Zinc pyrithione induces immobilization of human spermatozoa and suppresses the response of the cAMP/PKA signaling pathway

Abstract

Zinc pyrithione (ZPT), a zinc coordination complex, is used as an antimicrobial agent. This study investigated the molecular mechanisms underlying ZPT-induced spermatozoa immobilization by examining plasma membrane integrity, mitochondrial dysfunction, and the cAMP/PKA signaling pathway response. ZPT inhibited spermatozoa motility and movement patterns in a concentration-dependent manner. The 100% effective concentration (EC₁₀₀) and median effective concentration (EC₅₀) at which ZPT-induced spermatozoa immobilization at 20 s were 40 μmol/L and 16.19 μmol/L, respectively. ZPT did not significantly disrupt spermatozoa plasma membranes, but it exerted a strong and significant effect on the depolarization of mitochondria. In addition, ZPT exposure induced intracellular H⁺ accumulation and Ca²⁺ dissipation in spermatozoa, accompanied by suppression of the cAMP/PKA signaling pathway. Thus, ZPT induces spermatozoa immobilization without significant plasma membrane injury and so could be a candidate microbicidal spermicide.

Keywords: Immobilization; Spermicide; Zinc pyrithione; cAMP/PKA signaling pathway.