In vitro exposure of human spermatozoa to bisphenol A induces pro-oxidative/apoptotic mitochondrial dysfunction

Abstract

As bisphenol A (BPA) exerts oxidative/pro-apoptotic effects in several cell types, we explored whether the in vitro exposure to BPA could affect human sperm integrity through the induction of pro-oxidative/apoptotic mitochondrial dysfunction. The exposure of motile sperm suspensions to scalar BPA concentrations for 4h produced a decrease in the mitochondrial membrane potential, starting from 300μM. It was associated with an increased mitochondrial generation of superoxide anion, caspase-9 and caspase-3 activation and motility decrement. Vitality decline was observed at BPA≥400μM. Twenty hours exposure to 300μM BPA, but not to lower concentrations, produced a significant loss in sperm vitality associated with a complete sperm immobilization. Finally, 300μM BPA also produced a significant DNA oxidative damage, as revealed by the formation of oxidized base adduct 8-hydroxy-2'-deoxyguanosine. In conclusion, BPA affected human sperm integrity by inducing pro-oxidative/apoptotic mitochondrial dysfunction.

Keywords: 8OHdG; Apoptosis; Caspase; DNA damage; Flow cytometry; Mitochondrial membrane potential; ROS; Sperm motility; Sperm viability.