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  3. Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway

Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway

  • Toxicology. 2023 Jan 31;486:153448. doi: 10.1016/j.tox.2023.153448.
Hao Liu 1,  Rong Wang 1,  Huijuan OuYang 1,  Yi Wang 2,  Jie Wu 2,  Mengyuan Li 2,  Yuan Hu 2,  Yuyou Yao 3,  Yehao Liu 4,  Yanli Ji 5
Affiliations

Affiliations

  • 1 Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, Anhui, China.
  • 2 Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China.
  • 3 Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, 230032 Anhui, China.
  • 4 Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, 230032 Anhui, China. Electronic address: liuyehao@ahmu.edu.cn.
  • 5 Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, 230032 Anhui, China. Electronic address: ylji@ahmu.edu.cn.
PMID: 36731763 DOI: 10.1016/j.tox.2023.153448
Abstract

Cadmium (Cd) is a toxic metal and also a well-known reproductive toxicant. Cd could induce germ cells Apoptosis in mouse testes, however, the mechanism remains unclear. This study designed in vitro using GC-1 spermatogonial (spg) cells to explore the cytotoxicity and the molecular mechanisms induced by cadmium chloride(CdCl2). As expected, CdCl2 elevated the levels of Reactive Oxygen Species (ROS) and induced the release of AIF and Cyt-c from the mitochondria to the cytosol in spermatogonia. Correspondingly, CdCl2 apparently increased the apoptotic rate in spermatogonia. Further researches found that CdCl2 could activate IP3R-MCU pathway, trigger CA2+ transfer from endoplasmic reticulum to mitochondria, and cause mitochondrial CA2+ overload. BAPTA acetoxymethyl ester (BAPTA-AM), a calcium chelator, almost completely attenuated IP3R phosphorylation, inhibited the mRNA and protein expression levels of VDAC1, MCU and MCUR1 upregulated by CdCl2, reduced the calcium ion content in the mitochondria. Moreover, BAPTA-AM could decrease the level of ROS, antagonize CdCl2-induced release of AIF and Cyt-c from the mitochondria to the cytosol and alleviate CdCl2-induced Apoptosis in spermatogonia. As above, these results provided the evidence that CdCl2 might induce Apoptosis of spermatogonia via mitochondrial CA2+ overload mediated by IP3R-MCU signal pathway.

Keywords

Apoptosis; Environmental cadmium; IP(3)R; MCU; Mitochondrial Ca(2+) overload; Spermatogonia.

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