Disruption of the Steroid Metabolome in Fish Caused by Exposure to the Environmental Estrogen 17α-Ethinylestradiol

Exposure to environmental estrogens such as 17 alpha-ethinylestradiol (EE2) has been associated with feminization and a decline in fertility of male fish. To investigate the effect of estrogen exposure on steroid homeostasis, we exposed roach (Rutilus rutilus) to EE2 (1-29 ng/L) for 18 days and analyzed steroid profiles in bile and plasma using targeted analyses and in liver and gonadal tissues using mass spectrometry metabolite profiling techniques (metabolomics). Exposure to EE2 resulted in a concentration dependent reduction of estrogens and androgens in bile and plasma of both male and female fish. At 10 ngEE2/L, significant reductions in concentrations of hydroxyprogesterone, androstenedione, 11-hydroxyandrostenedione, and 11-ketotestosterone were detected in the testes metabolome, indicating disruption of steroid biosynthesis upstream of androgen metabolism. Estrogen exposure also resulted in increased biosynthesis of cortisol and cortisone in testes and ovaries, respectively, but did not alter glucocorticoid concentrations in the liver or plasma. This first report on the effect of EE2 exposure on the steroid metabolome in fish tissues suggests that both sex steroid and glucocorticoid pathways are one of the primary targets of estrogen exposure in fish gonads and provides further insights into the mode of action of this endocrine disrupting chemical.