Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease
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,...
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| Language: | English |
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Elsevier
2023-02-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222014962 |
| _version_ | 1811177263241101312 |
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| author | Kuiyu Chen Limin Wu Qianzhuo Liu Fang Tan Luyao Wang Dan Zhao Xinru Fang Xiang Liu Jiabo Liu Hui Han |
| author_facet | Kuiyu Chen Limin Wu Qianzhuo Liu Fang Tan Luyao Wang Dan Zhao Xinru Fang Xiang Liu Jiabo Liu Hui Han |
| author_sort | Kuiyu Chen |
| collection | DOAJ |
| description | 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 Caspase-3 significantly increased, and the expressions of the anti-apoptotic protein Bcl-2 significantly decreased. The levels of ROS and MDA significantly increased, and the levels of CAT and GSH significantly decreased. Mitochondria with abnormal ultrastructure and the rate of JC-1 positive cells were significantly increased in the WD group. After copper chelation by penicillamine, the structure of the testicular seminiferous tubules and the number of spermatozoa in the epididymal lumen were significantly improved. The number of apoptotic cells was significantly reduced. The levels of Bax and Caspase-3 decreased, and the expression of Bcl-2 increased. The contents of CAT and GSH increased, and the levels of ROS and MDA decreased significantly. The abnormal mitochondria and JC-1 positive cells was significantly decreased. The histomorphology of seminiferous tubules, spermatogenic function, apoptosis rate, apoptosis-related proteins, mitochondrial damage, and oxidative stress in Wilson disease TX mice significantly improved after glutathione treatment. Conclusion: Copper deposition in Wilson disease can lead to oxidative stress injury, mitochondrial damage, and apoptosis in the testis, leading to the impairment of spermatogenesis. Glutathione may improve testicular spermatogenesis in male Wilson disease TX mice by inhibiting copper deposition-induced oxidative stress, mitochondrial damage, and apoptosis. |
| first_indexed | 2024-04-10T22:58:45Z |
| format | Article |
| id | doaj.art-2276eac9064a4aebb91a898b455f128e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T22:58:45Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-2276eac9064a4aebb91a898b455f128e2023-01-14T04:25:48ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-02-01158114107Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson diseaseKuiyu Chen0Limin Wu1Qianzhuo Liu2Fang Tan3Luyao Wang4Dan Zhao5Xinru Fang6Xiang Liu7Jiabo Liu8Hui Han9Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaReproductive and genetic branch, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Corresponding authors.Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China; Corresponding authors.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 Caspase-3 significantly increased, and the expressions of the anti-apoptotic protein Bcl-2 significantly decreased. The levels of ROS and MDA significantly increased, and the levels of CAT and GSH significantly decreased. Mitochondria with abnormal ultrastructure and the rate of JC-1 positive cells were significantly increased in the WD group. After copper chelation by penicillamine, the structure of the testicular seminiferous tubules and the number of spermatozoa in the epididymal lumen were significantly improved. The number of apoptotic cells was significantly reduced. The levels of Bax and Caspase-3 decreased, and the expression of Bcl-2 increased. The contents of CAT and GSH increased, and the levels of ROS and MDA decreased significantly. The abnormal mitochondria and JC-1 positive cells was significantly decreased. The histomorphology of seminiferous tubules, spermatogenic function, apoptosis rate, apoptosis-related proteins, mitochondrial damage, and oxidative stress in Wilson disease TX mice significantly improved after glutathione treatment. Conclusion: Copper deposition in Wilson disease can lead to oxidative stress injury, mitochondrial damage, and apoptosis in the testis, leading to the impairment of spermatogenesis. Glutathione may improve testicular spermatogenesis in male Wilson disease TX mice by inhibiting copper deposition-induced oxidative stress, mitochondrial damage, and apoptosis.http://www.sciencedirect.com/science/article/pii/S0753332222014962Wilson diseaseGlutathioneCopper depositionOxidative stressMitochondrial damageApoptosis |
| spellingShingle | Kuiyu Chen Limin Wu Qianzhuo Liu Fang Tan Luyao Wang Dan Zhao Xinru Fang Xiang Liu Jiabo Liu Hui Han Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease Biomedicine & Pharmacotherapy Wilson disease Glutathione Copper deposition Oxidative stress Mitochondrial damage Apoptosis |
| title | Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease |
| title_full | Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease |
| title_fullStr | Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease |
| title_full_unstemmed | Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease |
| title_short | Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease |
| title_sort | glutathione improves testicular spermatogenesis through inhibiting oxidative stress mitochondrial damage and apoptosis induced by copper deposition in mice with wilson disease |
| topic | Wilson disease Glutathione Copper deposition Oxidative stress Mitochondrial damage Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222014962 |
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