The toxic effects of Bisphenol A on the mouse spermatocyte GC‐2 cell line: the role of the Ca²⁺‐calmodulin‐Ca²⁺/calmodulin‐dependent protein kinase II axis

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is known to induce male reproductive toxicity in rodents. However, its toxic effects on the germ cells are still poorly understood. It has been proposed that Ca(2+) homeostasis and Ca(2+) sensors, including calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII), play critical roles in spermatogenesis. Therefore, in the present study, we aimed to investigate whether a perturbation in Ca(2+)-CaM-CaMKII signaling was involved in the BPA-induced injury to mouse spermatocyte GC-2spd (ts) (GC-2) cells. Our results showed that BPA (range from 0.2 to 20 μM) induced obvious GC-2 cell injury, including decreased cell viability, the release of mitochondrial cytochrome c and the activation of caspase-3. However, these processes could be partially abrogated by pretreatment with a Ca(2+) chelator (BAPTA/AM), a CaM antagonist (W7) or a CaMKII inhibitor (KN93). These results, taken together, indicate that BPA exposure contributes to male germ cell injury, which may be partially mediated through a perturbation in Ca(2+)/CaM/CaMKII signaling and the mitochondrial apoptotic process.