精子DNA损伤的机制和临床相关性

Mechanisms and Clinical Relevance of Sperm DNA Damage

精子发生是维持和促进男性生育能力的重要过程,涉及多种细胞类型、调控分子、修复机制和表观遗传调控因子。在生精后期,由于精子DNA修复系统功能失调和活性氧的过量产生,对细胞核和线粒体DNA造成损伤,引起精子发生与凋亡异常,降低自然妊娠的概率。精子DNA损伤的机制主要包括复制错误和精子DNA片段化(sperm DNA fragmentation,SDF)。SDF可能与男性不育、辅助生殖结局以及后代的生长发育有关。临床上通过检测SDF水平评估DNA损伤程度。研究精子DNA损伤的发生及其潜在机制有助于临床上改善不孕症患者的临床治疗结局。综述精子发生、精原细胞调节和精子分化的过程,并介绍DNA损伤机制的研究现状及其对辅助生殖结局的影响。

Spermatogenesis is an important process for maintaining and promoting male fertility,involving a variety of cell types,regulatory molecules,repair mechanisms and epigenetic regulators.In the later stage of spermatogenesis,the dysfunction of the sperm DNA repair system and the excessive production of reactive oxygen species may damage the nucleus and mitochondrial DNA,causing abnormal spermatogenesis and apoptosis and reducing the probability of natural conception.The sources of sperm DNA damage mainly include replication errors and sperm DNA fragmentation(SDF),which may be related to male infertility,assisted reproduction outcomes,and the growth and development of offspring.The sperm DNA damage can be evaluated by measuring SDF level.Studying the occurrence and mechanisms of sperm DNA damage can help to improve the clinical outcomes in infertile patients.This article reviews the processes of spermatogenesis,spermatogonia regulation and sperm differentiation,and introduces the DNA damage and its impact on the assisted reproduction outcomes.