Hyperthermia and the induction of neural tube defects in mice

The aim of this study was to examine some parameters determining the teratogenicity of hyperthermia. Pregnant inbred (C57B1/6J and CBA/Ca/T6) and outbred (QS) mice were partially immersed in a water bath at 43-43.5 degrees C until their core temperature, monitored by a rectal thermister probe, was elevated to 43 degrees C for the inbred mice and 43.5 degrees C for the outbred mice. The procedure was repeated 6 h later. The regimen of 2 heatings was performed over a range of development from pregastrulation to about the 24 somite stage. The mice were killed on day 19, and the fetuses were examined. Exencephaly was the common malformation seen in each strain. It occurred at a maximum incidence of 34% in the QS mice, 14% in the CBA strain, and 20% in C57B1 mice. For the CBA and QS mice 4 to 11-15 somites was the most heat sensitive stage of development for the induction of exencephaly while in the C57B1 mice the preceding 24 hr of development were most sensitive. Control mice were exposed to the same experimental procedure in a water bath at body temperature at the most sensitive stage of development for the strain. There were no instances of exencephaly in the controls. The sex of all fetuses was determined and revealed a high female/male ratio among the fetuses with exencephaly (2.1 for the QS mice, 1.7 for the CBA mice, and 3.1 for the C57B1 mice) compared with a ratio of approximately 1.0 for all fetuses. Analysis in the QS mice indicated that the predominance of female exencephalics was probably due to prenatal loss of male embryos.