Comparison of some biochemical effects of teratogenic doses of mercuric mercury and cadmium in the pregnant rat

Abstract

Mercuric mercury (Hg²⁺), like cadmium (Cd²⁺), interferes with the transport of certain essential metals to the conceptus in the pregnant Wistar rat and, at 48 h after the IV injection of a teratogenic dose (0.79 mg Hg²⁺/kg body weight) on day 12 of gestation, the foetal concentrations of Zn²⁺, Cu²⁺ and Fe³⁺, but not of Mg²⁺, are reduced significantly. Both Hg²⁺ and Cd²⁺, at teratogenic dose levels, inhibit the placental and foetal uptake of ⁶⁵Zn²⁺ and ⁶⁷Cu²⁺, but possibly by different mechanisms. In addition, the effects of Hg²⁺, at different times after dosing, on the uptake of these labelled tracers and of ⁵⁹Fe³⁺, administered as 15-min pulses, do not parallel the changes in the placental and foetal concentrations and contents of the endogenous, stable metallic ions. The teratogenic dose of Hg²⁺ inhibits the placental and foetal uptake of L-[4,5-³H]-leucine, but not the incorporation of the labelled amino acid into foetal protein. In contrast, the corresponding dose of Cd²⁺ inhibits both leucine uptake and protein synthesis in the placenta and foetus. Similarly, Cd²⁺ inhibits the uptake of [2-¹⁴C]-thymidine and its incorporation into foetal DNA, whereas Hg²⁺ reduces the placental and foetal uptake, but has little or no effect on the utilization of the nucleoside. Since both Cd²⁺ and Hg²⁺ reduce the foetal uptake of ⁶⁵Zn and the foetal concentration of Zn, but only Cd²⁺ interferes with DNA synthesis, it is unlikely that the inhibition of the metabolism of thymidine can be attributed to reduction in thymidine kinase activity in consequence of foetal Zn deficiency. It is concluded that the small amount of Cd²⁺ that is taken up by the foetus has a direct effect on the synthesis of DNA and protein, whereas Hg²⁺ primarily affects placental transport processes.