Correlation of internal exposure levels of polycyclic aromatic hydrocarbons to methylation of imprinting genes of sperm DNA

Abstract

Human exposure to polycyclic aromatic hydrocarbons (PAHs) results in adverse health implications. However, the specific impact of paternal preconception PAHs exposure has not been fully studied. In this study, a total of 219 men aged 24–53 were recruited and an investigation was conducted using a questionnaire requesting information about age, occupation, education, family history, lifestyle, and dietary preferences. Urine and semen samples were examined for the levels of the hydroxyl metabolites of PAHs (OH-PAHs) using ultra-high-performance liquid chromatography–tandem mass spectrometry and spermDNAmethylation by pyrosequencing. The results fromthe correlation analysis using seven OH-PAHs and the average methylation levels of the imprinting genes H19, PEG3, and MEG3 indicated that 1-OHPH is positively correlated with H19/PEG3 methylation levels. We further examined the correlation between each OH-PAH and the methylation levels at the individual CpGs. The results showed 1-OHPH is specifically correlated with CpG4 and CpG6 of the imprinted gene H19, CpG1 and CpG2 of PEG3, and CpG2 ofMEG3; whereas 1-OHP is positively correlated with PEG3 at CpG1. Multivariate regressionmodel analysis confirmed that 1-OHPH and 1-OHP are independent risk factors for the methylation of H19. These data show that sperm DNA imprinting genes are sensitive to adverse environmental perturbations.