Alterations in sperm DNA methylation patterns of oligospermic males

Abstract

Aberrant in sperm DNA methylation patterns and histone modification play a role in male fecundity decline. This study was prepared to determine whether sperm DNA methylation at CpG dinucleotides is different in oligospermic males compared to proven fertile males and then to evaluate the correlation between the changes in sperm DNA methylation patterns and semen parameters of oligospermic males. A total of 165 males (64 proven fertile males "controls" and 101 oligospermic males "cases") were included in the study. Three CpG sites have the highest difference in methylation levels (cg23081194, cg25750688, and cg04807108) were underwent to further analysis using deep bisulfite sequencing in 125 samples (44 controls and 81 cases). The results of a validation study showed that variation in methylation levels was found in more than one CpG site: there was a significant alteration in methylation levels at all CpGs tested within the UBE2G2 and cg25750688 site related amplicon (p≤0.0001), and at eight CpGs (CpG1, CpG3, CpG6, CpG8, CpG11, CpG13, CpG14, and CpG15) within the cg04807108 site related amplicon (p≤0.0001) in cases compared to controls. Besides, a significant correlation was found between the changes in the methylation levels at different CpGs and semen parameters of case group. In conclusion, this study showed that these sites have a significant alteration in sperm DNA methylation levels in oligospermic males compared to proven fertile males, and these changes correlated with semen parameters.