Service Year-Dependent Disruption of Reproductive Hormones and Altered DNA Methylation in Male Firefighters.

Abstract

Firefighters are routinely exposed to combustion-derived toxicants. This exploratory study examined associations between occupational exposure, DNA methylation, and reproductive hormones. Genome-wide methylome profiling using MIRA-seq was performed on pooled blood samples from six male firefighters and four matched controls. Candidate genes were validated by bisulfite sequencing. Jurkat and U937 cells were exposed to benzo[a]pyrene and a phthalate mixture to assess methylation and gene expression. Plasma reproductive hormones were measured in 17 firefighters and 17 matched controls. Firefighters showed 960 differentially methylated genes enriched in reproductive pathways. KLHL17 promoter hypomethylation and increased expression were reproduced in vitro. Hormone analyses demonstrated elevated anti-Müllerian hormone, service year-dependent increases in follicle-stimulating hormone, and reduced testosterone and estradiol. Occupational exposure in firefighters is associated with epigenetic and endocrine alterations potentially affecting reproductive health in firefighters.