Biology

Intext

1.Human Embryology

2.Germinal Stage

3.Gastrulation

4.Development of Organs and Organs

System

5.Developnment of physical features

6. Clinical Signification

7.Bibiliography
 Human embryology

Human embryonic development or human embryogenesis is

the development and formation of the human embryo. It is
characterised by the processes of cell division and cellular
differentiation of the embryo that occurs during the early
stages of development.
In biological terms, the development of the human body
entails growth from a one-celled zygote to an adult human
being. Fertilization occurs when the sperm cell successfully
enters and fuses with an egg cell (ovum).
The genetic material of the sperm and egg then combine to
form the single cell zygote and the germinal stage of
development commences. Human embryonic development
covers the first eight weeks of development, which have 23
stages, called Carnegie stages.
At the beginning of the ninth week, the embryo is termed a
fetus (spelled "foetus" in British English). In comparison to the
embryo, the fetus has more recognizable external features
and a more complete set of developing organs.
Human embryology is the study of this development during
the first eight weeks after fertilization. The normal period of
gestation (pregnancy) is about nine months or 40 weeks.

The germinal stage refers to the time from fertilization through

the development of the early embryo until implantation is
completed in the uterus. The germinal stage takes around 10
days. During this stage, the zygote divides in a process called
cleavage. A blastocyst is then formed and implants in the
uterus. Embryogenesis continues with the next stage of
gastrulation, when the three germ layers of the embryo form
in a process called histogenesis, and the processes of
neurulation and organogenesis follow.
The entire process of embryogenesis involves coordinated
spatial and temporal changes in gene expression, cell growth,
and cellular differentiation. A nearly identical process occurs
in other species, especially among chordates.
 Germinal stage

Fertilization
Fertilization takes place when the spermatozoon has
successfully entered the ovum and the two sets of genetic
material carried by the gametes fuse together, resulting in the
zygote (a single diploid cell). This usually takes place in the
ampulla of one of the fallopian tubes. The zygote contains the
combined genetic material carried by both the male and
female gametes which consists of the 23 chromosomes from
the nucleus of the ovum and the 23 chromosomes from the
nucleus of the sperm. The 46 chromosomes undergo
changes prior to the mitotic division which leads to the
formation of the embryo having two cells.

Successful fertilization is enabled by three processes, which

also act as controls to ensure species-specificity. The first is
that of chemotaxis which directs the movement of the sperm
towards the ovum. Secondly, an adhesive compatibility
between the sperm and the egg occurs. With the sperm
adhered to the ovum, the third process of acrosomal reaction
takes place; the front part of the spermatozoan head is
capped by an acrosome which contains digestive enzymes to
break down the zona pellucida and allow its entry.

The entry of the sperm causes calcium to be released which

blocks entry to other sperm cells. A parallel reaction takes
place in the ovum called the zona reaction. This sees the
release of cortical granules that release enzymes which
digest sperm receptor proteins, thus preventing polyspermy.
 The granules also fuse with the plasma membrane and
modify the zona pellucida in such a way as to prevent further
sperm entry.

SIGNIFICANCE OF FERTILIZATION:
Stimulates the secondary oocyte to complete its maturation to
form haploid ovum.
Restores the diploid number of chromosomes in the zygote.
Activates the egg to develop into a new individual by
repeated mitotic divisions.
Egg becomes metabolically more active.
Combines characters of two parents. This causes variations
and helps in evolution.
Cleavage
The beginning of the cleavage process is marked when the
zygote divides through mitosis into two cells. This mitosis
continues and the first two cells divide into four cells, then into
eight cells and so on. Each division takes from 12 to 24
hours. The zygote is large compared to any other cell and
undergoes cleavage without any overall increase in size. This
means that with each successive subdivision, the ratio of
nuclear to cytoplasmic material
increases.

Initially, the dividing cells, called

blastomeres (blastos Greek for
sprout), are undifferentiated and
aggregated into a sphere
enclosed within the zona
pellucida of the ovum. When eight blastomeres have formed,
they start to compact. They begin to develop gap junctions,
enabling them to develop in an integrated way and co-
ordinate their response to physiological signals and
environmental cues. When the cells number around sixteen,
the solid sphere of cells within the zona pellucida is referred
to as a morula.

