Characteristics of Global Methylation Changes in F1 Mice Sperm DNA Induced by Gestational Arsenic Exposure Are Re-Established in F2 Somatic Cells but Not in F2 Germ Cells

Gestational exposure to chemicals has been reported to transmit epigenetic modifications of germ cells not only to somatic cells but also to the germ cells of the next generation, resulting in adverse effects. Arsenic is one of the environmental chemicals of greatest concern, but it is not precisely clarified whether and how epigenetic modifications of F1 sperm caused by gestational exposure are transmitted to the next generation of somatic cells and germ cells. In the present study, we examined the effects of arsenic exposure during gestation on DNA methylation in germ line and somatic cells of the F2. The DNA methylome of F2 sperm was analyzed by reduced representation bisulfite sequencing (RRBS) and compared to that of F2 liver and testis. We found that F2 liver and testis DNA from the arsenic group exhibited the decrease in global DNA methylation levels and bias of DMC distribution toward hypoDMC observed in F1 sperm DNA which we have previously reported, but F2 sperm DNA did not exhibit those characteristics. These studies suggest that the characteristics of epigenetic modifications in F1 sperm induced by gestational arsenic exposure are reestablished in F2 somatic cells but not in F2 germ cells.