a prompt one.”
“I will,” said Semiramis. “Slaves, recollect the eunuch. Strike!”
They struck; Ninus had hardly time to utter a cry; when his head
fell upon the pavement, the smile was still upon his lips.
“Now, I am queen of Assyria,” exclaimed Semiramis; “and perish
every one, like the eunuch and Ninus, who dare disobey my orders.”
“The discovery of the sword by Sir Guido, in your tale of the Crusader,” said
Herbert, “reminds me of the elfin swords so common among the Scandinavian
heroes.”
“Such as the enchanted sword taken by a pirate from the tomb of a Norwegian
monarch,” suggested Lathom.
“Rather, perhaps, of those manufactured by the elves under compulsion, or from
gratitude to some earthly warrior; the famous sword Tyrfing, the weapon of the
Scandinavian monarch Suafurlami, was one of these. This is the story as given by
Scott, in the second volume of his Scottish Minstrelsy: ‘The Scandinavian king,
returning from hunting, bewildered himself among the mountains; about sunset he
beheld a large rock, and two dwarfs sitting before the mouth of a cavern. The king
drew his sword, and intercepted their retreat by springing between them and their
recess, and imposed upon them the following condition of safety:—That they
should make him a falchion, with a baldric and scabbard of pure gold, and a blade
which would divide stones and iron as a garment, and which would render the
wielder of it ever victorious in battle. The elves complied with his demand, and
Suafurlami pursued his way home. Returning at the time appointed, the dwarfs
delivered to him the famous sword Tyrfing; then standing in the entrance to the
cavern, spoke thus: “This sword, O king, shall destroy a man every time it is
brandished; but it shall perform three atrocious deeds, and shall be thy bane.” The
king rushed forward with the charmed sword, and buried both its edges in the
rock, but the dwarfs escaped into their recesses. This enchanted sword emitted
rays like the sun, dazzling all against whom it was brandished; it divided steel like
water, and was never unsheathed without slaying a man.’”
“The supernatural skill in the fabrication of arms attributed to the Northern
elves,” remarked Lathom, “seems to indicate some traces of historical truth. The
Fins, who inhabited Scandinavia when Odin and his Asiatics invaded the country,
retired to the mountains to avoid the tyranny of the new people. Far better
acquainted than the invaders could have been with the mines of their country, a
superior knowledge in the manufacture of arms may be fairly awarded to them.
And thus, in time, the oppressed Fins would come to be the dwarfish armorers of
Scandinavian mythology.”
“As theory is the fashion,” said Thompson, “what say you to a geological
foundation to many of your mythological wonders? Were not the great dragons of
stone suddenly released from their rocky beds—the long serpents guarding
treasures in deep pits—the closely coiled snake of the cavern—were not many of
these the gigantic antediluvian relics of our caves? Has not many an ichthyosaurus,
in his earthly bed, been transformed into a deputy fiend, or even into the father of
evil himself, keeping watch over some hoard of ill-gotten wealth; whilst the strange
form of the huge pterodactyl, with its wings and claws, has been metamorphosed
into the dragon of Wantley and his compeers?”
“Your theory, Thompson,” rejoined Herbert, “may not be so baseless as you
regard it. The entire series of the heathen mythology has been of old, and still is, in
Germany, regarded as a mere mystical delineation of the phenomena of nature.
The elements are said to have suggested the nature of the gods and their origin; the
specific phenomena of nature may have suggested the various forms under which
the divine race appears and acts. It was a very common practice among the
astronomers of the days of Galileo, and even to a later period, to conceal their
discoveries in enigmas. May we not, with some little appearance of reason, regard
the fables of our ancestors, the knights, the dragons, the giants, the magicians and
their followers, as in some respect an esoteric teaching of the philosophy of
physics, a mystical setting forth of natural phenomena?”
“The love of our Anglo-Saxon ancestors for philosophical enigmas, as they may
be called, was undoubtedly very great,” rejoined Lathom. “I remember one given
by Mr. Wright, in his introduction to Anglo-Saxon literature. It was in these words:
 “‘I saw tread over the turf
Ten in all,
Six brothers
And their sister with them,
They had a living soul:
They hanged their skins,
Openly and manifestly,
On the wall of the hall:
To any one of them all
It was none the worse,
Nor his side the sorer:
Although they should thus,
Bereaved of covering,
And awakened by the might
Of the guardian of the skies,
Bite, with their mouths,
The rough leaves;
Clothing is renewed
To those, who, before coming forth,
Left their ornaments,
Lying in their track,
To depart over the earth.’”

“I shall not attempt to guess such an enigma,” said Thompson.

