PFOA evokes extracellular Ca²⁺ influx and compromises progesterone-induced response in human sperm

Perfluorooctane acid (PFOA), a persistent organic pollutant, is ubiquitously present in the environment and may detrimentally affect male reproductive health. In this study, mature human sperm were in vitro exposed to different concentrations of PFOA (0.25, 2.5 or 25 μg/ml) alone or in combination with progesterone (P4) to evaluate the toxicity and the potential mechanism of action. Exposure to high-dose PFOA (25 μg/ml) alone for 4 h caused a decline in capacity of human spermatozoa to penetrate synthetic mucus, with an increased production of reactive oxygen species (ROS). Furthermore, PFOA treatment (2.5 and 25 μg/ml) evoked a transient rise in intracellular calcium concentration [Ca²⁺]_i by activating the sperm-specific CatSper channel. However, preincubation with PFOA (2.5-25 μg/ml) for 4 h significantly suppressed P4-stimulated extracellular Ca²⁺ influx in human spermatozoa. Moreover, PFOA pretreatment at all concentrations evaluated markedly compromised P4-induced acrosome reaction and sperm penetration into viscous medium. Taken together, these results suggest that PFOA exposure may impair human sperm function through inducing oxidative stress and disturbing P4-induced Ca²⁺ signaling.