Gunes S, Agarwal A, Henkel R, Mahmutoglu A M, Sharma R, Esteves S C, Aljowair A, Emirzeoglu D, Alkhani A, Pelegrini L, Joumah A, Sabanegh E
Medical Biology, Ondokuz Mayis University, Samsun, Turkey.
Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey.
Andrologia. 2018 Apr;50(3). doi: 10.1111/and.12903. Epub 2017 Oct 6.
MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation.
MLH1和MSH2是减数分裂期间DNA错配修复和交叉的重要基因，与男性不育有关。因此，研究了少精子症男性中DNA错配修复基因MLH1和MSH2的甲基化模式。分析了10例少精子症患者和29例正常精子捐献者。分析了MLH1和MSH2启动子的甲基化谱。此外，记录了精子活力和精液活性氧（ROS）。进行了受试者操作特征（ROC）分析，以确定MLH1和MSH2的DNA甲基化状态区分少精子症和正常精子症男性的准确性。与正常精子症男性相比，少精子症男性中MLH1的甲基化显著更高（p = 0.0013）。此外，精液ROS水平与MLH1甲基化之间存在显著正相关（r = 0.384；p = 0.0159）。相反，未发现MSH2甲基化与少精子症之间存在关联。MLH1甲基化状态的ROC曲线分析具有显著性（p = 0.0275），曲线下面积为61.1%，灵敏度为22.2%，特异性为100.0%。这项初步研究表明，少精子症患者的MLH1甲基化比正常精子症患者更多。MLH1启动子的高甲基化是否在特发性少精子症中精子DNA链的相关错配修复中起作用值得进一步研究。
