Abstract
Cadmium (Cd) is a toxic metal widely distributed in the environment. It was reported that maternal blood Cd levels during pregnancy are positively associated with the risk of early preterm birth. Hypertensive disorders of pregnancy (HDP) are major causes of premature births. The placenta is formed through the proliferation and differentiation of cytotrophoblast cells into extravillous trophoblast (EVT) and syncytiotrophoblast (ST) cells, and then EVT migrates and invades to the uterus. Our previous work showed that exposure to low concentrations of Cd inhibited only EVT differentiation and inhibited the migration and invasion of HTR-8/SVneo, EVT-like cells. The study also revealed that the longer the duration of Cd exposure, the more EVT dysfunction was observed even at low concentrations. Several pathways are known to be involved in migration and invasion, including PI3K/Akt signaling pathway. Here, we showed that Cd decreased the phosphorylation levels of AKT and in the long Cd exposure cells, the expression levels of CCN2 were decreased. CCN2, also known as connective tissue growth factor, is a protein belonging to the cellular communication network (CCN)-family of secreted extracellular matrix-associated proteins. It has been reported that CCN2 activates AKT. These results suggest that Cd inhibits the migration and invasion of HTR-8/SVneo cells through regulating PI3K/AKT signaling pathway. We are conducting further studies to determine whetherCd also affects other pathways.
