Metin Mahmutoglu Asli, Gunes Sezgin, Asci Ramazan, Henkel Ralf, Aydin Oguz
Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey.
Department of Multidisciplinary Molecular Medicine, Graduate School of Health Sciences, Ondokuz Mayis University, Samsun, Turkey.
Andrologia. 2021 Mar;53(2):e13925. doi: 10.1111/and.13925. Epub 2020 Dec 23.
The aim of the study was to investigate whether the promoter methylation of XRCC1 and ERCC2 genes is associated with sperm DNA fragmentation and chromatin condensation in idiopathic oligoasthenoteratozoospermic men. This study involved 77 infertile men with idiopathic oligoasthenoteratozoospermia and 51 normozoospermic controls. The methylight method, TUNEL assay and aniline blue staining were used for the evaluation of XRCC1 and ERCC2 genes' methylation, SDF and sperm chromatin condensation, respectively. SDF (p = .004) and XRCC1 methylation (p = .0056) were found to be significantly higher in men with idiopathic OAT than in the controls, while mature spermatozoa frequency was higher in controls as compared to infertile men (p < .0001). No significant association was found between SDF and methylation of XRCC1 and ERCC2 genes (p = .9277 and p = .8257, respectively). However, compared to the cut-off point obtained by receiver operating characteristic analysis, a significant association was found between SDF and XRCC1 methylation, positive and negative methylation groups, generated according to the cut-off value for XRCC1. XRCC1 methylation was found to have a significant effect on chromatin condensation (p = .0017). No significant difference was detected among ERCC2 methylation, male infertility and SDF. In conclusion, XRCC1 methylation may have a role in sperm chromatin condensation and idiopathic OAT.
本研究旨在调查X射线修复交叉互补蛋白1(XRCC1)和切除修复交叉互补蛋白2(ERCC2)基因的启动子甲基化是否与特发性少弱畸精子症男性的精子DNA片段化及染色质凝聚有关。本研究纳入了77例特发性少弱畸精子症不育男性和51例正常精子症对照。分别采用甲基化特异性荧光定量聚合酶链反应(Methylight)法、脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法和苯胺蓝染色来评估XRCC1和ERCC2基因的甲基化、精子DNA碎片率(SDF)和精子染色质凝聚情况。结果发现,特发性少弱畸精子症男性的SDF(p = 0.004)和XRCC1甲基化(p = 0.0056)显著高于对照组,而对照组的成熟精子频率高于不育男性(p < 0.0001)。未发现SDF与XRCC1和ERCC2基因甲基化之间存在显著关联(分别为p = 0.9277和p = 0.8257)。然而,与通过受试者工作特征分析获得的截断点相比,发现SDF与XRCC1甲基化之间存在显著关联,根据XRCC1的截断值产生了阳性和阴性甲基化组。发现XRCC1甲基化对染色质凝聚有显著影响(p = 0.0017)。未检测到ERCC2甲基化、男性不育和SDF之间存在显著差异。总之,XRCC1甲基化可能在精子染色质凝聚和特发性少弱畸精子症中起作用。