Visceroatrial heterotaxy syndrome induced by maternal hyperthermia in the rat

Summary Maternal hyperthermia induces malformations in human and laboratory animals, but there are only a few reports of cardiovascular anomalies induced by maternal hyperthermia. Pregnant Wistar Imamichi rats were exposed to hyperthermia on day nine of gestation by immersion in a hot-water bath (43.0–43.5 °C) twice a day. Their fetuses were examined on day 18 after fixing with 2.5% glutaraldehyde solution. According to the average body temperature of the dam, the fetuses were divided into five groups, each group increasing by 0.1 °C from 42.5 °C to 42.9 °C. The incidence of cardiovascular anomalies was increased from 24 to 100% with the rise in body temperature of the dams. In the groups with average temperatures of 42.8 and 42.9 °C, most of the fetuses (70–80% of cases with anomalies) showed visceroatrial heterotaxy associated with severe cardiovascular anomalies, including common atrioventricular orifices with double outlet right ventricle or discordant ventriculo-arterial connections. The visceral structures of those fetuses showed a tendency to left isomerism, such as bilateral left atrial appendages, single lobation of the lung on both sides, a symmetrical liver with interruption of the posterior caval vein, hypoplasia of the spleen, and malrotation of the intestinal loop. Day nine of gestation in the rat may be a critical period for determining left-right sidedness of the viscera. The results indicate that the determination of morphological left-sidedness of visceral structures is related in some way with maternal hyperthermia.