“Its solution is the butterfly; the various transformations through which it passes
from the grub until it rises with its beautiful wings, are intended to be described.
But come, as we are on enigmas, what say you to this: ‘We are a family of
seventeen, all sisters; six others claim to belong to our race, but we account them
illegitimate. We are born of iron, or of the feather that bears the bird heavenward;
by iron we die. Our fathers were three brothers, our mother’s nature is uncertain.
We teach him who desires to learn, and quickly and silently give words to him who
requires them of us.’”
“I see the solution,” said Herbert, “but yet cannot work it out; it is, doubtless, the
alphabet, in that day confined to seventeen true and six false letters; what puzzles
me is the iron, and the natures of the mother and the father.”
“The iron,” said Lathom, “is the style used in writing; the sharp point for
marking, and the broad end to rub out with; the uncertainty of the mother’s race
arises from the pen being either of reed, or quill, or even of iron; the three brothers
are the thumb and two fingers employed in writing.”
“The ‘uncertain mother’ is peculiarly applicable to these times,” said Thompson,
with a smile, “when you may vary your pen from goose to swan, and from swan to
crow; or choose between steel pens of every size and shape, and delicate nibs of
gold tipped with rubies.”
 “Come, we must leave our theories and enigmas, and return to our old story-
tellers,” said Herbert. “What tale is in preparation for us?”
“A little more demonology, as we have it in the story of
“CELESTINUS AND THE MILLER’S HORSE.”
Alexander had an only son, named Celestinus, who was very dear
to him; desirous of having him well instructed, he sent for a certain
sage, and proffered his son to him for a pupil, promising a bountiful
remuneration for his labor. The sage agreed, and took the boy home
with him. Celestinus was a diligent scholar, and made great and
satisfactory progress under the tuition of the philosopher.
One day, as the tutor and pupil were walking together through a
meadow, their attention was directed to a horse grievously afflicted
with the mange. He lay on the ground in the middle of the field, and
on either side of him two sheep were feeding, tied together by a rope
which chanced to hang over the horse’s back; irritated by the rubbing
of the cord, the poor horse rose, and naturally drew with him the two
sheep. The weight of the sheep made the rope press more and more
upon his poor back, and galled him dreadfully. Unable to endure the
pain, the horse ran towards his master’s home; the faster he ran, the
more the sheep knocked against his flanks, and by their weight
ground the cord into the sores on his back; with every struggle of the
horse and his living burdens, the cord sank deeper into the wound.
On went the horse maddened with pain; at last he reached the hut
of his master, the miller, and dashed in with his burdens through the
open door. No one was within, but a fire of logs burned brightly on
the hearth; plunging and striking with his hoofs, the horse scattered
the burning logs about the house; the flames caught the building,
and soon surrounded the poor animal. Unable to move from the
terror of the flames, there died the poor horse and the unlucky sheep,
amid the ruins of the miller’s hut.
“My son,” said the tutor, when from afar he saw the end of the
accident, “you have seen the beginning, the middle, and the end of
this incident; when you return to your study, make me some verses
upon it, and show me wherefore the house was burned. If you fail,
beware of the punishment.”
It was all in vain that Celestinus tried to coin a verse or two on
such a curious subject. He felt more than usually unpoetical; and as
for assigning a cause for the fire, he so puzzled himself with his own
arguments, as at last to begin to doubt whether there was any cause
at all. At length he left his room, and tried what a walk would do
towards making him able to poetize.
“My son,” said a venerable-looking man that met him on his
solitary ramble, “what makes you so sorrowful?”
“Pray do not trouble yourself,” replied the youth; “it is quite
useless to tell you of my trouble; you cannot help me.”
“Nay, but my son—how can we decide until we hear the cause?”
“Well, then, good father, I have got to make some verses on a
mangy horse and two sheep, and I do not know how.”
“And to decide wherefore the hut, the horse, and the sheep were
burnt.”
“Why, father, how do you know that?” exclaimed Celestinus.
“Though human to look at, I am not of this world,” replied the old
man; “come, make a contract with me, henceforth to serve me, and
care not for your master; and I will make you such a copy of verses as
never were yet seen. Come, choose; you know the alternative—the
philosopher flogs sharply.”
Celestinus hesitated a long time, but at last, through fear, he
agreed to the Devil’s proposal.
“Now, then, my son,” said the Devil, “write what I tell you. Are you
ready to begin?”
 A mangy horse lay in a field,
A sheep on either side;
Across his back a rope was hung,
To which the sheep were tied.

Teas’d by the rope, up rose the horse,

With him the sheep up swung,
On either flank, thus weighted well,
The rope his withers wrung.

Clogg’d by his living load, he seeks

Yon miller’s hut to gain;
The rope wears deeper, and his pace
Is quicken’d with the pain.

He minds not bolts, nor bars, nor logs

That on the hearthstone burn;
Nor fears with ready, scattering hoof,
The flaming pile to spurn.

