Embryonic stress hypothesis of teratogenesis.
Cells and tissues of essentially all eukaryotes respond uniformly to a variety of stressful situations. Immediately following the onset of several types of environmental insult (e.g., hyperthermia), genes for the so-called heat-shock proteins become unusually active; simultaneously, other genetic loci that were engaged in transcription at the onset of the insult become relatively less active. The biologic significance of the heat-shock response is unknown, as is its role, if any, in maintaining human health. In fact, the heat-shock response seems not to have been invoked previously to explain any aspect of human health or disease. Herein, the proposal is made that induction of the heat-shock response in the mammalian embryo during the critical period of organogenesis can alter the established program of activation and inactivation of genetic loci essential for normal intrauterine development, the result being anatomic malformation. By this hypothesis, induction of the heat-shock response provides a common pathway by which diverse environmental agents can result in any of a variety of developmental abnormalities, the precise period during gestation when the response is induced determining the nature of the abnormalities.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D000013:Congenital Abnormalities / Q000209:etiology* / Q000378:metabolism; D004330:Drosophila; D005260:Female; D005333:Fetus / Q000378:metabolism; D005334:Fever / Q000150:complications; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications; D012313:RNA / Q000096:biosynthesis
D006360:Heat-Shock Proteins; D012313:RNA