Cadmium triggers oxidative stress and mitochondrial injury mediated apoptosis in human extravillous trophoblast HTR-8/SVneo cells

Cadmium (Cd) is a bioaccumulative heavy metal element with potential placental toxicity during pregnancy. Up to now, however, the precise toxic effects of Cd on human placentae, particularly as they pertain to trophoblast cells remain obscure. We therefore sought to investigate the cytotoxic effects of Cd on human extravillous trophoblast HTR-8/SVneo cells and the mechanisms involved in the processes. Results in this present study showed that CdCl2 treatment significantly suppressed cell viability and induced noticeable oxidative stress in HTR-8/SVneo cells. Further studies showed that CdCl2 treatment caused distortion of mitochondrial structure, reduction of mitochondrial membrane potential (Δψm), DNA damage and G0/G1 phase arrest. Under the same condition, CdCl2 treatment increased Bax/Bcl-2 ratios by up-regulating Bax expression and down-regulating Bcl-2 expression, and activated apoptotic executive molecule caspase-3, which irreversibly induced HTR-8/SVneo cell apoptosis. N-acetyl-l-cysteine (NAC), ROS scavenger, significantly attenuated CdCl2-caused mitochondrial injury, DNA damage, G0/G1 phase arrest and apoptosis. In addition, in vivo assay suggested that CdCl2 induced trophoblast cells apoptosis but not other cells in mice placental tissue. Taken together, these data suggest that Cd selectively triggers oxidative stress and mitochondrial injury mediated apoptosis in trophoblast cells, which might contribute to placentae impairment and placental-related disorders after Cd exposure. These findings may provide new insights to understand adverse effects of Cd on placentae during pregnancy.