Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway. (1st March 2023)

• Record Type: Journal Article
• Authors: Liu, Hao; Wang, Rong; OuYang, Huijuan; Wang, Yi; Wu, Jie; Li, Mengyuan; Hu, Yuan; Yao, Yuyou; Liu, Yehao; Ji, Yanli
• Is Part Of: Toxicology. Volume 486(2023)
• Publication Date: 2023-03-01
• Subjects: Environmental cadmium -- Apoptosis -- Spermatogonia -- Mitochondrial Ca2+ overload -- IP3R -- MCU; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2023.153448
• Languages: English
• ISSNs: 0300-483X

Abstract

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 IP3 R-MCU pathway, trigger Ca 2+ transfer from endoplasmic reticulum to mitochondria, and cause mitochondrial Ca 2+ overload. BAPTA acetoxymethyl ester (BAPTA-AM), a calcium chelator, almost completely attenuated IP3 R 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 Ca 2+ overload mediated by IP3 R-MCU signal pathway. Highlights: Cd induced spermatogonia apoptosis. Cd caused mitochondrial Ca 2+ overload. Cd activated IP3 R-MCU calcium regulation axis.