Wide flies the fire, above, around,

The rafters catch the flame;
Poor Dobbin, and his fleecy load,
Are roasted in the same.

Had but that miller deigned at home,

His careful watch to keep,
He had not burnt his house, or horse,
Nor roasted both his sheep.

Delighted with the verses, Celestinus hastened to his master on his

return home. The philosopher read them with astonishment.
“Boy,” said he, “whence did you steal these verses?”
“I did not steal them, sir.”
“Come, come, boy—they are clearly not your own; tell me who
made them for you.”
“I dare not, master,” replied the boy.
“Dare not, why dare not? Come boy, tell me the truth, or abide a
worse punishment than would have awaited you had you not brought
me any verses.”
Terrified at his master’s threats, Celestinus revealed his interview
with the Devil in a human form, and his contract of service with him.
Deeply grieved at the occurrence, the preceptor ceased not to talk
with his pupil, until he had persuaded him, humbly and heartily, on
his knees, to confess to God his grievous sin in his compact with the
Devil. His confederacy with the Evil One thus renounced, Celestinus
became a good and holy man, and, after a well-spent life, resigned
his soul to God.
“Pray, Lathom, what moral did your old monk intend to draw from this
diabolical poetry?” asked Thompson.
“His application is very recondite; the preceptor is a prelate of the Church; the
mangy horse, a sinner covered with sins; the two sheep represent two preachers
bound by the cord of charity; the miller’s house is the world, and the fire,
detraction. I must admit that the application, in this case, is far less valuable or
intelligible than the story itself.”
“In an old book of moral advice,” said Herbert, “I found a description of three
madmen, that reminded me much of the five kinds described by St. Peter, as
related by your old writer. The first carried a fagot of wood, and because it was
already too heavy for him, he added more wood to it, in the hopes of thereby
making it lighter.”
“And he,” rejoined Lathom, “was a sinner, daily adding new sins to old, because
unable to bear the weight of his original errors.”
“The very same. The second madman drew water from a deep well with a sieve;
his labor was incessant, and his progress just as slow. Can you explain the nature
of his sin?”
“I can read the explanation,” rejoined Lathom, “for I have this moment found
out the source of your extract in my old monk’s book. This madman was the man
who does good, but does it sinfully, and therefore it is of no benefit. The third
madman was far worse: he carried a beam in his chariot; and wishing to enter his
court-yard, and finding the gate so narrow that it would not admit the beam, he
whipped his horse until it tumbled both itself and its master into a deep well. The
beam was worldly vanities, with which their possessor sought to enter into heaven,
but by which he was cast down into hell.”
“The belief in witchcraft,” began Herbert, “is very well illustrated by a late
publication of the Camden Society of London.”
“Nay, nay, Reginald, no more of witches now,” rejoined Lathom; “the subject
deserves far more time, attention, and illustration than we can now afford it, and
must be adjourned for the present. Let me conclude this evening with the tale of
 “THE EMPEROR CONRAD AND THE
COUNT’S SON.”
During the reign of the Emperor Conrad, there lived a certain
count of the name of Leopold, who had risen to high commands by
his bravery and his knowledge. Every one regarded the count with
favor, and loved him for his kindness to suitors, and his prowess
against the enemies of the emperor. Conrad alone looked on his
servant with an evil eye; for he envied his reputation, and would have
taken to himself the glories he had acquired, and ascribed to himself
those victories which Leopold had won.
The count, unable to endure the evil looks and hard words of the
emperor, and fearful that in time his present anger would be turned
into bitter hatred, suddenly left the court of Rome, and fled with his
wife into the forest of the Apennines. There he toiled all day, and
labored diligently to support himself and his spouse. There he knew
not what the fear of impending evil was; he had no one to envy him,
no one to covet his position or his property.
It was a bright sunny day, and the meridian sun glared with
unwonted fierceness, even through the thick trees of the forest, and
rendered the air close and heavy from lack of a breeze to move even
the highest leaves of the loftiest pines. The emperor pursued the
chase with ardor; urged on by the exhilarating cry of the hounds, he
thought not of the denseness of the forest, or the tangled nature of its
winding ways, until at last, tired and thirsty, he checked his horse in
a dark, close glade, and looked around for some hut where he might
obtain rest and refreshment.
Many were the paths which the emperor and his attendants
followed before they reached the cottage where Leopold lived in
solitude; the count recognized the sovereign, but Conrad knew not
his old servant, nor was he recognized by any of the hunting train;
refreshments, such as the homely store could furnish, were soon
placed before the emperor. It was now nigh to evening; already the
glades of the forest were growing dark, and the devious paths more
and more difficult to track out, even to the experienced eye of a
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