2,4-Dichlorophenol (2,4-DCP), an estrogenic
endocrine disruptor, is widely spread in aquatic environments and may interfere with normal physiological functions in fish. However, the influence of this chemical on the synthesis of
sex hormones is not well understood. In the present study, zebrafish (Danio rerio) were exposed to 2,4-DCP (80 and 160 μg/L) with or without
fadrozole (an
aromatase inhibitor which inhibits the synthesis of
estradiol) from 20 to 40 days post fertilization. Then, the sex ratio, the content of
vitellogenin (VTG) and
sex hormones (
androstenedione (ASD),
estrone (E1), 17β-
estradiol (E2),
estriol (E3),
testosterone (T) and 11-ketotestosterone (11-KT)) were studied. Furthermore, the expression of genes involved in synthesis of
sex hormones (cyp19a1a, cyp19a1b, 17β-hsd, 11β-hsd and cyp11b) along with the DNA methylation in cyp19a1a and cyp19a1b promoters was analyzed. The results showed that 2,4-DCP exposure led to female-biased ratio, increased the content of ASD, E2 and VTG, as well as the ratio of E2/11-KT, while decreased the levels of
androgens (T and 11-KT). The sex hormonal change can be explained by the significant up-regulation of cyp19a1a, cyp19a1b, 17β-hsd and 11β-hsd genes. In addition, hypomethylation of cyp19a1a promoter was involved in this process. Notably,
fadrozole can partly attenuate 2,4-DCP-induced
feminization, and recover the levels of ASD, E2 and 11-KT. Thus, these results demonstrate that 2,4-DCP induces
feminization in fish by disrupting the synthesis of
sex hormones.