Paternal exposure to arsenic and sperm DNA methylation of imprinting gene Meg3 in reproductive-aged men

摘要

Background Prenatal exposure to arsenic and mercury have been associated with adverse pregnancy outcomes that might be in part mediated by dynamic modification of imprinting gene that are emerging mechanism. Objectives The objective of this study was to examine the impacts of paternal exposure to arsenic and co-exposure to arsenic and mercury on human sperm DNA methylation status of imprinting genes, respectively.Methods A total of 352 male subjects (23-52 years old) were recruited and demographic data were obtained through questionnaires. Urinary arsenic and mercury levels were measured using hydride generation-atomic fluorescence spectrometer. Multivariate regression model was employed to investigate the relationship between urinary arsenic levels and sperm DNA methylation status at H19, Meg3 and Peg3, measured by pyrosequencing, and evaluating the interaction with mercury. Results After adjusting potential confounds factors by multivariate regression model, the results indicated a significantly positive relationship between urinary arsenic levels and the methylation status of Meg3 at both mean level (β= +0.125, p< 0.001) and all individual CpGs, i.e., CpGl (β= +0.094, p<0.001), CpG2 (β=+0.132, p< 0.001), CpG3 (β=+0.121, p<0.001), CpG4 (β=+0.142, p< 0.001), CpG5 β=+0.111, p<0.001), CpG6 (β= +0.120, p<0.001), CpG7 (β= +0.143, p<0.001), CpG8 (β= +0.139, p<0.001) of Meg3 DMRs. The interaction effects analysis indicated the interaction effects of arsenic and mercury on Meg3 were not existing. Conclusions Paternal nonoccupational exposure to arsenic induces the altered DNA methylation status of Meg3 in human sperm DNA. In addition, the interaction effects of arsenic and mercury on Meg3 were not existing. These findings would implicate the sensibility of sperm epigenome for environmental pollutions.