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 m echanism of Cd perturbation of Ca transport, we used JEG-3, a human ch oriocarcinoma cell line which exhibits trophoblastic properties, to an alyse Cd effects in vitro. Treatment with Cd at low, physiologically r elevant concentrations (e.g. 0.04 mu M) did not result in obvious chan ges in cell morphology or integrity, whereas higher concentrations (gr eater than or equal to 0.16 mu M) affected cell integrity. With lower concentrations of Cd treatment for 24 h, activities of cellular Ca upt ake and transport, and Ca2+ binding were decreased, and intracellular [Ca2+] ([Ca2+]i) profile was also altered; however, membrane-associate d Ca2+-activated ATPase activity remained relatively unchanged. Intere stingly, 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 Ca2+-binding protein (H CaBP) was drastically reduced. These results strongly suggest that Cd exposure significantly compromises the Ca handling ability of trophobl astic cells; this effect is probably not due to perturbations in Ca ch annel or membrane Ca pump activities, but rather a consequence of alte rations in subcellular, cytosolic Ca2+ binding activities. (C) 1997 W. B. Saunders Company Ltd.