Persistent, differential alterations in developing cerebellar cortex of male and female mice after methylmercury...

Developing animals have long been believed to be more sensitive to methylmercury toxicity than adults, but the reasons for differential effects are not well understood. In the present study, 2-day-old mice received a single per os dose of 4 mg Hg/kg methylmercury and were sacrificed 24 h or 19 days later. This resulted in a mean brain concentration of 1.8 micrograms Hg/g tissue on day 3 and less than 0.1 micrograms Hg/g on day 21. Compared to littermate vehicle controls, the methylmercury-treated mice exhibited a significant reduction in cell numbers in 1 of 4 regions of the developing cerebellar external granular layer 24 h after treatment. Although the mitotic index over the same 4 regions was not significantly altered by methylmercury treatment, the total number of mitotic figures per section of cerebellum was significantly reduced in the treated group. The ratio of late mitotic figures to total mitotic figures was significantly reduced, indicating mitotic arrest. Both of these antimitotic effects were greater in males than females. Cerebellar structure was also examined 19 days after methylmercury treatment. The number of cells in the molecular layer and thickness of the molecular layer and internal granular layer were significantly reduced in males; the number of Purkinje cells in both sexes and all measures in females remained unaltered. This suggests that early cell loss results in persistent reductions in cell number. Although the basis for the differential effect in males and females is not known, the antimitotic effect of methylmercury is most likely the mechanism underlying the reduced cellularity in treated animals.