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.

2,4-二氯苯酚（2,4-DCP）是一种雌激素内分泌干扰物，在水生环境中广泛传播，可能会干扰鱼类的正常生理功能。但是，这种化学物质对性激素合成的影响尚不十分清楚。在本研究中，在受精后20到40天，斑马鱼（Danio rerio）暴露于2,4-DCP（80和160μg/ L）有或没有fadrozole（一种抑制雌二醇合成的芳香酶抑制剂）。然后，确定性别比例，卵黄蛋白原（VTG）和性激素（雄烯二酮（ASD），雌酮（E1），17β-雌二醇（E2），雌三醇（E3），睾丸激素（T）和11-酮睾酮（11- KT））进行了研究。此外，涉及性激素合成的基因的表达（cyp19a1a，cyp19a1b，17β-hsd，11β-hsd和cyp11b）以及cyp19a1a和cyp19a1b启动子中的DNA甲基化进行了分析。结果表明，暴露于2,4-DCP会导致女性偏向比例，增加ASD，E2和VTG的含量，以及E2 / 11-KT的比例，同时降低雄激素（T和11- KT）。cyp19a1a，cyp19a1b，17β-hsd和11β-hsd基因的显着上调可以解释性激素的变化。此外，cyp19a1a的甲基化不足启动子参与了这个过程。值得注意的是，法drozole可以部分减弱2，4-DCP诱导的女性化，并恢复ASD，E2和11-KT的水平。因此，这些结果证明2，4-DCP通过破坏性激素的合成来诱导鱼类中的女性化。