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The toxic effects of Bisphenol A on the mouse spermatocyte GC‐2 cell line: the role of the Ca 2+ ‐calmodulin‐Ca 2+ /calmodulin‐dependent protein kinase II axis
Author(s) -
Qian Wenyi,
Wang Yixin,
Zhu Jingying,
Mao Changfei,
Wang Qiang,
Huan Fei,
Cheng Jie,
Liu Yanqing,
Wang Jun,
Xiao Hang
Publication year - 2015
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3188
Subject(s) - calmodulin , spermatocyte , viability assay , chemistry , protein kinase a , microbiology and biotechnology , kinase , biology , apoptosis , biochemistry , enzyme , meiosis , gene
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. Copyright © 2015 John Wiley & Sons, Ltd.