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MECHANISM OF ACTION OF TERATOGENIC AGENTS

INTRODUCTION
Teratology is the study of abnormalities of physiological development. It is often thought of as the
study of human birth defects, but it is much broader than that, taking in other non-birth developmental
stages, including puberty; and other non-human life forms, including plants. A newer term
developmental toxicity includes all manifestations of abnormal development, not only frank terata.
These may include growth retardation or delayed mental development without any structural
malformations.
TERATOGENS
Teratogens are toxic agents that cause abnormal development resulting in birth defects. Between 3%
and 5% of children born in the United States are born with developmental defects. Of these, only 2% to
3% of them are classified as teratogen-induced malformations. However, 60-70% of all defects are of
unknown origin. Developmental toxicology is an expanding field and some of the unclassified defects
may eventually be classified as teratogen-induced. Teratogenic substances do not affect each
developing fetus in the same way. The fetus is most at risk during organogenesis (development of
organs), which begins at about three weeks post-conception, and continues until the organs' defining
characteristics have been achieved. The severity and type of the congenital malformation may vary
with the duration of exposure and the specific teratogen. However, exposure to the same substance on
different days in development can produce different defects. Many teratogens are fatal at high doses,
causing miscarriage. Defects that present later, such as growth development and functional
impairment, are harder to relate to teratogen exposure. In the time between birth and detection of
impairment, exposure to other toxicants may have occurred, increasing the difficulty of identifying the
responsible toxicant.
FACTORS INFLUENCING THE EFFECTS OF. TERATOGENS
1. Timing: The effect of a teratogen on the developing organism depends on what period in the
pregnancy (in development) the child is exposed to the teratogen.
A) Some teratogens cause damage only during specific days or weeks in early pregnancy
B). Other teratogens are harmful at any time during the pregnancy, for example, for behavioral
teratogens, there is no safe period, the brain and nervous system can be harmed throughout the
pregnancy
2. Critical period: In prenatal development, the time when a particular organ or other body part is most
susceptible to teratogenic damage
3. Exposure: The effect of a teratogen on the developing organism also depends on the dose and/or
frequency of exposure of/to the teratogen
4. Threshold effect: The phenomenon in which a particular teratogen is relatively harmless in small
doses but becomes harmful when exposure reaches a certain level (the threshold)
5. Interaction effect: The phenomenon in which a particular teratogens potential for causing harm
increases when it is combined with another teratogen or another risk factor
6. Genetic variability: Another factor that determines whether a specific teratogen will be harmful is the
genetic make-up of the developing organism. Possessing and not possessing certain genes may make
the developing child more susceptible to the effect of a teratogen

. 5. precursors or energy sources. or by producing osmolar imbalances. deafness. slow physical growth. and skeletal problems in offspring. including lead and cadmium. Rubella---a viral disease. These birth defects are caused by the mother's drinking excessive quantities of alcohol when pregnant. Other metals. Radiation .Examples of Teratogens A)Diseases (Maternal Illness) 1. either a total absence of some or all limbs or a shortening of the long bones in the arms or legs.Diethylstilbestrol is a synthetic estrogen. aspirin. In addition. 2. and abnormal sleep patterns. as well as other organ deficiencies. Infants may be born addicted and go through withdrawal symptoms included seizures. antacids. Cocaine . Ethanol . heroine.e. 6. female children of women who took DES had an increased risk of rare vaginal cancers and frequently malformed uteruses. TERATOGENIC AGENTS 1.A medication administered to pregnant women in Europe in the 1950s and 1960s. alterations in membrane transport processes. tobacco. tremors. and causes developmental abnormalities. It causes blindness. modifications of the cell surface or matrix that lead to altered cell migration. and retarded mental development.Metals such as methyl mercury increase the risk of cerebral palsy and other neurological disorders. Thalidomide . thalidomide reduced nausea and vomiting during pregnancy. DES . neurological. TERATOGENIC MECHANISMS Modes of action of teratogens Teratogens may act by causing mitotic interference. Thalidomide also caused limb malformations. Cells in a developing embryo are rapidly dividing and are thus more vulnerable to DNA damage. However. marijuana.Cocaine use during pregnancy is associate with premature labor and low birth weight. alcohol. 3.g. It was another drug administered to pregnant women with the intention to reduce miscarriage risk. cocaine. acne medication. those exposed in utero to thalidomide had an increased risk for congenital heart disease.Ionizing radiation breaks both strands of the DNA molecule and causes an alteration in chemical structure of the nitrogenous bases. and other fertility problems. deficiencies in substrates. Male children were likely to have smaller testes and decreased amounts of semen production. diet pills Psychoactive drugs: drugs that affect how the mind works i. if contracted early during pregnancy. This leads to cell death or impaired cell reproduction.All psychoactive drugs slow down fetal growth and increase the risk of premature labor Fetal Alcohol Syndrome (FAS): a cluster of birth defects. alterations in RNA or protein synthesis.. Metals .Ethyl alcohol is associated with Fetal Alcohol Syndrome Disorder (FASD). and damage to the central nervous system B) Drugs (Medications or Social Drugs) Medicinal drugs: These are drugs that remedy problems in a person's body that in some cases have teratogenic effect e. impair the function of enzymes involved in energy production. can harm the fetus. 4. including abnormal facial characteristics. Alcohol consumption during pregnancy can lead to behavioral. tetracycline.

also can cause fetal malformations. A healthy placenta is the mechanism by which the fetus receives nutrition. and cell death from toxic exposure can cause abnormal development by its disruption. In addition. If only few cells die. Maternal and Placental Toxicity: Toxins that affect maternal health or the placenta also affect development. instead inhibiting normal cell function. substances which interfere with apoptosis. and waste is removed. Genotoxicity: Genotoxic substances cause damage to the DNA in a cell. Rubella syndrome) c) Defective cell interactions (lens or kidney agenesis. Examples of teratogenic action a) Increase or decrease in programmed cell death (ectrodactyly) b) Altered mitotic rates (microcephaly. while DNA damage later in development can lead to malformations. Impairment of these functions can lead to cell death. toxic exposures to such substances usually cause congenital malformations rather than miscarriage. the inhibition of cell function has similar effects as cell death. both through cell-to-cell contact and biochemical signals. if large numbers of cells are killed. meromelia) .Cell Death: In the developing fetus. Impaired Cell Function: Some toxic agents do not cause cell death. meromelia) d) Altered cell surface properties (cleft palate. Exposure to toxic substances causing cell death during early pregnancy. gas is exchanged. can result in spontaneous abortion. the embryo can replace the dead cells and continue development. This communication is necessary to synchronize cell differentiation. Such damage frequently leads to cell death and can cause spontaneous abortion. However. In later development. however. communications occur between cells. Maternal infections can result in malformation or miscarriage as well. planned cell death that is part of normal development. Toxoplamsa gondii infection has been associated with head and eye malfomations.

e) Altered morphogenetic movements (Talpid) .