Induction of neural tube defects and skeletal malformations in mice following brief hyperthermia in utero.

Hyperthermia was induced in ICR mice on day 8.5 of gestation by immersing them in hot water. Control mice were immersed in water at 38 degrees C for 15 min. In dams exposed to 42 degrees C for 12.5-15 min or to 43 degrees C for 7.5-10 min, externally malformed fetuses increased significantly and in a dose-related manner. Anterior neural tube defects (exencephaly, anencephaly, encephalocele, and cranial neural tube defect with facial cleft) were induced most frequently. Embryonic and fetal death and skeletal malformations also increased following heat stress. At intervals after heat exposure, sections of embryonic prosencephalon were prepared for light microscopy. At 2 h after heat stress, mitotic figures disappeared almost completely in embryonic tissues. Mitotic activity was inhibited for at least 3 h. At 6 h, there was a burst of new mitotic activity. Some damaged cells became pyknotic and abnormal cells were encountered in the neuroepithelial tissue after 3-12 h. 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.