Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic menA pilot study
Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic menA pilot study
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DOI：
10.1111/and.12903
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发表时间：
2018-04-01
期刊：
影响因子：
2.4
通讯作者：
Sabanegh, E.
中科院分区：
文献类型：
--
作者：
Gunes, S.;Agarwal, A.;Sabanegh, E.
MLH1和MSH2是减数分裂过程中DNA错配修复和杂交的重要基因，与男性不育有关。因此，我们研究了DNA错配修复基因MLH1和MSH2在少精子雄性中的甲基化模式。对10例少精子患者和29例正常精子供者进行了分析。分析了MLH1和MSH2启动子的甲基化谱。此外，还记录了精子活力和精子活性氧（ROS）。进行受试者工作特征（ROC）分析，以确定MLH1和MSH2 DNA甲基化状态的准确性，以区分少精子和正常精子男性。在少精子男性中，MLH1的甲基化程度明显高于正常精子男性（p= 0.0013）。此外，精子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，没有发现MSH2甲基化与少精症之间的关联。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%，敏感性为22.2%，特异性为100.0%。这项初步研究表明，少精子患者比正常精子患者有更多的MLH1甲基化。在特发性少精症中，MLH1启动子的高甲基化是否在修复精子DNA链相关错配中发挥作用，值得进一步研究。
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.