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Association between promoter methylation of MLH 1 and MSH 2 and reactive oxygen species in oligozoospermic men—A pilot study
Author(s) -
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.
Publication year - 2018
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.12903
Subject(s) - mlh1 , msh2 , methylation , dna methylation , biology , andrology , male infertility , genetics , dna mismatch repair , infertility , medicine , gene , dna repair , pregnancy , gene expression
Summary MLH 1 and MSH 2 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 MLH 1 and MSH 2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH 1 and MSH 2 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 MLH 1 and MSH 2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH 1 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 MLH 1 methylation. Contrary, no association between MSH 2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH 1 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 MLH 1 than normozoospermic patients. Whether hypermethylation of the MLH 1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation.