Autophagy in Sertoli cell protects against environmental cadmium-induced germ cell apoptosis in mouse testes.

Guo-Xiang Zhou, Hua-Long Zhu, Xue-Ting Shi, Yuan Nan, Wei-Bo Liu, Li-Min Dai, Yong-Wei Xiong, Song-Jia Yi, Xue-Lin Cao, De-Xiang Xu, Hua Wang

Environmental pollution (Barking, Essex : 1987) 2021 Feb 01

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Cadmium (Cd) was an environmental pollutant, which could result in germ cell apoptosis in testes. Sertoli-germ cell communication was vital for germ cell development and maturity. However, little was known about the effect of Sertoli cell autophagy on Cd-induced germ cell apoptosis. Here, we used male Amh-Cre+/Atg5flox/flox (Atg5-/-) mice, loss of autophagy-related gene 5 (Atg5) in testicular Sertoli cells, to explore the obscure effects. Atg5-/- and Wild-type (WT) mice were given with cadmium chloride (CdCl2, 2.0 mg/kg) for 0-24 h. Our results showed that Cd triggered testicular germ cell apoptosis, as evidenced by the increment of TUNEL-labeled germ cells, cleaved caspase3 and cleaved poly (ADP-ribose) polymerase protein level. Additionally, Cd induced testicular autophagy, as determined by elevating the level of autophagy-related proteins, including Atg5, Atg7, LC3B-II, and the gathering of LC3 puncta. 3-methyladenine, a specific autophagy inhibitor, exacerbated Cd-caused germ cell apoptosis. Inversely, rapamycin, an autophagy inducer, relieved Cd-stimulated germ cell apoptosis. Interestingly, we found that autophagy in Sertoli cells was activated in Cd-treated WT mouse testes as evidenced by the increment of LC3 puncta surrounding SOX9, a specific Sertoli cell marker. More importantly, loss of autophagy in Sertoli cells aggravated Cd-triggered germ cell apoptosis. Taken together, these data indicate that autophagy in Sertoli cells alleviates Cd-triggered germ cell apoptosis in mouse testes. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Guo-Xiang Zhou, Hua-Long Zhu, Xue-Ting Shi, Yuan Nan, Wei-Bo Liu, Li-Min Dai, Yong-Wei Xiong, Song-Jia Yi, Xue-Lin Cao, De-Xiang Xu, Hua Wang. Autophagy in Sertoli cell protects against environmental cadmium-induced germ cell apoptosis in mouse testes. Environmental pollution (Barking, Essex : 1987). 2021 Feb 01;270:116241