It was previously believed that the mammalian embryo developed in the impervious uterus of the mother, protected from all extrinsic factors. However, after the thalidomide disaster of the 1960s, it became apparent and more accepted that the developing embryo could be highly vulnerable to certain environmental agents that have negligible or non-toxic effects to adult individuals.
It is estimated that 10% of all birth defects are caused by a prenatal exposure or teratogen.These exposures include, but are not limited to, medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Teratogen-caused birth defects are potentially preventable.
Studies have shown that nearly 50% of pregnant women have been exposed to at least one medication during gestation.An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.
علم التشوهات الجنينيه بدا الاهتمام بيه بعد ملاحظه الاثار السلبيه التى حدثت نتيجه استخدام عقار يدعى thalidomide
It was the major couse of apperance of teratology science
It was used for morning sickness in pregnancy
as sedative-hypnotic and multiple myeloma medication
The drug is a potent teratogen in rabbits and primates including humans: severe birth defects may result if the drug is taken during pregnancy
Thalidomide was sold in a number of countries across the world from 1957 until 1961 when it was withdrawn from the market after being found to be a cause of birth defects in what has been called "the biggest medical tragedy of modern times".
It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000
Since then thalidomide has been found to be a valuable treatment for a number of medical conditions and it is being prescribed again in a number of countries, although its use remains controversial
The thalidomide tragedy led to much stricter testing being required for drugs and pesticides before they can be licensed
phochomelia ( shortening of limbs = sealed limbs occur mainly in arms > legs
amelia (no limbs)
internal malformation in eye & face
The mechanism of thalidomide's teratogenic action
Thalidomide intercalates (inserts itself) into DNA in G-C (guanine-cytosine) rich regions
Due to its glutarimide part, (S) thalidomide fits neatly into the major groove of DNA at purine sites . Such intercalation impacts upon the promoter regions of the genes controlling the development of limbs, ears, and eyes such as IGF-I and FGF-2. These normally activate the production of the cell surface attachment integrin αvβ3 with the resulting alphavbeta3 integrin dimer stimulating angiogenesis in developing limb buds. This then promotes the outgrowth of the bud (IGF-I and FGF-2 are also both known to stimulate angiogenesis). Therefore, by inhibiting the chain of events, thalidomide causes the truncation of limb development. In 2009 this theory received strong support, with research showing "conclusively that loss of newly formed blood vessels is the primary cause of thalidomide teratogenesis, and developing limbs are particularly susceptible because of their relatively immature, highly angiogenic vessel network."
Recently thalidomide may have an effect on immune system : the effect on blood vessels ( angiogenesis ) so thalidomide may be used in treatment of diabetes,HIV. Arthritis
contraindicated in pregnancy