Blastulation
Blastocyst with an inner cell mass and trophoblast
Cleavage itself is the first stage in Blastulation, the process of
forming the blastocyst. Cells differentiate into an outer layer of
cells called the trophoblast, and an inner cell mass. With
further compaction the individual outer blastomeres, the
trophoblasts, become indistinguishable. They are still
enclosed within the zona pellucida. This compaction serves to
make the structure watertight, containing the fluid that the
cells will later secrete. The inner mass of cells differentiate to
become embryoblasts and polarise at one end. They close
together and form gap junctions, which facilitate cellular
communication. This polarisation leaves a cavity, the
blastocoel, creating a structure that is now termed the
blastocyst. (In animals other than mammals, this is called the
blastula).

The trophoblasts secrete fluid

into the blastocoel. The
resulting increase in size of
the blastocyst causes it to
hatch through the zona
pellucida, which then
disintegrates. This process is
called zona hatching and it takes place on the sixth day of
embryo development, immediately before the implantation
process. The hatching of the human embryo is supported by
proteases secreted by the cells of the blastocyst, which digest
proteins of the zona pellucida, giving rise to a hole. Then, due
to the rhythmic expansion and contractions of the blastocyst,
an increase of the pressure inside the blastocyst itself occurs,
the hole expands and finally the blastocyst can emerge from
this rigid envelope.

The inner cell mass will give rise to the pre-embryo, the
amnion, yolk sac and allantois, while the fetal part of the
placenta will form from the outer trophoblast layer. The
embryo plus its membranes is called the conceptus, and by
this stage the conceptus has reached the uterus. The zona
pellucida ultimately disappears completely, and the now
exposed cells of the trophoblast allow the blastocyst to attach
itself to the endometrium, where it will implant.
The formation of the hypoblast and epiblast, which are the
two main layers of the bilaminar germ disc, occurs at the
beginning of the second week. Both the embryoblast and the
trophoblast will turn into two sub-layers. The inner cells will
turn into the hypoblast layer, which will surround the other
layer, called the epiblast, and these layers will form the
embryonic disc that will develop into the embryo.

The trophoblast will also

develop two sub-layers: the
cytotrophoblast, which is in
front of the
syncytiotrophoblast, which in
turn lies within the
endometrium. Next, another layer called the exocoelomic
membrane or Heuser's membrane will appear and surround
the cytotrophoblast, as well as the primitive yolk sac. The
syncytiotrophoblast will grow and will enter a phase called
lacunar stage, in which some vacuoles will appear and be
filled by blood in the following day. The development of the
yolk sac starts with the hypoblastic flat cells that form the
exocoelomic membrane, which will coat the inner part of the
cytotrophoblast to form the primitive yolk sac. An erosion of
the endothelial lining of the maternal capillaries by the
syncytiotrophoblastic cells results in the formation of the
maternal sinusoids from where the blood will begin to
penetrate and flow into and through the trophoblastic lacunae
to give rise to the uteroplacental circulation. Subsequently,
new cells derived from yolk sac will be established between
trophoblast and exocoelomic membrane and will give rise to
extra-embryonic mesoderm, which will form the chorionic
cavity.

At the end of the second week of development, some cells of

the trophoblast penetrate and form rounded columns into the
syncytiotrophoblast. These columns are known as primary
villi. At the same time, other migrating cells form into the
exocoelomic cavity a new cavity named the secondary or
definitive yolk sac, smaller than the primitive yolk sac.
Implantation
After ovulation, the endometrial lining becomes transformed
into a secretory lining in preparation of accepting the embryo.
It becomes thickened, with its secretory glands becoming
elongated, and is increasingly vascular. This lining of the
uterine cavity (or womb) is now known as the decidua, and it
produces a great number of large decidual cells in its
increased inter glandular tissue.
The blastomeres in the blastocyst are arranged into an outer
layer called the trophoblast. The trophoblast then
differentiates into an inner layer, the cytotrophoblast, and an
outer layer, the syncytiotrophoblast. The cytotrophoblast
contains cuboidal epithelial cells and is the source of dividing
cells, and the syncytiotrophoblast is a syncytial layer without
cell boundaries.

