Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease

作者：Kuiyu Chen, Limin Wu, Qianzhuo Liu, Fang Tan, Luyao Wang, Dan Zhao, Xinru Fang, Xiang Liu, Jiabo Liu, Hui Han · 发表于：Biomedicine & Pharmacotherapy · 年份：2022 · DOI：10.1016/j.biopha.2022.114107 · 被引用次数：31 · 研究领域：Sperm and Testicular Function、Trace Elements in Health、Selenium in Biological Systems

BACKGROUND AND OBJECTIVE: There are considerable evidence of reproductive impairment in male organisms with Wilson disease (WD). The purpose of this study was to observe spermatogenesis, mitochondrial damage, apoptosis, and the level of oxidative stress in the testes of Wilson disease model TX mice, and to observe the effect and mechanism of glutathione on testicular spermatogenesis. METHODS: Mice were divided into a normal control group (control group), Wilson disease model TX mice group (WD group), penicillamine-treated TX mice group (penicillamine group) and glutathione-treated TX mice group (glutathione group). Testicular coefficient, histomorphology of testis and epididymis, number of spermatozoa, apoptosis of spermatogenic cells and expression of apoptosis-related proteins were observed. Ultrastructural analysis of mitochondria and mitochondrial membrane potential (MMP) monitored using JC-1 dye were used to detect mitochondrial damage. The levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and reactive oxygen species (ROS) in testicular cells were measured to assess oxidative stress. RESULTS: Testicular coefficient did not change in mice with Wilson disease. However, the tissue structure of the testicular seminiferous tubules was damaged, and the number of spermatozoa in the epididymal lumen was significantly reduced in WD group. The apoptosis rate in the testes was significantly increased. The protein expression of the pro-apoptotic proteins Bax and Ca...