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Author Spotlight: A Live Cell Imaging Technique to Study Calcium Signaling and Acrosome Exocytosis in Mouse Sperm
Published on: October 13, 2023
Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway
Hao Liu1, Rong Wang1, Huijuan OuYang1
1Department 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.
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.
Insights
Cadmium chloride induces spermatogonial cell apoptosis by increasing reactive oxygen species and activating the IP3R-MCU pathway, leading to mitochondrial calcium overload. This mechanism highlights cadmium
Area of Science:
- Reproductive Toxicology
- Cell Biology
- Environmental Health
Background:
- Cadmium (Cd) is a toxic metal and a known reproductive toxicant.
- The precise mechanism by which Cd induces germ cell apoptosis in testes is not fully understood.
Purpose of the Study:
- To investigate the in vitro cytotoxicity of cadmium chloride (CdCl2) on GC-1 spermatogonial cells.
- To elucidate the molecular mechanisms underlying CdCl2-induced apoptosis in spermatogonia.
Main Methods:
- Exposure of GC-1 spermatogonial cells to CdCl2.
- Measurement of reactive oxygen species (ROS) levels.
- Assessment of mitochondrial dysfunction, including AIF and Cyt-c release.
- Analysis of the IP3R-MCU pathway and calcium (Ca2+) transfer.
- Evaluation of apoptosis rates and BAPTA-AM intervention.
Main Results:
- CdCl2 increased ROS levels and induced apoptosis in spermatogonial cells.
- CdCl2 activated the IP3R-MCU pathway, causing endoplasmic reticulum to mitochondria Ca2+ transfer and mitochondrial Ca2+ overload.
- BAPTA-AM (calcium chelator) reversed CdCl2-induced IP3R phosphorylation, VDAC1, MCU, MCUR1 expression changes, ROS production, mitochondrial release of AIF and Cyt-c, and apoptosis.
Conclusions:
- CdCl2 induces spermatogonial apoptosis through mitochondrial Ca2+ overload.
- The IP3R-MCU signaling pathway mediates CdCl2-induced reproductive toxicity.
- Targeting the IP3R-MCU pathway may offer a strategy to mitigate cadmium's reproductive effects.
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