Genome-wide DNA methylation analysis of oligospermia and asthenozoospermia in a Chinese population

Aberrant DNA methylation in sperm has been associated with infertility in male patients demonstrating low semen quality or defective spermatogenesis. The aim of this study was to analyze methylation levels of DNA in different types of disorders related to spermatogenesis, including oligospermia and asthenozoospermia. Illumina Infinium HD Human Methylation 450K arrays were used to identify genomic regions demonstrating variations in sperm DNA methylation patterns between 36 fertile and 36 infertile individuals. Based on genome-wide methylation chips, this study screened out a batch of differentially methylated genes related to the process of spermatogenesis. There were 776 genes showing significant methylation differences between the oligospermia group and fertile control group (Diff Score > 50, P < 0.001), while 2,142 genes with aberrant methylation were found in the asthenozoospermia group (Diff Score > 50, P < 0.001). About 189 genes showed differential methylation patterns in fertile individuals with a history of smoking or alcohol use (Diff Score > 30, P < 0.05). This study identified nine genes, predominantly expressed in the testis, and three genes that have not been commonly studied in relation to male infertility: PEG3, DYDC1, and MMEL1. Cluster analysis revealed that abnormally methylated genes in oligospermia were mainly associated with apoptosis and cell cycle proteins, while abnormally methylated genes in asthenozoospermia were mainly involved in ion channels, cytoskeleton, and flagellum motility. Thus, these genetic variations may lead to male infertility. Overall, present data suggests that aberrant sperm DNA methylation, along with certain risk factors, might contribute to different types of spermatogenic disorders. The current study provides a promising basis for future exploration of the molecular mechanisms underlying male infertility.