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Teratogenesis- Environmental
Assaults on Human
Development
Submitted By- Aiman Jahangir, Neha,
Deepanshu
Submitted To- Dr Sonam Grover
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).
Factors influencing prenatal
risks
• The timing of the exposure
• The amount of exposure
• The number of teratogens
• Genetics
• Being male or female.
Critical Periods of Prenatal
Development
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.
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.
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
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.
Teratogenic effect of retinoic acid in
Swiss mice
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.
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.)
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.
Possible mechanisms producing
fetal alcohol syndrome.
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.
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.
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.
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.
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.
Medications
Alcohol
Androgens
Anticonvulsants
Antineoplastics
Cocaine
Diethylstilbestrol
Etretinate
Lodides (including
radioactive iodine)
Isotretinoin
Lithium
Live vaccines
Methimazole
Penicillamine
Tetracyclines
Warfarin
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.
References
• http://www.devbio.com/chap21/link2112.shtml
• http://www.devbio.com/chap21/link2113.shtml
• http://www.devbio.com/chap21/link2111.shtml
• https://courses.lumenlearning.com/suny-
lifespandevelopment/chapter/teratogens/
Teratogenesis- Environmental Assaults on Human Development

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Teratogenesis- Environmental Assaults on Human Development

  • 1. Teratogenesis- Environmental Assaults on Human Development Submitted By- Aiman Jahangir, Neha, Deepanshu Submitted To- Dr Sonam Grover
  • 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.
  • 4. Critical Periods of Prenatal Development
  • 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.
  • 9. Teratogenic effect of retinoic acid in Swiss mice
  • 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.
  • 21. References • http://www.devbio.com/chap21/link2112.shtml • http://www.devbio.com/chap21/link2113.shtml • http://www.devbio.com/chap21/link2111.shtml • https://courses.lumenlearning.com/suny- lifespandevelopment/chapter/teratogens/