Sperm DNA integrity status is associated with DNA methylation signatures of imprinted genes and non-imprinted genes

Purpose To evaluate the association between the DNA methylation of specific genes and sperm DNA integrity status in human sperm samples. Methods A total of 166 semen samples were evaluated (86 controls and 80 cases with impaired sperm DNA integrity). We detected the methylation status of 257 CpG sites among two imprinted genes ( H19 and SNRPN ) and four non-imprinted genes related to male infertility ( MTHFR , GSTM1 , DAZL , and CREM ) by using a targeted next-generation sequencing method. Results Differential methylation was found in 43 CpG sites of the promoters of the six candidate genes. H19 , SNRPN , MTHFR , DAZL , GSTM1 , and CREM contained 22, 12, 1, 4, 0, and 4 differentially methylated CpG sites ( P <0.05), respectively. The imprinting genes were associated with relatively higher rates of differentially methylated CpG sites (28.21% in H19 and 41.38% in SNRPN ) than the non-imprinting genes. One CpG site in H19 remained significant after performing strict Bonferroni correction. Conclusion In this study, we found that different site-specific DNA methylation signatures were correlated with sperm DNA integrity status. Further studies are needed to investigate the specific mechanisms leading to the epigenetic modifications.