Pentachlorophenol inhibits CatSper function to compromise progesterone's action on human sperm.

Pentachlorophenol (PCP), a highly toxic contaminant of chlorophenols, is common in a variety of environments and presents serious risks to animal and human health. However, the reproductive toxicity and potential actions of PCP have not been investigated thoroughly, especially in humans. Here, human spermatozoa were used to evaluate the effect of PCP on cell function and to explore the underlying mechanisms. PCP had no substantive effects on sperm viability or motility, nor on the ability to penetrate viscous medium, sperm hyperactivation or spontaneous acrosome reactions. However, PCP significantly inhibited these properties induced by progesterone (P4). Consistent with the functional observations, although PCP itself did not affect the basal intracellular Ca2+ concentrations and CatSper current, PCP dose-dependently inhibited increases of intracellular Ca2+ concentrations caused by P4. In addition, the activation of CatSper induced by P4 was largely suppressed by PCP. This is the first report showing that PCP may serves as an antagonist of the P4 membrane receptor to interfere with Ca2+ signaling by compromising the action of P4 on regulating sperm function. These findings suggest that the reproductive toxicity of PCP should also be a matter of concern as a mammalian health risk.