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

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+/Atg5^flox/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 (CdCl_2, 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.

Apoptosis; Autophagy; Cadmium; Sertoli cell; Testes.