Teratogens and Teratogenesis

Academic Script

Dear Students! A very warm welcome to all of you in this programme of developmental biology!
Today, we are going to learn about an important aspect of implications of developmental biology in
terms of ‘teratogenesis’.

Introduction

Let us start with the introduction of ‘teratology’ first.

Teratology is the study of formation of ‘congenital anomalies in developing embryo or foetus’ which
may lead to birth defects or even death. Teratogenesiscan be defined as ‘formation of congenital
defects due to exposure to teratogens’. The word ‘teratogen’ originates from the Greek word used
for monster or marvel to describe malformed infants, called ‘teratos’. The term ‘teratogen’ is cited in
the context of the agent responsible for producing certain anatomical defects in an embryo that was
previously differentiating normally. More precisely, teratogens are biological, chemical or physical
substances that may produce physical or functional defects in the developing embryo or foetus after
the exposure of pregnant woman to them.

Nowadays, birth defects are the leading cause of infant mortality in the world, which accounts for
approximately 20% of the total infant mortality observed. Of these defects, about 20-25% are of
genetic origin and 65-75% are of unknown etiology i.e. multifactorial, polygenic, spontaneous errors
of development and synergistic interactions of teratogens. Out of this 65-75%, approximately more
than 5% of birth defects are the result of exposure to various teratogens.

Adverse effects of teratogens are normally associated with physical malformations. About 2% of
human infants are born with a readily observable anatomical abnormality. Apart from these,
problems in the behavioral or emotional development of the child as well as decreased intellectual
quotient (IQ) in the child are also encountered. Additionally, teratogens may also affect pregnancies
and cause complications such as pre-term labors, spontaneous abortions or miscarriages.

In terms of mechanism of cellular action, a teratogen may potentially affect embryogenesis by

causing gene mutation; chromosomal breakage; non-disjunction; depletion or inhibition of
precursors or substrates; depletion of energy sources; inhibition of enzymes or changes in
membrane integrity. These effects may lead to cell death, reduced cell division, reduced interaction
between cells, disruption of cell migration or mechanical disruption with the ultimate result of failure
in the particular organ system development.
Principles of Teratology

Now, let’s know about certain essential principles of teratology one by one.

 The first principle states that teratogens act with specificity and produce specific abnormalities at
specific developmental stage during gestation. For example, thalidomide produces limb
phocomelia, while valproic acid and carbamazepine produce neural tube defects.
 The second principle implies that the effect of a teratogen on the developing organism depends
on critical period during pregnancy in which the embryo or foetus is exposed to the teratogen.
Some teratogens cause damage only during specific days or weeks in early pregnancy. Other
teratogens are harmful at any time during the pregnancy. For example, for behavioral
teratogens, there is no safe period because the brain and nervous system can be harmed
throughout the pregnancy.
 According to the third principle, teratogenic specificity is also applied to species. For example,
aspirin and corticosteroids have been found to be teratogenic in mice and rats but appear to be
safe in humans. On the other hand, thalidomide produces phocomelia in primates but not in
rodents. Within a given species also, a given teratogen may affect many organ systems. For
example, administering thalidomide between days 35 and 37 causes ear malformations while
administration of the agent between days 41 and 44 causes phocomelia.
 As per the fourth principle, teratogens are found to be associated with recognizable patterns of
malformations. For example, phenytoin with foetal hydantoin syndrome and coumarin
anticoagulants with foetal warfarin syndrome.
 The fifth principle implies that teratogens generally demonstrate a dose-effect relationship
ranging from no observable effects to total lethality. At any given time, an embryo can respond to
a teratogen in one of three ways: (1) At low dosage, there can be no effect; (2) at intermediate
dose the characteristic pattern of malformations will result and (3) at high dosage the embryo will
be killed.
 According to sixth principle, teratogens must reach the developing conceptus in sufficient
amounts to cause their effects. Large molecules with higher molecular weights do not easily
cross the placenta into the embryonic-foetal bloodstream to exert potential teratogenic effect.
Other factors influencing the rate and extent of placental transfer of xenobiotics include polarity,
lipid solubility and the existence of a specific protein carrier.
 The seventh principle explains that teratogens act via a specific mechanism on developing cells
and tissues to initiate a cascade of altered developmental events.
 The next principle states that teratogenic effects are dependent on the nature of the teratogen;
including chemical properties of the substance, route of exposure, maternal or foetal bio-
activation, placental transport, etc.
 As per the modern refined principles of the teratology, teratogens produce a consistent deviation
from normal development. Deviation may include: (1) death, (2) malformation, (3)
growth retardation, or (4) functional defect.
 The last principle states that the genotype i.e. genetic make-up of the mother and the foetus
determines the efficacy of a teratogen. Presence or absence of certain genes may make the
developing organism more susceptible to the effect of a teratogen.

