Low Levels of Perfluorooctanoic Acid Exposure Activates SteroidHormone Biosynthesis through Repressing Histone Methylation in Rats

Perfluorooctanoic acid (PFOA) is a persistentorganic pollutant, which has endocrine-disrupting properties andcan interfere with the synthesis and secretion of testicular steroidhormones, but the underlying molecular mechanisms are still notfully understood. In this study, we investigated the effects of lowdoses of PFOA exposure on testicular steroidogenesis in rats andrevealed the role of histone modifications. It was found that theserum levels of progesterone, testosterone, and estradiol weresignificantly increased after 0.015 and 0.15 mg/kg of PFOAexposure, and the expression ofStar, a key rate-limiting gene, wasup-regulated, while other steroidogenic genesCyp11a1,Hsd3b,Cyp17a1, andHsd17bwere down-regulated. In addition, the levelsof multiple histone modifications (H3K9me1/2/3 and H3K9/18/23ac) were all significantly reduced by PFOA in rat testis. Histone H3K9 methylation is associated with gene silencing, while histoneacetylation leads to gene activation. ChIP analysis further showed that H3K9me1/3 was significantly decreased in the promoterregion ofStar, while H3K18ac levels were down-regulated in other gene promoters. Accordingly, we suggest that low-level PFOAenhances StAR expression through the repression of H3K9me1/3, which stimulates steroid hormone production in rat testis. Theseresults are expected to shed new light on the molecular mechanisms by which low-dose PFOA disturbs male reproductive endocrinefrom an epigenetic aspect and may be useful for human health risk assessment regarding environmental PFOA exposure.