DNA methylation levels of imprinted and nonimprinted genes DMRs associated with defective human spermatozoa.

Abstract

Asthenozoospermia (AS) is a common cause of human male infertility. Recent studies have shown significant associations of aberrant DNA methylation in spermatozoa with male infertility. The aims of the this investigation were to assess the changes in DNA methylation of known imprinted genes (MEST, GNAS and H19), novel imprinted gene (FAM50B) and nonimprinted genes (LINE-1 and P16) DMRs in the spermatozoa of infertile men with single-factor AS. Semen samples were obtained from 46 AS patients and 49 age-matched normal controls. DNA methylation levels of detected genes DMR were determined by MassARRAY quantitative methylation analysis. The average methylation level at the P16 and MEST DMRs was significantly lower in AS patients than in controls (patients 6.51±0.32%, controls 7.66±0.40%, P<0.01). The methylation level of 6 CpG sites of P16 DMR, and 1 CpG site of MEST, GNAS, FAM50B and LINE-1 DMRs, was lower in AS group than in control group. For the first time, the data presented here suggest that increased methylation defects of P16 DMR may be associated with low sperm motility. This study provides the potential association between low sperm motility infertile men and the aberrant DNA methylation of MEST, LINE-1, GNAS and FAM50B DMRs.