The syncytiotrophoblast implants the blastocyst in the

decidual epithelium by projections of chorionic villi, forming
the embryonic part of the placenta. The placenta develops
once the blastocyst is implanted, connecting the embryo to
the uterine wall. The decidua here is termed the decidua
basalis; it lies between the blastocyst and the myometrium
and forms the maternal part of the placenta.
The implantation is assisted by hydrolytic enzymes that
erode the epithelium. The syncytiotrophoblast also produces
human chorionic gonadotropin, a hormone that stimulates the
release of progesterone from the corpus luteum.
Progesterone enriches the uterus with a thick lining of blood
vessels and capillaries so that it can oxygenate and sustain
the developing embryo. The uterus liberates sugar from
stored glycogen from its cells to nourish the embryo. The villi
begin to branch and contain blood vessels of the embryo.
Other villi, called terminal or free villi, exchange nutrients.
The embryo is joined to the trophoblastic shell by a narrow
connecting stalk that develops into the umbilical cord to
attach the placenta to the embryo. Arteries in the decidua are
remodelled to increase the maternal blood flow into the
intervillous spaces of the placenta, allowing gas exchange
and the transfer of nutrients to the embryo. Waste products
from the embryo will diffuse across the placenta.

As the syncytiotrophoblast starts to penetrate the uterine wall,

the inner cell mass (embryoblast) also develops. The inner
cell mass is the source of embryonic stem cells, which are
pluripotent and can develop into any one of the three germ
layer cells, and which have the potency to give rise to all the
tissues and organs.
Gastrulation
The primitive streak, a linear collection of cells formed by the
migrating epiblast, appears, and this marks the beginning of
gastrulation, which takes place around the seventeenth day
(week 3) after fertilization. The process of gastrulation
reorganises the two-layer embryo into a three-layer embryo,
and also gives the embryo its specific head-to-tail, and front-
to-back orientation, by way of the primitive streak which
establishes bilateral symmetry.

A primitive node (or primitive knot) forms in front of the

primitive streak which is the organiser of neurulation. A
primitive pit forms as a depression in the centre of the
primitive node which connects to the notochord which lies
directly underneath. The node has arisen from epiblasts of
the amniotic cavity floor, and it is this node that induces the
formation of the neural plate which serves as the basis for the
nervous system.
The neural plate will form opposite the primitive streak from
ectodermal tissue which thickens and flattens into the neural
plate. The epiblast in that region moves down into the streak
at the location of the primitive pit where the process called
ingression, which leads to the
formation of the mesoderm takes
place. This ingression sees the
cells from the epiblast move into
the primitive streak in an epithelial-
mesenchymal transition; epithelial
cells become mesenchymal stem
cells, multipotent stromal cells that
can differentiate into various cell types. The hypoblast is
pushed out of the way and goes on to form the amnion. The
epiblast keeps moving and forms a second layer, the
mesoderm. The epiblast has now differentiated into the three
germ layers of the embryo, so that the bilaminar disc is now a
trilaminar disc, the gastrula.

The three germ layers are the ectoderm, mesoderm and

endoderm, and are formed as three overlapping flat discs. It
is from these three layers that all the structures and organs of
the body will be derived through the processes of
somitogenesis, histogenesis and organogenesis.
The embryonic endoderm is formed by invagination of
epiblastic cells that migrate to the hypoblast, while the
mesoderm is formed by the cells that develop between the
epiblast and endoderm. In general, all germ layers will derive
from the epiblast. The upper layer of ectoderm will give rise to
the outermost layer of skin, central and peripheral nervous
systems, eyes, inner ear, and many connective tissues.The
middle layer of mesoderm will give rise to the heart and the
beginning of the circulatory system as well as the bones,
muscles and kidneys. The inner layer of endoderm will serve
as the starting point for the development of the lungs,
intestine, thyroid, pancreas and bladder.

