Deficiency of X-ray repair cross-complementing group 1 in primordial germ cells contributes to male infertility
Deficiency of X-ray repair cross-complementing group 1 in primordial germ cells contributes to male infertility
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原始生殖细胞中 X 射线修复交叉互补组 1 的缺陷导致男性不育
DOI：
10.1096/fj.201801962rr
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Gu Aihua
中科院分区：
文献类型：
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作者：
Xu Cheng;Xu Jin;Ji Guixiang;Liu Qian;Shao Wentao;Chen Yaoyao;Gu Jie;Weng Zhenkun;Zhang Xin;Wang Yubang;Gu Aihua
X射线修复交叉互补组1 （Xrcc1）是一种关键的DNA修复基因，在维持基因组稳定性中起着至关重要的作用，在精子发生的早期阶段高度表达，但其确切功能尚不清楚。在这里，我们产生了原始生殖细胞特异性xrcc1敲除（cXrcc1−/−）小鼠来阐明xrcc1对精子发生的影响。我们证明xrcc1缺乏导致雄性小鼠由于精子发生受损而不育。我们发现，与野生型小鼠相比，cXrcc1 - / -小鼠表现出更小的睾丸尺寸，以及更低的精子浓度和活力。从机制上讲，我们证明了原始生殖细胞中xrcc1的缺乏会导致睾丸中活性氧水平升高、线粒体功能障碍、细胞凋亡和精原干细胞（SSCs）的干性丧失。使用抗氧化剂n -乙酰半胱氨酸（NAC）治疗xrcc1缺失的ssc，可以部分逆转氧化应激升高和线粒体功能障碍，而NAC治疗不能恢复生育能力或改善xrcc1缺失引起的细胞凋亡。总之，我们的发现为理解xrcc1在精子发生过程中的关键作用提供了新的见解。-徐超，徐军，纪刚，刘强，邵伟，陈毅，顾军，翁志强，张晓霞，王勇，顾安。原始生殖细胞X射线修复交叉互补组1缺乏与男性不育的关系。中国生物医学工程学报，32(1),444 - 444（2019）。www.fasebj.org
X‐ray repair cross‐complementing group 1 (Xrcc1), 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–specificXrcc1knockout (cXrcc1−/−) mice to elucidate the effects ofXrcc1on spermatogenesis. We demonstrated thatXrcc1deficiency results in infertility in male mice due to impaired spermatogenesis. We found that cXrcc1−/−mice exhibited smaller size of testes as well as lower sperm concentration and motility than the wild‐type mice. Mechanistically, we demonstrated thatXrcc1deficiency 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. InXrcc1‐deficienct SSCs, elevated oxidative stress and mitochondrial dysfunction could be partially reversed by treatment with the antioxidantN‐acetylcysteine (NAC), whereas NAC treatment did not restore the fertility or ameliorate the apoptosis caused by loss ofXrcc1. Overall, our findings provided new insights into understanding the crucial role ofXrcc1during 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. FASEB J. 33, 7427–7436 (2019). www.fasebj.org