BIOCHEMISTRY OF TERATOGENESIS

Teratology is the science of birth defects caused by radiation, viruses, and chemicals, including drug.  Xenobiotic chemical species that cause birth defects are called teratogens.  Teratogens affect developing embryos adversely, often with remarkable specificity in regard to effect and stage of embryo development when exposed.  A teratogen may cause a specific effect when exposure occurs on a definite number of days after conception; if exposure occurs only a few days sooner or later, no effect, or an entirely different one, may be observed.  Although mutations in germ cells (egg or sperm cells) may cause birth deffects (e.g. Down’s syndrome), teratology usually deals with defects arising from damage to embryonic or fetal cells.

The biochemical effects of teratogens are varied and, for the most part, not well understood.  In some cases teratogens interfere with DNA synthesis.  Teratogens may alter the function of nucleic acids in cell replications, and adverse effects may result.  Serious defects may arise from either an absence or excess of chromosomes caused by exposure to xenobiotics, an effect that sometimes can be revealed by microscopic examination.  Enzyme inhibition by xenobiotics can be teratogenic.  Xenobiotics that deprive the fetus of essential substrates (for example, vitamins), that interfere with energy supply, or that alter the permeability of the placental membrane may all cause birth defects.

Perhaps the most notorious teratogen is thalidomide, a sedative-hypnotic drug used in Europe and Japan in 1960-1961.  Some infants born to women who had taken thalidomide from days 35 through 50 of their pregnancies were born suffering from amelia or phocomelia, the absence or severe shortening, respectively, of the limbs.  About 10,000 children were affected.

In 1988 the U.S. Food and Drug Administration estimated that Accutane (retionic acid) used as an anti-acne medication may have been responsible for approximately 1,000 birth defects in children born to women taking the drug during the period 1982-1986.  Exposure of the fetus to the drug over a period of only several days can result in birth defects such as severe facial malformations, heart defects, and mental retardation.

For further information :

Manahan, Stanley E.; Toxicological Chemistry;