Experimental study on the embryotoxic effects of hyperthermia and their prevention

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The effects of maternal hyperthermia during pregnancy on pre- and postnatal development of the offspring was investigated in mice.1. Hyperthermia was induced in ICR mice on day 8 of gestation by immersing them in hot water. In dams exposed to 42゜C for 12.5-15 min and to 43゜C for 7.5-10 min, externally malformed fetuses increased significantly and in a dose-related manner. Anterior neural tube defects were induced most frequently. Embryonic and fetal death and skeletal malformations also increased following heat-stress.At intervals after heat exposure, sections of embryonic telencephalon were prepared for light microscopy. Mitotic activity was inhibited for at least 3 hr. Some damaged cells became pyknotic and abnormal cells were encountered in the neuroepithelial tissue after 3-12 hr. Thus, neural tube defects in mouse embryos following maternal hyperthermia may result from a temporary cessation of cell proliferation and partial necrosis of the embryonic neuroepithelium.2. Pregnant ICR … More mice were heat-stressed at 42゜C or 43゜C for 10 min once or twice daily on days 12 through 15 of gestation and the postnatal development of their offspring was observed. Postnatal weight gain of the offspring and their brain weight at 11 weeks of age were smaller than the values for control animals. As compared with controls, prenatally heated mice were hypoactive in an open field and learned slowly in a waterfilled multiple T-maze and in a shuttle box. Thus, prenatal brief hyperthermia in mice was shown to suppress the body and brain growth during the postnatal period and adversely affect their emotionality and learning capacity.3. Pregnant ICR mice were injected with a single dose of 25% ethanol and/or heat-stressed at 42゜C on day 8 of gestation. Combined treatment with ethanol(0.01-0.02 ml/g) and heat (10 min), when they were given concurrently or 1 hr apart, resulted in a significant increase of resorptions and externally malformedfetuses. Skeletal malformations and visceral variations also increased significantly following a cuncurrent exposure to both agents. These results indicate that ethanol and heat can be synergistically teratogenic in mice when the doses of each agent are below the teratogenic threshold. Less