Li Nihong, Wang Hong, Zou Siying, Yu Xujun, Li Junjun
Chengdu Fifth People's Hospital, The Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China.
College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Reprod Sci. 2025 Jan;32(1):41-51. doi: 10.1007/s43032-024-01714-5. Epub 2024 Sep 27.
DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.
精子中的DNA损伤是男性不育的主要原因。它还与不良生殖结果相关（包括受精率降低、胚胎质量和妊娠率下降以及自然流产率升高）。精子DNA的损伤发生在精子的产生和成熟过程中，以及它们通过男性生殖道的过程中。DNA损伤修复通常发生在精子发生、受精后的卵母细胞以及早期胚胎发育阶段。已知的精子DNA修复机制主要包括核苷酸切除修复（NER）、碱基切除修复（BER）、错配修复（MMR）和双链断裂修复（DSBR）。精子DNA损伤最严重的类型是双链断裂，它将通过DSBR进行修复，包括同源重组（HR）、经典非同源末端连接（cNHEJ）、替代末端连接（aEJ）和单链退火（SSA）。然而，精子中DNA修复的精确机制仍未完全了解。DNA修复相关蛋白在精子DNA修复中具有重要价值。几种与修复相关的蛋白已被确定在浓缩染色质、调节转录、修复DNA损伤和调节细胞周期中发挥关键作用。值得注意的是，XRCC4样因子（XLF）和XRCC4与XLF的旁系同源物（PAXX）介导的二聚化促进了cNHEJ修复中填充末端的加工，这表明XLF和PAXX在精子DNA修复机制中具有潜在价值。本综述总结了精子DNA损伤的经典和潜在修复机制，旨在为进一步研究DNA损伤修复机制提供一个视角。
