Copper-Mediated Mitochondrial Fission/Fusion Is Associated with Intrinsic Apoptosis and Autophagy in the Testis Tissues of Chicken
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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 300 mg/kg (Cu group) of copper sulfate (CuSO4) for 30, 60, and 90 days. 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.
KeywordsCopper Chicken Testicular toxicity Apoptosis Autophagy Mitochondrial dynamics
This study was supported by the National Natural Science Foundation of China (Grant No. 31672619); the Fundamental Research Funds for the Central Universities (Grant No. 2572016EAJ5), and the National Key Research and Development Program of China (Grant No. 2017YFD0501702).
Compliance with Ethical Standards
The Animal Care, Use and Ethics Committee of Northeast Forestry University (approval no. UT-31; 20 June 2014) is responsible for review and approval of this animal experiment.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 11.Wang Y, Zhao H, Shao Y, Liu J, Li J, Xing M (2018) Interplay between elemental imbalance-related PI3K/Akt/mTOR-regulated apoptosis and autophagy in arsenic (III)-induced jejunum toxicity of chicken. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-018-2059-2
- 15.Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433–446CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Shahzad MN, Javed MT, Shabir S, Irfan M, Hussain R (2012) Effects of feeding urea and copper sulphate in different combinations on live body weight, carcass weight, percent weight to body weight of different organs and histopathological tissue changes in broilers. Exp Toxicol Pathol 64:141–147CrossRefPubMedGoogle Scholar
- 24.Pan T, Hu X, Liu T, Xu Z, Wan N, Zhang Y, Li S (2018) MiR-128-1-5p regulates tight junction induced by selenium deficiency via targeting CADM1 in broilers vein endothelial cells. J Cell Physiol. https://doi.org/10.1002/jcp.26794
- 34.Yu W, Zhao H, Shao Y, Liu J, Li J, Xing M (2017) Copper or/and arsenic induce oxidative stress-cascaded, nuclear factor kappa B-dependent inflammation and immune imbalance, trigging heat shock response in the kidney of chicken. Oncotarget 8:98103Google Scholar
- 45.Zhao C, Chen Z, Qi J, Duan S, Huang Z, Zhang C, Wu L, Zeng M, Zhang B, Wang N, Mao H, Zhang A, Xing C, Yuan Y (2017) Drp1-dependent mitophagy protects against cisplatin-induced apoptosis of renal tubular epithelial cells by improving mitochondrial function. Oncotarget 8:20988–21000PubMedPubMedCentralGoogle Scholar