Alleviation of maternal hyperthermia-induced early embryonic death by administration of melatonin to mice.

Maternal hyperthermia induces early embryonic death via increased oxidative stress to the embryo. In this study, we examined whether melatonin administered to heat-stressed pregnant mice would reduce hyperthermia-induced embryonic death. Mice were heat stressed (12 hr at 35 degrees C, 60% relative humidity) on the day of mating and melatonin (3 mg/kg body weight) was injected subcutaneously every 2 hr during heat exposure. Thereafter, zygotes were collected, and in vitro developmental ability and intracellular glutathione (GSH) content were assessed. In addition, reactive oxygen species (ROS) levels and free radical scavenging activity (FRSA) in the oviduct as well as lipid peroxidation in the liver were measured. Melatonin administration was associated with a tendency for higher intracellular GSH content in zygotes (1.67 pmol/zygote) and a significantly higher percentage of embryos that developed to the morula or blastocyst stage (47.91%; P < 0.01) compared with the parameters in heat-stressed mice that were administered a placebo (1.48 pmol GSH/zygote and 14.78% development). Lipid peroxidation levels in the liver and ROS levels in the oviduct were the same in melatonin-treated stressed mice and the controls, while these parameters were significantly higher in heat-stressed mice that were not treated with melatonin. Furthermore, FRSA in the oviduct was significantly (P < 0.05) higher in the melatonin-treated mice than in the controls. These results suggest that administration of melatonin to heat-stressed mice alleviates hyperthermia-induced early embryonic death and that this is accomplished in part by maintaining a neutral redox status within the mother.