Epimedium protects against dyszoospermia in mice with Pex3 knockout by exerting antioxidant effects and regulating the expression level of P16.
Epimedium protects against dyszoospermia in mice with Pex3 knockout by exerting antioxidant effects and regulating the expression level of P16.
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淫羊藿通过发挥抗氧化作用和调节 P16 的表达水平来预防 Pex3 敲除小鼠的精子障碍
DOI：
10.1038/s41419-021-04435-8
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发表时间：
2022-01-20
影响因子：
9
通讯作者：
Qian Y
中科院分区：
文献类型：
--
作者：
Zhao H;Zhao T;Yang J;Huang Q;Wu H;Pan Y;Wang H;Qian Y
氧化应激（OS）是导致男性不育的首要因素之一。迄今为止，已发现口服抗氧化剂可以显着提高人类精子的质量。因此，抗氧化治疗已成为国际男性不育专家的共识。本研究以过氧化物酶体生物发生因子3（Pex3）敲除（KO，−/−）小鼠为模型，比较三种中药颗粒（淫羊藿[YYH]、菟丝子[TSZ]和红景天[HJT]）对男性生殖功能挽救的功效。 YYH被证明是最好的，并且对患有精子发生缺陷的Pex3−/−小鼠发挥了拯救作用。此外，YYH显着降低Pex3−/−雄性小鼠睾丸中ROS水平，抑制生精细胞DNA氧化损伤，促进生精细胞增殖，抑制细胞凋亡。此外，通过建立细胞周期蛋白依赖性激酶抑制剂 2 A (P16Ink4a)-KO 小鼠，证实了 YYH 改善精子障碍的机制。具体来说，Pex3−/− 小鼠产生大量的 ROS，这会损害生殖细胞 DNA，并进一步激活细胞衰老调节蛋白 P16-CDK6 的信号通路，导致细胞周期停滞，最终导致精子发生功能障碍。 YYH补充通过影响P16表达水平部分纠正了基因KO小鼠的相关表型，从而在一定程度上改善了生殖结果。
Oxidative stress (OS) is one of the primary factors leading to male infertility. Oral administration of antioxidants has thus far been found to significantly improve the quality of human sperm. Therefore, antioxidant treatment has become the consensus among international experts on male infertility. In this study, peroxisomal biogenesis factor 3 (Pex3)-knockout (KO, −/−) mice were used as a model to compare the efficacy of three types of traditional Chinese medicine (TCM) granules (Epimedium [YYH], Cuscuta [TSZ], and Rhodiola [HJT]) for male reproductive function rescue. YYH was revealed to be the best and exerted a rescue effect on Pex3−/− mice with spermatogenesis defects. In addition, YYH prominently reduced ROS levels in the testes, inhibited DNA oxidative damage in spermatogenic cells, promoted the proliferation of spermatogenic cells, and inhibited apoptosis in Pex3−/− male mice. Furthermore, the mechanism by which YYH ameliorated dyszoospermia was confirmed via the establishment of cyclin-dependent kinase inhibitor 2 A (P16Ink4a)-KO mice. Specifically, Pex3−/− mice produced elevated amounts of ROS, which damaged germ cell DNA and further activated the signaling pathway of the cell senescence regulatory protein P16-CDK6, resulting in cell cycle arrest and eventually contributing to spermatogenesis dysfunction. YYH supplementation partially corrected the associated phenotype in gene KO mice by affecting P16 expression levels, thus improving the reproductive outcome to a certain extent.
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影响因子：
--
作者：
Li Y;Pham V;Bui M;Song L;Wu C;Walia A;Uchio E;Smith-Liu F;Zi X
通讯作者：
Zi X
影响因子：
5.6
作者：
Sayed SMA;Siems K;Schmitz-Linneweber C;Luyten W;Saul N
通讯作者：
Saul N
影响因子：
7.7
作者：
Li, Dianrong;Meng, Lingjun;Wang, Xiaodong
通讯作者：
Wang, Xiaodong
影响因子：
2
作者：
Jiang, Huan;Zhu, Wei-Jie;Gu, Yi-Qun
通讯作者：
Gu, Yi-Qun
影响因子：
9.8
作者：
Betteridge, DJ
通讯作者：
Betteridge, DJ