Effects of maternal stress on methylmercury-induced developmental toxicity in mice

Abstract

The developmental toxicity of combined exposure to maternal restraint stress and methylmercury chloride (MMC) was assessed in Swiss mice. On day 10 of gestation, four groups of plug-positive female mice were treated (p.o.) with a single dose of 12.5 or 25 mg MMC/kg. Immediately after MMC exposure, two of those groups were subjected to restraint for 14 hr. Control groups included restrained and unrestrained pregnant mice nonexposed to MMC. Combined exposure to 25 mg MMC/kg and restraint enhanced MMC-induced maternal toxicity, which included deaths and decreased body weight gain and food consumption. The number of nonviable implants was also increased significantly following concurrent exposure to MMC (25 mg/kg) and restraint, with the percentage of postimplantation loss increased from 64% (MMC alone) to 100% (MMC plus restraint). However, the types and incidence of internal and skeletal anomalies observed after administration of 12.5 mg MMC/kg were not increased by maternal restraint. These results suggest that maternal stress would enhance the MMC-induced maternal and embryo/fetal toxicity at doses of MMC that are highly toxic to the dams, whereas at doses that are less acutely toxic the role of maternal stress would not be significant.