State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
FASEB J. 2019 Jun;33(6):7427-7436. doi: 10.1096/fj.201801962RR. Epub 2019 Apr 18.
X-ray repair cross-complementing group 1 (), a key DNA repair gene, plays a vital role in maintaining genomic stability and is highly expressed in the early stages of spermatogenesis, but the exact functions remain elusive. Here we generated primordial germ cell-specific knockout (c) mice to elucidate the effects of on spermatogenesis. We demonstrated that deficiency results in infertility in male mice due to impaired spermatogenesis. We found that c mice exhibited smaller size of testes as well as lower sperm concentration and motility than the wild-type mice. Mechanistically, we demonstrated that deficiency in primordial germ cells induced elevated levels of reactive oxygen species, mitochondria dysfunction, apoptosis, and loss of stemness of spermatogonial stem cells (SSCs) in testes. In -deficienct SSCs, elevated oxidative stress and mitochondrial dysfunction could be partially reversed by treatment with the antioxidant -acetylcysteine (NAC), whereas NAC treatment did not restore the fertility or ameliorate the apoptosis caused by loss of . Overall, our findings provided new insights into understanding the crucial role of during spermatogenesis.-Xu, C., Xu, J., Ji, G., Liu, Q., Shao, W., Chen, Y., Gu, J., Weng, Z., Zhang, X., Wang, Y., Gu, A. Deficiency of X-ray repair cross-complementing group 1 in primordial germ cells contributes to male infertility.
X 射线修复交叉互补基因 1 (), 一个关键的 DNA 修复基因, 在维持基因组稳定性方面发挥着重要作用, 在精子发生的早期高度表达, 但确切的功能仍不清楚。在这里, 我们生成了原始生殖细胞特异性 敲除 (c) 小鼠, 以阐明 对精子发生的影响。我们证明 缺乏导致雄性小鼠不育, 因为精子发生受损。我们发现 c 小鼠的睾丸体积较小, 精子浓度和活力低于野生型小鼠。从机制上讲, 我们证明原始生殖细胞中的 缺乏导致睾丸中活性氧水平升高、线粒体功能障碍、凋亡和精原干细胞 (SSCs) 干性丧失。在 -缺陷 SSCs 中, 抗氧化剂 -乙酰半胱氨酸 (NAC) 的处理部分逆转了氧化应激和线粒体功能障碍的升高, 而 NAC 处理不能恢复由 缺失引起的生育能力或改善凋亡。总的来说, 我们的研究结果为理解 在精子发生过程中的关键作用提供了新的见解。-徐, C., 徐, J., 纪, G., 刘, Q., 邵, W., 陈, Y., 顾, J., 翁, Z., 张, X., 王, Y., 顾, A. 原始生殖细胞中 X 射线修复交叉互补基因 1 的缺乏导致男性不育。