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

OBJECTIVES: Firefighters are routinely exposed to combustion-derived toxicants. This exploratory study examined associations between occupational exposure, DNA methylation, and reproductive hormones. METHODS: 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. RESULTS: 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. CONCLUSIONS: Occupational exposure in firefighters is associated with epigenetic and endocrine alterations potentially affecting reproductive health in firefighters.