Variability in teratogenic response is also found to be associated with other environmental or

morphologic factors such as maternal or foetal weight, in utero position of the foetus, uterine
vasculature, diet as well as drug interactions.

Causes of Teratogenesis

Let’s see how and why the things go wrong during embryological development.

A particular birth defect may be the outcome of action of many different factors as well as various
mechanisms. The major causes of teratogenesis can broadly be classified as:
 Exposure to toxic substances, such as, drugs and environmental toxins during pregnancy in
humans
 Vertically transmitted infections
 Lack of nutrients such as deficiency of folic acid in the nutrition during pregnancy for humans
can result in defect called ‘spina bifida’
 Physical restraint like potter syndrome due to oligohydramnios in the human and
 Genetic disorders
 In addition, maternal determinants, including drug administration, distribution, metabolism and
excretion, may also play an important role in teratogenesis.

Classification of Teratogens:

Dear students, let us move on to the essential part of this lecture by obtaining detailed information
about classification of teratogens.

Teratogens are classified into four types: physical agents, infectious agents, maternal metabolic
conditions and finally, chemicals as well as drugs.
Let’s get an overview of the first type of teratogens as ‘Physical Agents’ in terms of Ionizing
Radiation.

High dose of ionizing radiation over a short period of time leads to abnormal brain development,
mental retardation and leukemia in children. The common anomalies include small head
circumference called microcephaly and small eyes known as microphthalmia. Even a single
computer tomography scan employed as a tool of diagnosis creates a radiation exposure dose that
equals to tens of X-rays and should be avoided during pregnancy.

The second type of teratogens includes various ‘Infectious Agents’ such as protozoa, bacteria and
viruses.

Let’s begin with Toxoplasma.

Toxoplasma is a single-celled parasitic protozoan. The toxoplasma infection is often obtained by

eating contaminated meat, drinking contaminated water, or coming into contact with infected cat
faeces. Toxoplasma infection during pregnancy can be extremely dangerous to the baby. It can lead
to spontaneous abortion or delivery of the dead infant; or the baby might have underdevelopment of
the brain, brain calcifications, blindness and seizures.

Now, let us see adverse effects of infection caused by Syphilis Bacteria.

Syphilis is a sexually transmitted bacterial disease caused by Treponemapallidum. If a pregnant

woman has syphilis and is not treated quickly, than these tiny bacteria travel with her blood to the
baby’s body. Syphilis infection can be a cause of foetal death and spontaneous abortion, or can
result in the delivery of the dead baby, or the baby can die within several days of life. If the baby
survives, there is a high risk that this baby will have copious nasal discharge packed with
treponemes and severe inflammatory reaction as a consequence, destroying nasal cartilages and
bones. The baby will likely suffer from liver and spleen enlargement and dysfunction, meningitis and
inflammatory skin rash as a part of symptoms of early congenital syphilis. Some babies will
demonstrate symptoms of late congenital syphilis around the eight years of age: their vision will
become deteriorated due to inflammatory changes in eyes, some of their central permanent teeth
will have unusual conic shape and notching, and they may become deaf with complaining of vertigo
and ringing in the ears. Their bones will be deformed, resulting in the look of “saddle” nose and
“saber” shins.

The third type of infectious agent is Viruses.

Viruses are incredibly small live particles composed of RNA or DNA requiring the host cells for
replication. Certain types of viruses are well-known to create birth defects. Rubella or German
measles virus exposure to the foetus can be a culprit of congenital heart defects, deafness and
blindness. Rubella virus can also be a cause of abnormal brain development and other internal
organs and creates characteristic bluish-red skin lesions known as “blueberry muffin spots.”

Cytomegalovirus (CMV) infection is the most ubiquitous type of foetal infection. CMV can be a
cause of mental retardation, cerebral calcifications, intrauterine growth retardation, blindness,
deafness, dysfunction of the liver and spleen, jaundice or lesions on the skin known as “blueberry
muffin spots.” Infection of the early embryo during the first trimester most commonly results in the
spontaneous termination.

