• PMID: 28983945
• Gene Name: MLH1
• Condition: Oligozoospermia, Male infertility
• Association: Associated
• Population size: 39
• Population details: 39 (10 oligozoospermia, 29 normozoospermia patients)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Oligozoospermia, Male infertility

Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study

Gunes S, Agarwal A, Henkel R, Mahmutoglu AM, Sharma R, Esteves SC, Aljowair A, Emirzeoglu D, Alkhani A, Pelegrini L, Joumah A, Sabanegh E.

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. CI - © 2017 Blackwell Verlag GmbH. FAU - Gunes, S AU - Gunes S AD - Medical Biology, Ondokuz Mayis University, Samsun, Turkey. AD - Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey. FAU - Agarwal, A AU - Agarwal A AUID- ORCID: 0000-0003-0585-1026 AD - Cleveland Clinic, American Center for Reproductive Medicine, Cleveland, OH, USA. FAU - Henkel, R AU - Henkel R AUID- ORCID: 0000-0003-1128-2982 AD - Department of Medical Bioscience, University of Western Cape, Bellville, South Africa. FAU - Mahmutoglu, A M AU - Mahmutoglu AM AD - Medical Biology, Ondokuz Mayis University, Samsun, Turkey. FAU - Sharma, R AU - Sharma R AUID- ORCID: 0000-0002-9664-6978 AD - Cleveland Clinic, American Center for Reproductive Medicine, Cleveland, OH, USA. FAU - Esteves, S C AU - Esteves SC AUID- ORCID: 0000-0002-1313-9680 AD - ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, Brazil. FAU - Aljowair, A AU - Aljowair A AD - Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia. FAU - Emirzeoglu, D AU - Emirzeoglu D AD - Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey. FAU - Alkhani, A AU - Alkhani A AD - Alfaisal University, Riyadh, Saudi Arabia. FAU - Pelegrini, L AU - Pelegrini L AD - University of Sao Paulo, Sao Paulo, Brazil. FAU - Joumah, A AU - Joumah A AD - Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.