Copper-Mediated Mitochondrial Fission/Fusion Is Associated with Intrinsic Apoptosis and Autophagy in the Testis Tissues of Chicken.

Abstract

The aim of this study is to investigate whether copper (Cu) could induce testicular poisoning and influence the mitochondrial dynamics, apoptosis, and autophagy in chickens. For this purpose, thirty-six 1-day-old male Hy-line chickens were divided into control group (C group) and test group (Cu group). The chickens were exposed to 0 (C group) or 300mg/kg (Cu group) of copper sulfate (CuSO4) for 30, 60, and 90days. CuSO4 was added into the basal diet to make supplements. Testis tissues were subjected to observation of ultrastructure and detection of testis-related indexes. The results indicated that in the test group, the levels of the pro-apoptotic genes were up-regulated and the levels of the anti-apoptotic genes were down-regulated; the levels of mitochondrial fission-related genes markedly increased, and the levels of mitochondrial fusion-related genes were highly decreased; autophagy-related gene (autophagy-associated gene 4B (ATG4B), dynein, microtubule-associated protein 1 light chain 3 beta (LC3-II), ATG5, and beclin-1) levels were increased, while mammalian target of rapamycin (mTOR) and LC3-I levels were declined. The results of transmission electron microscopy (TEM) demonstrated that Cu induced mitochondrial fragmentation, which induced autophagy and apoptosis in chicken testes. In conclusion, CuSO4 exposure can influence the mitochondrial dynamics balance and lead to mitochondria-initiated intrinsic pathway of apoptosis and autophagy, which triggers the testicular poisoning in chickens. What is more, there is a correlation among mitochondrial dynamics, apoptosis, and autophagy.