Herpes virus infection, in about 5% of cases, can infect a baby in the uterus. The consequences are
catastrophic—from foetal death to permanent problems like underdevelopment and/or calcification
of the brain, blindness, or abnormal limb formation. If the herpes virus was acquired by the baby
during or just after the delivery, the baby will get herpetic pneumonia or meningoencephalitis.

Varicella zoster virus is a cause of chickenpox mostly in children and herpes zoster mostly in
seniors. If a pregnant woman would possess varicella zoster virus for the first time during the
pregnancy, there is 25-40% risk that the foetus will have underdeveloped limbs, brain or eye
malformations and specific zig-zag skin scarring. An infant can also suffer from severe varicella
zoster pneumonia.

Now, let’s learn in detail about the third type of teratogens as ‘Maternal Metabolic Conditions’.

The first maternal metabolic condition is Diabetes mellitus. Hyperglycemia can be considered as
the key in pathogenesis of diabetic embryopathy. The gastrulation and neurulation stages of
development are particularly sensitive to hypoglycemia and result in growth retardation as well as
cranial and caudal neural tube defects (NTDs).

The second metabolic condition is Obesity. During pregnancy, obesity is associated with adverse
outcomes that include hypertension, gestational diabetes mellitus, increased risk of birth defects
and foetal death.

The third maternal condition is presence of Thyroid disorders. They include disorders in which the
thyroid gland malfunctions, thereby producing abnormal amounts of the thyroid hormones, thyroxine
and triiodothyronine, which regulate the metabolism. Thyroid disorders can cause a number of
teratogenic effects to a developing foetus, as well as adverse effects on pregnancy such as
miscarriage, premature separation of the placenta from the uterine wall (placental abruption),
preterm labor and lower IQ scores in the children. It leads to hypothyroidism or hyperthyroidism in
foetus. Hypothyroidism occurs when the foetal thyroid glands have been suppressed by antithyroid
drugs like propylthiouracil, carbimazole, radioactive iodine or possibly maternal antibodies.
Hyperthyroidism occurs inthe presence of thyroid stimulating globulins which may result in
thyrotoxicity in the foetus and newborn. Affected infants have goiter, exophthalmos, restlessness,
tachycardia, ravenous appetite, hyperthermia, cardiomegaly, cardiac failure and
hepatosplenomegaly.

Hyperparathyroidism is the fourth metabolic condition.Infants of mothers with parathyroid

dysfunction may have transient hyperparathyroidism during the foetal and neonatal periods. It
occurs in response to low maternal and foetal serum calcium concentration mediated by maternal
parathyroid dysfunction which results in intrauterine growth retardation, pulmonary artery stenosis
and muscle hypotonia.

Cretinism and iodine deficiency account for next maternal condition.Iodine deficiency is the cause
of endemic goiter and cretinism due to deficiency or insufficient availability of thyroxine at the feto-
placental level. In early pregnancy, iodine deficiency induces a critical decrease of T4 levels with
consequent TSH increase leading to hypothyroidism in about 50% of iodine-deficient pregnant
women.

Myotonic dystrophy also acts as one of the maternal metabolic conditions. Infants born of women
with myotonic dystrophy may show foetal hypokinesia and generalized weakness and may
experience difficulty in respiration as well as feeding. The face characteristically shows tenting of
the upper lip, ptosis and absence of movement and anterior cupping of the pinnas with presence of
clubfoot and slow postnatal growth.
The next metabolic condition includes Phenylketonuria.Maternal phenylketonuria (PKU) induced
defects are directly related to the maternal phenylalalnine level. When the level exceeds 20 mg/ml,
infants suffer from mental retardation, microcephaly, intrauterine and postnatal growth retardation,
cardiac malformations, dislocated hips and other anomalies. One-fourth of the pregnancies abort
spontaneously due to this reason.

The last type of maternal metabolic condition is referred to asThermodisruptions.It can be

categorized by hyperthermia or hypothermia. Hyperthermia is defined as a body temperature of at
least 38.9°C and is an anti-mitotic teratogen after exposure between weeks 4 and 14. Hyperthermia
causes central nervous system malformations, abdominal wall defects, defects of the eye and
palate, limb reduction, neural tube defects, mental deficiency, seizures spontaneous abortions and
various cardiovascular abnormalities. Hypothermia is defined as a core body temperature of less
than 35°C. Infant with multiple congenital defects, severe disruptive defects of the brain and distal
spinal cord may be observed due to hypothermia.

