Aryl hydrocarbon receptor antagonists attenuate the deleterious effects of benzo[a]pyrene on isolated rat follicle development

It has been shown that benzo[a]pyrene, a key component of cigarette smoke and an aryl hydrocarbon receptor (AhR) ligand, reduced growth of isolated rat follicles in vitro. However, the mechanism underlying the induced changes in folliculogenesis is unknown. This study proposed that the reported adverse effects of benzo[a]pyrene on follicle growth are mediated through AhR activation. The objective was to investigate the effect of benzo[a]pyrene with and without AhR antagonists (resveratrol or 3',4'-dimethoxyflavone (3,4-DMF)) on follicle growth, oestradiol output, anti-Müllerian hormone (AMH) concentration and cell proliferation in isolated rat follicles cultured in vitro. Benzo[a]pyrene treatment significantly inhibited follicle growth and cell proliferation at concentrations of 1.5 ng/ml and higher (P < 0.05), an effect attenuated by co-incubation with benzo[a]pyrene and resveratrol or 3,4-DMF. A significant decrease in oestradiol (P < 0.05) and AMH output (P < 0.001) by cultured follicles was induced by benzo[a]pyrene treatment, an effect attenuated by co-incubation with 3,4-DMF. The results suggest that the adverse effects of benzo[a]pyrene on follicle growth, steroidogenesis and AMH output are mediated through activation of the AhR. Moreover, AhR antagonists such as resveratrol and 3,4-DMF may have therapeutic benefit in protecting the ovary against the adverse effects of AhR ligands, including benzo[a]pyrene.