Following ingression, a blastopore develops where the cells

have ingressed, in one side of the embryo and it deepens to
become the archenteron, the first formative stage of the gut.
As in all deuterostomes, the blastopore becomes the anus
whilst the gut tunnels through the embryo to the other side
where the opening becomes the mouth. With a functioning
digestive tube, gastrulation is now completed and the next
stage of neurulation can begin.
Neurulation
Following gastrulation, the ectoderm gives rise to epithelial
and neural tissue, and the gastrula is now referred to as the
neurula. The neural plate that has formed as a thickened
plate from the ectoderm, continues to broaden and its ends
start to fold upwards as neural folds. Neurulation refers to this
folding process whereby the neural plate is transformed into
the neural tube, and this takes place during the fourth week.
They fold, along a shallow neural groove which has formed
as a dividing median line in the neural plate.
This deepens as the folds continue to gain height, when they
will meet and close together at the neural crest. The cells that
migrate through the most cranial part of the primitive line form
the paraxial mesoderm, which will give rise to the
somitomeres that in the process of somitogenesis will
differentiate into somites that will form the sclerotomes, the
syndetomes,
the myotomes and the dermatomes to form cartilage and
bone, tendons, dermis (skin), and muscle. The intermediate
mesoderm gives rise to the urogenital tract and consists of
cells that migrate from the middle region of the primitive line.
Other cells migrate through the caudal part of the primitive
line and form the lateral mesoderm, and those cells migrating
by the most caudal part contribute to the extraembryonic
mesoderm.

The embryonic disc begins flat and round, but eventually

elongates to have a wider cephalic part and narrow-shaped
caudal end. At the beginning, the primitive line extends in
cephalic direction and 18 days after fertilization returns
caudally until it disappears. In the cephalic portion, the germ
layer shows specific differentiation at the beginning of the
fourth week, while in the caudal portion it occurs at the end of
the fourth week. Cranial and caudal neuropores become
progressively smaller until they close completely (by day 26)
forming the neural tube.
 Development of organs and organ systems
Organogenesis is the development of the organs that begins
during the third to eighth week, and continues until birth.
Sometimes full development, as in the lungs, continues after
birth. Different organs take part in the development of the
many organ systems of the body.

Blood

Haematopoietic stem cells that give rise to all the blood cells
develop from the mesoderm. The development of blood
formation takes place in clusters of blood cells, known as
blood islands, in the yolk sac. Blood islands develop outside
the embryo, on the umbilical vesicle, allantois, connecting
stalk, and chorion, from mesodermal hemangioblasts.

In the centre of a blood island, hemangioblasts form the

haematopoietic stem cells that are the precursor to all types
of blood cell. In the periphery of a blood island the
hemangioblasts differentiate into angioblasts, the precursors
to the blood vessels.[20]

Heart and circulatory system (heart development)

The heart is the first functional organ to develop and starts to

beat and pump blood at around 22 days. Cardiac myoblasts
and blood islands in the splanchnopleuric mesenchyme on
each side of the neural plate give rise to the cardiogenic
region. This is a horseshoe-shaped area near to the head of
the embryo. By day 19, following cell signalling, two strands
begin to form as tubes in this region, as a lumen develops
within them. These two endocardial tubes grow and by day 21
have migrated towards each other and fused to form a single
primitive heart tube, the tubular heart. This is enabled by the
folding of the embryo which pushes the tubes into the
thoracic cavity.

Also at the same time that the endocardial tubes are forming,
vasculogenesis (the development of the circulatory system)
has begun. This starts on day 18 with cells in the
splanchnopleuric mesoderm differentiating into angioblasts
that develop into flattened endothelial cells. These join to form
small vesicles called angiocysts which join up to form long
vessels called angioblastic cords.
These cords develop into a pervasive network of plexuses in
the formation of the vascular network. This network grows by
the additional budding and sprouting of new vessels in the
process of angiogenesis. Following vasculogenesis and the
development of an early vasculature, a stage of vascular
remodelling takes place.

