Mitotic arrest in the developing CNS after prenatal exposure to methylmercury.

Methylmercury is toxic to both the mature and the developing nervous system. One mechanism of its effects on the developing neonatal cerebellum is its interference with cell production by mitotic arrest. To investigate whether this mechanism is active in the prenatal CNS, fetuses exposed to methylmercury were compared to control fetuses 24 hours or 48 hours after an 8 mg/kg dose to their dams. By the first sacrifice time, levels of Hg203 in fetuses approached the level in the dam, and by the second sacrifice time methylmercury-exposed fetuses weighed significantly less than controls. Four regions of the developing brain were studied to evaluate methylmercury effects on mitotic activity. General measures such as mitotic index, number of proliferative cells, and thickness of the proliferative zone were not reduced by treatment in any region at either sacrifice time. In contrast, each region showed evidence of methylmercury effects on the pattern of mitosis. Exposed fetuses had increased numbers of early mitotic figures, decreased numbers of late mitotic figures, or a decrease in the proportion of cells reaching late mitosis. Thus, neurons produced during gestation, like those produced postnatally, appear to be sensitive to methylmercury's antimitotic action. Whether the arrest of these cells leads to a permanent reduction in neuron number, as it does in neonates, remains to be investigated.