Mechanisms and prevention of developmental brain disorders due to prenatal effects of physical agents

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1. Comparative study of heat-induced teratogenesis in the human and guinea pigHistological studies of human embryos with neural tube defects whose mothers experienced hyperthermic stress early in pregnancy revealed overgrowth, necrosis, vacuolization, rosette formation and cortical derangement in the brain of heated embryos. These histological abnormalities resembled the pathological findings observed in guinea pig fetuses heated in utero. It seems that hyperthermia induces developmental brain abnormalities by common mechanisms in the human and guinea pig. Guinea pigs are born with a rather mature brain and can be a good model of developmental brain disorders in the human.2. Induction of heat-shock proteins and thermotoleranceWhen cultured rat embryos are heated in vitro for 7.5 min at 43ﾟC, neural tube closure is inhibited. If cultured embryos were preheated by subteratogenic heating conditions (e.g., 42ﾟC for 10 min), the incidence of malformed embryos decreased, suggesting that rat embryos can acquire thermotolerance by subteratogenic heating.Several specific heat-shock proteins are induced in rat fetal tissues. When rat fetuses were heated in utero, HSP88, 73 and 71 were increased while HSP73 was decreased. The relationship between the induction of heat-shock proteins and thermotolerance is now under study.3. Vertebral transformation induced by prenatal heat stressPregnant mice were heated in utero on day 7, 8 or 9 of gestation and the skeletons of their fetuses were stained and examined. Anterior and posterior transformations of the axial skeleton were induced depending on the timing of heat stress and the degree of heat elevation. Prenatal heat stress may disturb the expression of homeotic genes and cause abnormal differentiation of the somite.The present studies showed that prenatal heat stress can interfere with the development of the brain and produce various developmental brain disorders.