Cadmium effect on zinc metabolism in human trophoblast cells: involvement of cadmium-induced metallothionein

Abstract

Isolated trophoblast cells from human placenta at term were used to investigate the effect of cadmium exposure on the placental transport of zinc. Cells were exposed to cadmium acetate (0–2 μM) for 18 h. These concentrations were found to be non-cytotoxic as determined by protein recovery and the leakage of lactate dehydrogenase. Primary trophoblast cultures showed a cadmium-dependent increase in metallothionein content. After incubation with 65Zn for different times 65Zn contents were compared between control and cadmium-exposed cells. Zinc uptake by the cells after cadmium pre-exposure was increased in a cadmium dose-dependent manner. The additional amount of zinc that was taken up by the cadmium pre-exposed cells with respect to the control cells remained constant during a 30-min incubation of the same cells in a metal-free medium. The cytosol of cadmium-exposed cells showed a higher content of zinc than that of control cells. Most of the zinc in the cytosol is in the metallothionein fraction. We have thus demonstrated that cadmium-induced metallothionein binds zinc in the trophoblast, making this essential element less available to the fetal circulation.