Aberrant blood DNA methylation reveals reproductive hormone imbalances in firefighters

Constant exposure to toxic combustion byproducts distresses firefighters and puts them at risk of developing adverse health conditions. Epigenetic alternations have been identified as one of the major mechanisms linked to environment-induced diseases. We found DUSP22 which was epigenetically activated in heavy traffic exposure cohort, also showed similar alternations in firefighters, suggesting that some common components in the exposure such as PAH exist could be the major epigenetic modifier in both cohorts. We hypothesize that occupation-related exposure causes aberrant methylation changes in blood and eventually affects health outcome in firefighters. Therefore, we performed a genome wide DNA methylation profiling on firefighter blood samples using methylated CpG island recovery assay with next generation sequencing. We found firefighters, showed significant DNA hypomethylation in a set genes which are functionally related to cancer, organismal injury and abnormalities, reproductive system diseases, and developmental disorders. Methylation changes in the top four genes (TRDR6, KLHL17, PDIA2, and PTCHD3) had been confirmed through bisulfite sequencing. Interestingly, GO-KEEG pathway analyses suggest reproductive system and spermatogenesis related pathway as the top gene network. Blood AMH level of firefighters was 1.43-times higher than that of the non-firefighters Our data, for the first time, showed the constant exposure to firefighting environment induces changes in blood DNA methylation and reproductive hormones, which explain why firefighters suffer certain poor health outcomes. Overall design: Pooled six firefighters versus pooled four non-firefighter controls