Effects of cadmium on trophoblast calcium transport.

Maternal exposure to cadmium (Cd) during pregnancy has been linked to low fetal birthweight, which may be attributed to placental damage and/or dysfunction in nutrient transport. Previous studies have suggested that Cd is accumulated in the placenta, and that placental transport of calcium (Ca) and zinc (Zn) is perturbed by Cd. To investigate the mechanism of Cd perturbation of Ca transport, we used JEG-3, a human choriocarcinoma cell line which exhibits trophoblastic properties, to analyse Cd effects in vitro. Treatment with Cd at low, physiologically relevant concentrations (e.g. 0.04 microM) did not result in obvious changes in cell morphology or integrity, whereas higher concentrations (> or = 0.16 microM) affected cell integrity. With lower concentrations of Cd treatment for 24 h, activities of cellular Ca uptake and transport, and Ca2+ binding were decreased, and intracellular [Ca2+] ([Ca2+]i) profile was also altered; however, membrane-associated Ca(2+)-activated ATPase activity remained relatively unchanged. Interestingly, cellular Ca uptake activity was unaffected by short-term (30 min) Cd pretreatment. The 24-h Cd treatment also resulted in elevated expression of the metal-binding protein, metallothionein, whereas the expression of a trophoblast-specific cytosolic Ca(2+)-binding protein (HCaBP) was drastically reduced. These results strongly suggest that Cd exposure significantly compromises the Ca handling ability of trophoblastic cells; this effect is probably not due to perturbations in Ca channel or membrane Ca pump activities, but rather a consequence of alterations in subcellular, cytosolic Ca2+ binding activities.