The forth type of teratogens in the classification comprise of ‘Chemicals and Drugs’.

Let us first understand the Chemicals as teratogens with appropriate examples.

1. Mercury: Organic mercury like methylmercury compounds can be extremely dangerous for the
developing foetus in a small dose. Organic mercury exposure can lead to atrophy of the granular
layer of the cerebellum and damage to neural system, mental retardation, behavioral and
cognitive problems as well as blindness in a baby.

2. Lead: A woman with lead poisoning can pass lead on to her foetus if she becomes pregnant.
This happens because more than 90% of the lead may be stored in bone and released into the
bloodstream years later. Lead crosses the placenta as early as the 12 th to 14th weeks of
gestation and accumulates in foetal tissue. The adverse effects of lead include spontaneous
abortion, abnormal and delayed mental or physical development of the child and stillbirth. The
VACTERL (i.e. vertebral, anal, cardiac, tracheoesophageal fistula, renal and limb abnormalities)
association has been reported with prenatal exposure to high lead levels.

3. Potassium iodine: Large doses of potassium iodine, found in anti-cough syrups or medical
cocktails for x-ray diagnostic, can be a cause of abnormal thyroid development and function in a
foetus. This effect will lead to mental retardation or cretinism in a child.

4. Polychlorinated biphenyls (PCBs): PCBs were linked to delayed foetal growth, abnormal
neural system development and impaired behavioral and cognitive functions in a child.

5. Alcohol:Alcohol can cross the placenta and affect the foetus. Excessive maternal drinking while
pregnancy can cause foetal alcohol spectrum disorders (FASD). Physically, children with FASD
may have a small head size; abnormal facial featuressuch as small eyes and nose, thin upper
lip;ear abnormalities;small nails;cleft palate and cardiac anomalies. Cognitively, these children
may have poor judgment, learning difficulties, behavioral problems and mental retardation.
6. Cigarette Smoking: Cigarette smoking women have higher risk of miscarriage, stillbirth, low
birth weight, premature birth, Sudden Infant Death Syndrome (SIDS), possibly increase in
developmental delays and infant with cleft palate.

7. Cocaine:Cocaine use during pregnancy has been associated with detachment of the placenta,
prematurity, foetal loss, decreased birth weight, microcephaly, limb abnormalities, urinary tract
malformations and poorer neurodevelopmental performance.

Now, let’s quickly get an overview of ‘Proven Teratogenic Drugs in Humans’.

1. Thalidomide:More than any other event, the thalidomide tragedy alerted the world maximum to
the teratogenic potential of the drugs. A new era of teratology was initiated as a result of clinical
use of thalidomide by pregnant women for the relief of morning sickness. Thalidomide was
marketed in the year 1956 and was available for four years before its teratogenicity was
recognized. Thalidomide produced malformations limited to tissues of mesodermal origin;
primarily limbs, ears, cardiovascular system and gut musculature. Malformations resulted from
the repeated use as well as from single ingestions during the critical period from 27 th day to 40th
day of gestation. Numbers of cases of phocomelia were reported due to thalidomide
teratogenecity, which is characterized by rare type of congenital malformation, with the
shortening or total absence of limbs. Typically, the upper limbs were more severely involved than
the lower limbs. Polydactyly, syndactyly, oligodactyly were also reported in certain cases.

2. Angiotensin converting enzyme inhibitors (ACEI) (Captopril, Enalapril, Lisinopril): ACEI

are potent anti-hypertensive drugs. Their use in late pregnancy has been associated with foetal
toxicity including intrauterine renal insufficiency. Reports of neonatal hypotension, oliguria with
renal failure and hyperkalemia have been reported with ACEI use in pregnancy. Complications
of the oligohydramnios (i.e., foetal limb contractures, lung hypoplasia and craniofacial
anomalies), prematurity, intrauterine growth retardation and foetal death have also been
reported with the use of these agents in late pregnancy.

3. Carbamazepine:Exposure to carbamazepine in utero carries 1% risk of neural tube defects. A

pattern of malformations similar to those described with the foetal hydantoin syndrome has also
been associated with carbamazepine exposure in pregnancy.

