Genome-wide DNA methylation analysis in the testes of F2 male mice gestationally exposed to arsenic

<p>It has been reported that exposure to environmental chemicals has adverse effects on the health of the next generation. However, the details of these effects have not been fully elucidated. We are currently analyzing the mechanisms of the effects of arsenic on the next generation. We have found genome-wide methylation changes in sperm DNA of arsenic group F2 born from F0 mice gestationally exposed to arsenic. In this study, we investigated the effect of gestational arsenic exposure on F2 testis DNA by genome-wide DNA methylation analysis to search for factors that influence DNA methylation changes in F2 sperm. C3H mice F0 were given water or 85 ppm sodium arsenic water ad libitum at 8-18 days of gestation. Testes were obtained from the F2 males (control and arsenic groups) and their DNA methylation status was analyzed by Reduced representation bisulfite sequencing (RRBS) method. The results of RRBS analysis showed genome-wide DNA hypomethylation in the F2 testis of the arsenic group. When we annotated all identified CpGs and differentially methylated cytosines (DMCs), the occurrence of DMCs whose methylation were changed by more than 10% in the arsenic group compared to the control group was particularly high in LINEs as in the case of sperm. These results suggest that LINE is a region where DNA methylation is easily to be altered by arsenic in testes and sperm. In addition, some of the genes with altered promoter methylation were related to spermatogenesis. We will continue to investigate how these genes affect spermatogenesis.</p>