Cadmium inhibits motility factor-dependent migration of human trophoblast cells.

The occurrence of intrauterine growth retardation (IUGR) is higher in infants born to mothers exposed to cadmium (Cd2+) through environmental sources such as smoking and industrial work. A contributing factor of IUGR is improper placentation. The human placenta is established through the function of a specialized group of cells known as extravillous trophoblast (EVT). Paramount among the abilities of these cells is the capacity to migrate and invade into the endometrial wall of the uterus in order to anchor the placenta and access the maternal blood supply. EVT cell migration is regulated by interactions of a number of autocrine and paracrine factors with their respective receptors on the trophoblast. In order to investigate potential involvement of environmental exposure relevant concentrations of Cd2+ exposure on placental function, we measured the effects of 0.5-1 μmol/L CdCl2 on cellular migration in an immortalized human trophoblast cell line, HTR-8/SVneo. We found that these concentrations of CdCl2 kept the cells viable until at least 48 h and didn't affect basal migratory capacity but eliminated cell migration induced by IGF-II, or PGE2 or uPA-ATF. In addition, the presence of CdCl2 resulted in filamentous actin disorganization of the trophoblast cells. However, pre-incubations of the cells with zinc-chloride (ZnCl2), or caspase inhibitor (CI-1) resulted in reversal of ligand-dependent cellular migration and actin disorganization. These findings suggest that low concentrations of Cd2+, though do not affect trophoblast cell survival can interfere with ligand-induced trophoblast cell migration by affecting actin cytoskeletal organization possibly through activation of caspase(s).