4. Coumarin anticoagulants:First trimester exposure to coumarin derivatives is associated with a

characteristic pattern of malformations termed as the ‘foetal warfarin syndrome’. Clinical features
consist of nasal hypoplasia and calcific stippling of the epiphyses, intrauterine growth
 retardation, developmental delay due to central nervous system damage as well as
haemorrhage, eye defects and hearing loss. The critical period of exposure for the foetal
warfarin syndrome appears to be between 6 and 9 weeks of gestation. Oral anticoagulants
readily cross the placental barrier and associated with a high rate of miscarriage.
5. Diethylstilbestrol:Diethylstilbestrol was used in 1950s and 1960s for the diagnosis of the
recurrent miscarriage. Clear cell adenocarcinoma type of cancer of the vagina was found to be
associated with diethylstilbestrol treatment of the patient's mother during the first trimester of
pregnancy.

6. Folic acid antagonists: Aminopterin and Methotrexate

Aminopterin has been known since 1950 to result in foetal death, which led to its use as a
human abortifacient. Malformations include central nervous system defects, facial anomalies
such as cleft palate, high arched palate, ocular hypertelorism, abnormal cranial ossification,
abnormalities in first branchial arch derivatives, intrauterine growth retardation and mental
retardation. Infants have born with features of the aminopterin syndrome after pregnancy due to
methotrexate exposure.

7. Hydantoins (Phenytoin and Trimethadione):Hydantoins have been associated with a

recognizable pattern of the malformation termed as the foetal hydantoin syndrome. The clinical
features include craniofacial dysmorphology i.e. ocular hypertelorism, metopic ridge, broad
depressed nasal bridge, short anteverted nose, bowed upper lip, cleft lip, cleft palate, hypoplasia
of the distal phalanges and nail hypoplasia. Growth retardation, mental deficiency and cardiac
defects are additional features of the syndrome.

8. Misoprostol:Misoprostol is a synthetic prostaglandin E1 analogue, prescribed for duodenal and

gastric ulceration, also used as an abortifacient by the women in Brazil. The association
between first trimester exposure to misoprostol and limb defects with or without Moebius'
sequence has established to certain extent.

9. Antibiotics: Aminoglycosides antibiotics exhibit 2% increased risk for hearing impairment.

Tetracycline and Doxycycline can cause yellow-brown staining of the teeth when used during 4-
9th month of pregnancy timing,when the deciduous teeth begin to calcify. If this medication is
used in the 3rd trimester, there can be decreased foetal bone growth.

10. Valproate: First trimester exposure to the valproate is associated with neural tube defects and
carries 1-2% risk of meningomyelocele, primarily lumbar or lumbosacral. An associated pattern
of malformations is termed as the foetal valproate syndrome. The clinical features include narrow
 bi-frontal diameter, high forehead, epicanthal folds, infra-orbital creases, low nasal bridge, mid-
facial hypoplasia, long philtrum, small mouth, cardiovascular defects, long fingers and toes,
hyperconvex fingernails and cleft lip.

11. Lithium:It is used in the treatment of the bipolar disorder. If possible lithium should be withheld
during the first trimester of pregnancy. Cardiovascular malformations, in particular, Ebstein
anomaly and tricuspid atresia, have been related to lithium exposure. Infants exposed in utero to
lithium may experience transient lethargy, cyanosis, poor feeding and poor respiratory efforts
during the early neonatal period. Other defects that have been noted in infants exposed to
lithium in utero include malformations of the CNS, ear and ureter, altered thyroid and cardiac
function as well as congenital goiter.

12. Isotretinoin (13-cis-retinoic acid):Isotretinoin is a synthetic vitamin A derivative, prescribed for

severe cystic acne that has been proven to be a potent human teratogen as well as a
behavioural teratogen when given systemically. The clinical features include craniofacial
anomalies such as narrow sloping forehead, micrognathia, flat nasal bridge, cleft lip, cleft palate
and ocular hypertelorism. Cardiac defects and alterations in central nervous system
development also observed. Risk for associated miscarriage was found to be approximately
40%.

13. Accutane: Accutane is retinoic acid prescribed for treatment of severe acne. This medication is
extremely dangerous; as infants exposed in the first trimester will exhibit abnormalities like
hydrocephalus (i.e. excess fluid in the brain), brain defects, mental retardation, ear or face
abnormalities, heart and limb defects and chronic skin lesions. There is also an increased risk of
miscarriage.

