Functional consequences of prenatal methylmercury exposure: effects on renal and hepatic responses to trophic stimuli and on renal excretory mechanisms.

The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions of urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. In addition, the reactivity of the kidney to challenge with desmopressin was altered coincidentally with the appearance of the effects on basal clearance mechanisms. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs. postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology