Wang Jing-Jing, Wang Shu-Xia, Feng Yan, Zhang Rui-Fen, Li Xin-Yue, Sun Qiong, Ding Jian
School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Pharmaceuticals (Basel). 2022 Apr 23;15(5):519. doi: 10.3390/ph15050519.
Mitochondria are structurally and functionally unique organelles in male gametes. Apparently, as the only organelles remaining in mature sperm, mitochondria not only produce adeno-sine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to support sperm mobility, but also play key roles in regulating reactive oxidation species (ROS) signaling, calcium homeostasis, steroid hormone biosynthesis, and apoptosis. Mitochondrial dysfunction is often associated with the aging process. Age-dependent alterations of the epididymis can cause alterations in sperm mitochondrial functioning. The resultant cellular defects in sperm have been implicated in male infertility. Among these, oxidative stress (OS) due to the overproduction of ROS in mitochondria may represent one of the major causes of these disorders. Excessive ROS can trigger DNA damage, disturb calcium homeostasis, impair OXPHOS, disrupt the integrity of the sperm lipid membrane, and induce apoptosis. Given these facts, scavenging ROS by antioxidants hold great potential in terms of finding promising therapeutic strategies to treat male infertility. Here, we summarize the progress made in understanding mitochondrial dysfunction, aging, and male infertility. The clinical potential of antioxidant interventions was also discussed.
线粒体是雄配子中结构和功能独特的细胞器。显然，作为成熟精子中仅存的细胞器，线粒体不仅通过氧化磷酸化（OXPHOS）产生三磷酸腺苷（ATP）以支持精子运动，还在调节活性氧化物质（ROS）信号传导、钙稳态、类固醇激素生物合成和细胞凋亡中发挥关键作用。线粒体功能障碍常与衰老过程相关。附睾的年龄依赖性改变可导致精子线粒体功能的改变。精子中由此产生的细胞缺陷与男性不育有关。其中，线粒体中ROS过量产生导致的氧化应激（OS）可能是这些疾病的主要原因之一。过量的ROS可引发DNA损伤、扰乱钙稳态、损害氧化磷酸化、破坏精子脂质膜的完整性并诱导细胞凋亡。鉴于这些事实，通过抗氧化剂清除ROS在寻找治疗男性不育的有前景的治疗策略方面具有巨大潜力。在此，我们总结了在理解线粒体功能障碍、衰老和男性不育方面取得的进展。还讨论了抗氧化剂干预的临床潜力。