There are also certain drugs having ‘Possible Teratogenic Potential in Humans’ which include:
1. D-penicillamine:High dose treatment of the pregnant woman with the D-penicillamine has been
found to be associated with connective tissue disorders referred to as cutis laxa).

2. Methimazole:Methimazole treatment during pregnancy has been associated with scalp defects
known as aplasia cutis congenital.

3. Diazepam:First trimester exposure to diazepam can lead to a small increase in the incidence of
cleft lip and palate.

4. Antidepressants: With antidepressants, the baby may tend to be more irritable and have
problems in feeding. There can also be premature delivery.
Now, let us understandthe ‘Effects of Teratogens on Embryonic and Foetal Development’ in
detail.

The time during embryogenesis when the foetus is exposed to a potential teratogen is crucial. The
effect produced by a teratogen depends upon the developmental stage in which the foetus is
exposed to it. Three stages of susceptibility may be identified, with these times varying from one
organ system to the another.

The first stage is ‘Predifferentiation Stage’.The time from conception until implantation is known as
the "all or none" period. The embryo is relatively resistant to teratogenic insults during the first few
weeks of life, perhaps 2 weeks after conception in humans. During this stage, large insults to the
embryo are likely to result in death of the conceptus and miscarriage or in intact survival.
Presumably, the explanation is that, at this stage, the embryo is undifferentiated and repair as well
as recovery is possible through multiplication of the still totipotential cells to replace those which
have been lost. If one cell is destroyed, a surviving cell may compensate and able to assume its
function to form normal embryo. Therefore, exposure of embryos to teratogens during the pre-
implantation stage usually does not cause congenital malformations.

The second stage isreferred to as ‘Embryonic Stage’.The embryonic period from 18 to 60 days
after conception is the period of organogenesis i.e. the process of organ differentiation occurs in
most human organ systems between embryonic weeks 3 to 8. This is the period of maximum
sensitivity to the teratogens, since not only are tissues differentiating rapidly but damage to them
becomes irreparable. Exposure to teratogenic agents during this period has the greatest likelihood
of causing a structural anomaly. Teratogens act in an organ-specific fashion; a teratogen may affect
one organ system at one stage of development but another system at another stage. The pattern of
anomalies produced depends upon which systems are differentiating at the time of teratogenic
exposure. For example, development of the brain and gonads continues in the second and third
trimesters of pregnancy. Therefore, drug use at this time in pregnancy is a concern. Some of the
uterine anomalies resulting from diethylstilbestrol occurred with exposure as late as 20 weeks but
were not recognized until after puberty.

The third stage is the final ‘Foetal Stage’. The foetal phase, from the end of the embryonic stage to
term, is the period when growth and functional maturation of the organs and systems already
formed occurs. Teratogen exposure in this period will affect foetal growth; for e.g., intrauterine
growth retardation, the size of a specific organ, or the function of the organ, rather than cause gross
structural anomalies. Of particular interest is the potential effect of the psychoactive agents (e.g.,
antidepressants, antiepileptics, alcohol and other drugs of abuse) on the developing central nervous
system, which has led to a new field of the behavioural teratology.

Recent findings of teratology suggest that,the classification of a drug as A, B, C, D, or X provides a

guideline to expecting mother for making determinations about using drugs during pregnancy: for
example, class A drugs are deemed always safe, whereas class X drugs have proven to be
damaging to the foetus and teratogenic in nature.

SUMMARY
Now, let us quickly summarize today’s lecture. In this programme of developmental biology, we
have learnt about ‘Teratogenesis’ as an essential element of implications of embryology.

Initially, we have gained the information about different terminologies related to teratology. We have
also learnt various principles of teratogenesis one by one. Along with these, we have also got an
overview of different causes of teratogenesis. Not only these, we have also focused on the
classification of four different types of teratogens as physical agents, infectious agents, maternal
metabolic conditions and various chemicals as well as drugs along with appropriate examples
including malformations induced by them. At last, we have acquired detailed understanding of
different stages of embryonic and foetal development and effects of teratogens on them.

Hope! This lecture will provide adequate knowledge to people in the world about teratogens and
their serious health effects and in turn, help in spreading awareness about avoiding their adverse
exposure.