The tubular heart quickly forms five distinct regions. From

head to tail, these are the infundibulum, bulbus cordis,
primitive ventricle, primitive atrium, and the sinus venosus.
Initially, all venous blood flows into the sinus venosus, and is
propelled from tail to head to the truncus arteriosus.
This will divide to form the aorta and pulmonary artery; the
bulbus cordis will develop into the right (primitive) ventricle;
the primitive ventricle will form the left ventricle; the primitive
atrium will become the front parts of the left and right atria
and their appendages, and the sinus venosus will develop
into the posterior part of the right atrium, the sinoatrial node
and the coronary sinus.

Cardiac looping begins to shape the heart as one of the

processes of morphogenesis, and this completes by the end
of the fourth week. Programmed cell death (apoptosis) at the
joining surfaces enables fusion to take place. In the middle of
the fourth week, the sinus venosus receives blood from the
three major veins: the vitelline, the umbilical and the common
cardinal veins.

During the first two months of development, the interatrial

septum begins to form. This septum divides the primitive
atrium into a right and a left atrium. Firstly it starts as a
crescent-shaped piece of tissue which grows downwards as
the septum primum. The crescent shape prevents the
complete closure of the atria allowing blood to be shunted
from the right to the left atrium through the opening known as
the ostium primum. This closes with further development of
the system but before it does, a second opening (the ostium
secundum) begins to form in the upper atrium enabling the
continued shunting of blood.

A second septum (the septum secundum) begins to form to

the right of the septum primum. This also leaves a small
opening, the foramen ovale which is continuous with the
previous opening of the ostium secundum. The septum
primum is reduced to a small flap that acts as the valve of the
foramen ovale and this remains until its closure at birth.
Between the ventricles the septum inferius also forms which
develops into the muscular interventricular septum.
Digestive system(Development of the digestive system)
The digestive system starts to develop from the third week
and by the twelfth week, the organs have correctly positioned
themselves.

Respiratory system (Lung § Development)

The respiratory system develops from the lung bud, which
appears in the ventral wall of the foregut about four weeks
into development. The lung bud forms the trachea and two
lateral growths known as the bronchial buds, which enlarge at
the beginning of the fifth week to form the left and right main
bronchi. These bronchi in turn form secondary (lobar) bronchi;
three on the right and two on the left (reflecting the number of
lung lobes). Tertiary bronchi form from secondary bronchi.

While the internal lining of the larynx originates from the lung
bud, its cartilages and muscles originate from the fourth and
sixth pharyngeal arches.

Urinary system(Development of the urinary system and

Kidney development)

Kidneys
Three different kidney systems form in the developing
embryo: the pronephros, the mesonephros and the
metanephros. Only the metanephros develops into the
permanent kidney. All three are derived from the intermediate
mesoderm.
Pronephros
The pronephros derives from the intermediate mesoderm in
the cervical region. It is not functional and degenerates before
the end of the fourth week.

Mesonephros
The mesonephros derives from intermediate mesoderm in the
upper thoracic to upper lumbar segments. Excretory tubules
are formed and enter the mesonephric duct, which ends in
the cloaca. The mesonephric duct atrophies in females, but
participate in development of the reproductive system in
males.

Metanephros
The metanephros appears in the fifth week of development.
An outgrowth of the mesonephric duct, the ureteric bud,
penetrates metanephric tissue to form the primitive renal
pelvis, renal calyces and renal pyramids. The ureter is also
formed.

Bladder and urethra

Between the fourth and seventh weeks of development, the
urorectal septum divides the cloaca into the urogenital sinus
and the anal canal. The upper part of the urogenital sinus
forms the bladder, while the lower part forms the urethra.
Reproductive system (Development of the reproductive
system)
Integumentary system (Human skin color)
The superficial layer of the skin, the epidermis, is derived
from the ectoderm. The deeper layer, the dermis, is derived
from mesenchyme.

The formation of the epidermis begins in the second month of

development and it acquires its definitive arrangement at the
end of the fourth month. The ectoderm divides to form a flat
layer of cells on the surface known as the periderm. Further
division forms the individual layers of the epidermis.

