Perfluorooctane sulfonate and perfluorooctanoic acid inhibit progesterone-responsive capacitation through cAMP/PKA signaling pathway and induce DNA damage in human sperm

Abstract

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two persistent organic pollutants harmful to human health. They induce negative effects on male reproduction by influencing male hormones, spermatogenesis, and sperm quality. However, their effects and mechanisms on human sperm capacitation and fertilization remain unclear. Here, human sperm were incubated with different concentrations of PFOS or PFOA with progesterone during capacitation. Both PFOS and PFOA inhibited human sperm hyperactivation, sperm acrosome reaction, and protein tyrosine phosphorylation levels. PFOS and PFOA decreased intracellular Ca²⁺ concentration in the presence of progesterone, and subsequently decreased cAMP level, and PKA activity. PFOS and PFOA increased reactive oxygen species production and sperm DNA fragmentation during the only 3 h capacitation incubation. Conclusively, PFOA and PFOS may inhibit human sperm capacitation via the Ca²⁺-mediated cAMP/PKA signaling pathway in the presence of progesterone, and induce sperm DNA damage through increased oxidative stress, which is not conducive to fertilization.

Keywords: Acrosome reaction; Capacitation; Human sperm; Hyperactivation; PFOA; PFOS.