Promoter targeted bisulfite sequencing reveals DNA methylation profiles associated with low sperm motility in asthenozoospermia

Aberrant DNA methylation profiles have been associated with male infertility and some semen parameters. However, few studies systematically surveyed DNA methylation profiles associated with sperm motility in normozoospermia and asthenozoospermia. In this study, based on promoter targeted bisulfite sequencing technology, we provided a quantitative description on global DNA methylation profiles. The average global methylation values were 24.7% and the inter-individual variance was about 14.4%, while the intra-individual variance was about 3.9%. The difference between different motile sperm population or different participant groups was subtle and not significant. Furthermore, we identified 134 differentially methylated CpGs and 134 differentially variable CpGs in low motile sperm from asthenozoospermic patient (P < 0.05). Based on the literature, we further found 16 differentially methylated or variable genes which were required for spermatogenesis or sperm motility or dominantly expressed in testis. This study will provide potential markers for clinical diagnosis and a promising basis for understanding the effect of DNA methylation on asthenozoospermia. Overall design: This is case-control study investigating DNA methylation of CpGs in functionally important regions of high and low motile sperm population from normozoospermic controls (n=8) and asthenozoospermic cases (n=7).