A note on teratogenesis or congenital deformations.

1. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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Teratogenesis
Teratogenesis is a process that causes birth defects or malformations in an embryo or
foetus (due to environmental factors). OR Teratogens are exogenous (outside the body)
agents that cause birth defects. OR Teratology is the study of the causes and
underlying mechanisms leading to birth defects or malformations.
Most teratogens produce their effects during certain critical periods of development.
Human development is usually divided into two periods:
 Embryonic period (to the end of week 8), when most of the organ systems form.
 Fetal period (the remaining time in the uterus), when growth and modeling occur.
The period of maximum susceptibility (risk of being attacked) to teratogens is between
weeks 3 and 8 since that is when most organs are forming. The nervous system,
however, is constantly forming and remains susceptible throughout development.
Before week 3, exposure to teratogens does not usually produce congenital (by birth)
abnormalities because a teratogen encountered at this time either damages most or all
of the cells of an embryo, resulting in its death, or kills only a few cells, allowing the
embryo to fully recover.
Some Important Teratogens
Some important teratogens include alcohol, retinoic acid, endocrine/hormone disruptors,
synthetic chemicals, heavy metals, and pathogens, etc.
1. Alcohol:
The most devastating teratogen is alcohol (ethanol). Fetal alcohol syndrome (FAS) is a
common syndrome of birth defects in the children of alcoholic mothers. Babies with FAS
are characterized by their small head size. The brain of such a child may be
dramatically smaller than normal and often shows a lack of development. Individuals

2. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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with FAS have a lower IQ than normal; adults with FAS have difficulty learning from
experience.
Another term fetal alcohol spectrum disorder (FASD) is used to encompass all of the
alcohol-induced malformations. In many FASD manifestations, behavioral abnormalities
exist without any physical changes in head size or notable reductions in IQ.
The amount and timing of fetal alcohol exposure, as well as the genetic background of
the fetus, contribute to the developmental outcome, i.e. variability in the metabolism of
alcohol by the mother can be a factor (genetic).
Even a single time consumption of two alcoholic drinks during pregnancy may lead to
loss of fetal brain cells. Importantly, alcohol can cause permanent damage to an unborn
child at a time before most women even realize they are pregnant.
2. Retinoic acid:
Retinoic acid (RA) is a vitamin A derivative that is important in specifying the anterior-
posterior axis and informing the jaws and heart of the mammalian embryo.
In normal development, RA forms gradients (the relative amount of RA informs the cells
of their respective positions along the axis). RA is secreted from particular cells,
diffuses, and is then degraded by other cells. However, if RA is present in large
amounts, the gradient is disturbed, and cells that normally would not receive high
concentrations of this molecule are exposed to it and will respond to it.
The medicinal form of retinoic acid is useful in treating severe cystic acne (skin
disease). There are certain harmful effects of administering large amounts of vitamin A
or its derivatives (i.e. RA) to pregnant animals. The drug now carries a strong warning
against its use by pregnant women.

3. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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A study was conducted on a group of women who accidentally (without knowing)
exposed themselves to retinoic acid but decided to remain pregnant. Of their 59 fetuses:
 26 were born without any noticeable abnormalities.
 12 aborted spontaneously.
 21 were born with obvious abnormalities, i.e. absent or defective ears, absent or
small jaws, cleft palate, aortic arch abnormalities, thymic deficiencies, and
abnormalities of the central nervous system.
Thus, even a compound involved in normal metabolism can have deleterious (harmful)
effects if it is present in large enough amounts and/or at particular times.
3. Endocrine/Hormone Disruptors:
Endocrine disruptors are exogenous (coming from outside the body) chemicals that
interfere with the normal functions of hormones and consequently disrupt development.
These are hormonally active substances that are present in the environment. The
phenotypic changes produced by endocrine disruptors are not very obvious (cannot be
observed). Rather, the anatomical changes induced by endocrine disruptors are often
seen only microscopically, and the major changes are physiological. These compounds
have other names as well: hormone mimics, environmental signal modulators,
environmental estrogens, or hormonally active agents.
These chemicals can interfere with hormonal functions in many ways:
 They can mimic the effect of a natural hormone and bind to its receptors.
 They can inhibit the binding of a hormone to its receptor or block the synthesis of a
hormone.
 They can affect the synthesis, elimination, or transportation of a hormone in the
body.

4. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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 Some endocrine disruptors can prepare the organism to be more sensitive to
hormones later in life.
Hormone disruptors are everywhere in our technological society (and even in rural
areas where pesticides and herbicides are abundant), and that low-dose exposure can
be enough to produce significant disabilities later in life. Endocrine disruptors include
chemicals that line baby bottles and the brightly colored plastic containers from which
we drink our water; chemicals used in cosmetics, sunblocks, and hair dyes, etc.
4. Synthetic Chemicals:
Pesticides and organic mercury compounds have caused neurological and behavioral
abnormalities in infants whose mothers have ingested them during pregnancy.
Moreover, drugs that are used to control diseases in adults may have deleterious
effects on fetuses.
5. Heavy Metals:
Heavy metals such as zinc, lead, and mercury are powerful teratogens. Industrial
pollution has resulted in high concentrations of heavy metals in the environment in
many places. Contamination is more severe where mining interests have been allowed
to dispose of metal-containing slag into streams feeding the lakes.
Lead and mercury can damage the developing nervous system. The polluting of
Minamata Bay, Japan, with mercury in 1956 produced brain and eye deficiencies both
by transmission of the mercury across the placenta and by its transmission through
mother's milk.
6. Pathogens:
Viruses and other pathogens can also act as teratogens. It was reported that women
who contracted rubella virus (German measles) during the first trimester of their

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pregnancy had a 1 in 6 chance of giving birth to an infant with eye cataracts, heart
malformations, or deafness.
Bacteria and protists are rarely teratogenic, but some of them are known to damage
human embryos. Toxoplasma gondii, a protist carried by rabbits and cats (and their
feces), can cross the placenta and cause brain and eye defects in the fetus. Treponema
pallidum, the bacterium that causes syphilis, can kill early fetuses and produce
congenital deafness and facial damage in older fetuses.