This document discusses teratogenesis, which refers to structural or functional defects in a developing embryo or fetus caused by environmental factors. It identifies several categories of teratogens, including drugs/chemicals, ionizing radiation, infections, and pollutants. Specific teratogens are mentioned such as alcohol, retinoic acid, and rubella virus. The timing and amount of exposure to a teratogen, as well as genetics, influence the risk of prenatal defects. The study of teratogenesis is called teratology.
2. Teratogenesis
• Teratogenesis is a prenatal toxicity
characterized by structural or functional
defects in the developing embryo or fetus. It
also includes intrauterine growth retardation,
death of the embryo or fetus, and
transplacental carcinogenesis (in which
chemical exposure of the mother initiates
cancer development in the embryo or fetus,
resulting in cancer in the progeny after birth).
3. Factors influencing prenatal
risks
• The timing of the exposure
• The amount of exposure
• The number of teratogens
• Genetics
• Being male or female.
5. Teratology
• The study of factors that contribute to birth
defects is called teratology.
• Teratogens are environmental factors that can
contribute to birth defects, and include some
maternal diseases, pollutants, drugs and
alcohol.
6. The fates of 20 hypothetical human eggs in
the United States and western Europe.
Under normal conditions, only 6.2 eggs of
the original 20 would be expected to develop
successfully to term.
7. Some agents thought to cause disruptions in human
fetal development
DRUGS AND CHEMICALS IONIZING RADIATION (X-RAYS)
Alcohol HYPERTHERMIA
Aminoglycosides (Gentamycin) INFECTION MICROORGANISMS
Aminopterin Coxsackie virus
Antithyroid agents (PTU) Cytomegalovirus
Bromine Herps simplex
Cigarette smoke Parvovirus
Cocaine Rubella (German measles)
Cortisone Toxoplasma gondii (toxoplasmosis)
Diethylstilbesterol (DES) Treponema Pallidum (syphilis)
Diphenylhydantoin METABOLIC CONDITIONS IN THE MOTHER
Heroin Autoimmune disease (including Rh incompatibility)
Lead Diabetes
Methylmercury Dietary deficiencies, malnutrition
Penicillamine Phenylketonuria
8. Retinoic acid as a teratogen
• In some instances, even a compound that is involved in
normal development can have deleterious effects if
present in large amounts at particular times. Retinoic
acid is important in forming the anterior-posterior axis
of the mammalian embryo and also in forming the
limbs .
• In these instances, retinoic acid is secreted from
discrete cells and works in a small area. However, if
retinoic acid is present in large amounts, cells that
normally would not receive such high concentrations of
this molecule will respond to it.
10. Alcohol as a teratogen
• In terms of frequency and cost to society, the most
devastating teratogen is undoubtedly ethanol. In 1968,
Lemoine and colleagues noticed a syndrome of birth
defects in the children of alcoholic mothers. This fetal
alcohol syndrome (FAS) was also noted by Jones and
Smith (1973).
• Babies with FAS were characterized as having small
head size, an indistinct philtrum (the pair of ridges that
runs between the nose and mouth above the center of
the upper lip), a narrow upper lip, and a low nose
bridge. The brain of such a child may be dramatically
smaller than normal and often shows defects in
neuronal and glial migration.
11. Comparison of a brain from an infant with fetal alcohol
syndrome (left) with a brain from a normal infant of the
same age (right). The brain from the infant with FAS is
significantly smaller, and the pattern of convolutions is
obscured by glial cells that have migrated over the top of
the brain. (Photographs courtesy of S. Clarren.)
12. Alcohol as a teratogen
• A mouse model system has been used to explain the effects
of alcohol on the face and nervous system. When mice are
exposed to ethanol at the time of gastrulation, it induces the
same range of developmental defects as in humans.
• Studies on these mice suggest that ethanol may induce its
teratogenic effects by more than one mechanism.
• First, anatomical evidence suggests that neural crest
migration is severely impaired.
• Second, ethanol can cause the apoptosis of neurons. One
way it can cause apoptosis is to generate superoxide radicals
that can oxidize cell membranes and lead to cytolysis.
14. Prescription/Over-the-counter
Drugs
• About 70% of pregnant
women take at least one
prescription drug (March of
Dimes, 2016e).
• A woman should not be
taking any prescription drug
during pregnancy unless it
was prescribed by a health
care provider who knows she
is pregnant. Some
prescription drugs can cause
birth defects, problems in
overall health, and
development of the fetus.
15. Illicit Drugs
• Common illicit drugs include cocaine, ecstasy
and other club drugs, heroin, marijuana, and
prescription drugs that are abused. It is
difficult to completely determine the effects of
a particular illicit drug on a developing child
because most mothers who use, use more than
one substance and have other unhealthy
behaviors.
16. Pollutants
• There are more than 83,000 chemicals used in the
United States with little information on the effects
of them during pregnancy. An environmental
pollutant of significant concern is lead poisoning,
which is connected with low birth weight and
slowed neurological development,
• The chemicals in certain pesticides are also
potentially damaging and may lead to birth
defects, learning problems, low birth weight,
miscarriage, and premature birth.
17. Pathogens as teratogenic agents
• Another class of teratogens includes viruses and
other pathogens. Gregg (1941) first documented
the fact that women who had rubella (German
measles) during the first third of their pregnancy
had a 1 in 6 chance of giving birth to an infant
with eye cataracts, heart malformations, or
deafness. This was the first evidence that the
mother could not fully protect the fetus from the
outside environment. The earlier the rubella
infection occurred during the pregnancy, the
greater the risk that the embryo would be
malformed.
18. Ionizing radiation
• Ionizing radiation can break chromosomes and
alter DNA structure. For this reason, pregnant
women are told to avoid unnecessary X-rays,
even though there is no evidence for
congenital anomalies resulting from diagnostic
radiation (Holmes 1979). Heat from high
fevers is also a possible teratogen.
20. The Environmental Regulation of
Development
• The environment can affect development in
several ways. Development is sometimes cued
to normal circumstances that the organism can
expect to find in its environment. The larvae of
many species will not begin metamorphosis
until they find a suitable substrate. In other
instances, symbiotic relationships between two
or more species are necessary for the complete
development of one or more of the species.