The mesenchyme that will form the dermis is derived from

three sources:

1.The mesenchyme that forms the dermis in the limbs and

body wall derives from the lateral plate mesoderm
2.The mesenchyme that forms the dermis in the back derives
from paraxial mesoderm
3.The mesenchyme that forms the dermis in the face and
neck derives from neural crest cells
 Nervous system
Development of the nervous system in humans and
Development of the human brain

Late in the fourth week, the superior part of the neural tube
bends ventrally as the cephalic flexure at the level of the
future midbrain—the mesencephalon.Above the
mesencephalon is the prosencephalon (future forebrain) and
beneath it is the rhombencephalon (future hindbrain).

Cranial neural crest cells migrate to the pharyngeal arches as

neural stem cells, where they develop in the process of
neurogenesis into neurons.

The optical vesicle (which eventually becomes the optic

nerve, retina and iris) forms at the basal plate of the
prosencephalon. The alar plate of the prosencephalon
expands to form the cerebral hemispheres (the
telencephalon) whilst its basal plate becomes the
diencephalon. Finally, the optic vesicle grows to form an optic
outgrowth.
Development of physical features

From the third to the eighth week the face and neck develop.

Ears (Ear & Development)

The inner ear, middle ear and outer ear have distinct
embryological origins.

Inner ear
At about 22 days into development, the ectoderm on each
side of the rhombencephalon thickens to form otic placodes.
These placodes invaginate to form otic pits, and then otic
vesicles. The otic vesicles then form ventral and dorsal
components.

The ventral component forms the saccule and the cochlear

duct. In the sixth week of development the cochlear duct
emerges and penetrates the surrounding mesenchyme,
travelling in a spiral shape until it forms 2.5 turns by the end
of the eighth week. The saccule is the remaining part of the
ventral component. It remains connected to the cochlear duct
via the narrow ductus reuniens.

The dorsal component forms the utricle and semicircular

canals.
Middle ear

The first pharyngeal pouch lengthens and expands to form

the tubotympanic recess. This recess differentiates to form
most of the tympanic cavity of the middle ear, and all of the
Eustachian or auditory tube. The narrow auditory tube
connects the tympanic cavity to the pharynx

The bones of the middle ear, the ossicles, derive from the
cartilages of the pharyngeal arches. The malleus and incus
derive from the cartilage of the first pharyngeal arch, whereas
the stapes derives from the cartilage of the second
pharyngeal arch.

Outer ear
The external auditory meatus develops from the dorsal
portion of the first pharyngeal cleft. Six auricular hillocks,
which are mesenchymal proliferations at the dorsal aspects of
the first and second pharyngeal arches, form the auricle of
the ear.

Eyes (Eye development)

The eyes begin to develop from the third week to the tenth
week.
 Limbs (Limb development and Limb bud)
Zone of polarizing activity and polymelia
At the end of the fourth week limb development begins. Limb
buds appear on the ventrolateral aspect of the body. They
consist of an outer layer of ectoderm and an inner part
consisting of mesenchyme which is derived from the parietal
layer of lateral plate mesoderm.
Ectodermal cells at the distal end of the buds form the apical
ectodermal ridge, which creates an area of rapidly
proliferating mesenchymal cells known as the progress zone.
Cartilage (some of which ultimately becomes bone) and
muscle develop from the mesenchyme

Clinical significance

Toxic exposures in the embryonic period can be the cause of

major congenital malformations, since the precursors of the
major organ systems are now developing.

Each cell of the preimplantation embryo has the potential to

form all of the different cell types in the developing embryo.
This cell potency means that some cells can be removed
from the preimplantation embryo and the remaining cells will
compensate for their absence. This has allowed the
development of a technique known as preimplantation
genetic diagnosis, whereby a small number of cells from the
preimplantation embryo created by IVF, can be removed by
biopsy and subjected to genetic diagnosis. This allows
embryos that are not affected by defined genetic diseases to
be selected and then transferred to the mother's uterus.

Sacrococcygeal teratomas, tumours formed from different

types of tissue, that can form, are thought to be related to
primitive streak remnants, which ordinarily disappear
First arch syndromes are congenital disorders of facial
deformities, caused by the failure of neural crest cells to
migrate to the first pharyngeal arch.
 Bibiliography

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