Depression of metallothionein in fetal rat liver following maternal cadmium exposure

Abstract

Pregnant rats were injected subcutaneously on day 10 of pregnancy with 0.0, 0.25, 0.50, 1.0 or 3.0 mg cadmium/kg and sacrificed at term (day 21). There were no fetal or maternal deaths following the cadmium exposure with the exception of the 3.0 mg/kg level where a 54% fetal mortality rate was observed. At doses of 1.0 mg/kg or less, non-specific parameters of fetal toxicity including body weight, crown-rump length, and liver weight were not significantly different from control values. The same was true of term placental weight as well as maternal weight gain over the 48-h treatment period. Following gel-filtration of hepatic cytosols from control fetuses, over 70% of the endogenous cytosolic zinc was associated with a peak previosly described as metallothionein. It was found that cadmium exposure at sub-lethal doses caused a depression in both total cytosolic zinc and metallothionein-bound zinc levels in the fetus, whereas both these parameters increased in the maternal liver. In vitro cadmium saturation prior to gel filtration revealed that the cadmium-binding capacity of the metallothionein peak was significantly reduced at all dosage levels in the fetus but increased in maternal liver. These findings suggest that maternal administration of cadmium can depress fetal metallothionein levels and cytosolic zinc levels at doses which do not produce overt fetal toxicity. This reduction in fetal metallothionein is in sharp contrast with the well established finding of induction of metallothionein seen in the adult following exposure to cadmium.