College of Fisheries and Life Science, Dalian Ocean University, Dalian, Liaoning 116023, China.
Key Laboratory of Environment Controlled Aquaculture, Ministry of Education, 116023, Dalian, China.
Endocrinology. 2021 Oct 1;162(10). doi: 10.1210/endocr/bqab068.
Elucidating the global molecular changes that occur during aromatase inhibitor (AI)- or 17α-methyltestosterone (MT)-induced masculinization and estradiol-17β (E2)-induced feminization is critical to understanding the roles that endocrine and genetic factors play in regulating the process of sex differentiation in fish. Here, fugu larvae were treated with AI (letrozole), MT, or E2 from 25 to 80 days after hatching (dah), and gonadal transcriptomic analysis at 80 dah was performed. The expression of dmrt1, gsdf, foxl2, and other key genes (star, hsd3b1, cyp11c1, cyp19a1a, etc.) involved in the steroid hormone biosynthesis pathway were found be altered. The expression of dmrt1, gsdf, cyp19a1a, and foxl2 was further verified by quantitative polymerase chain reaction. In the control group, the expression of dmrt1 and gsdf was significantly higher in XY larvae than in XX larvae, while the expression of foxl2 and cyp19a1a was significantly higher in XX larvae than in XY larvae (P < .05). AI treatment suppressed the expression of foxl2 and cyp19a1a, and induced the expression of dmrt1 and gsdf in XX larvae. MT treatment suppressed the expression of foxl2, cyp19a1a, dmrt1, and gsdf in XX larvae. E2 treatment suppressed the expression of dmrt1 and gsdf, but did not restore the expression of foxl2 and cyp19a1a in XY larvae. The shared response following AI, MT, and E2 treatment suggested that these genes are essential for sex differentiation. This finding offers some insight into AI or MT-induced masculinization, and E2-induced femininization in fugu.
阐明芳香酶抑制剂 (AI) 或 17α-甲基睾丸酮 (MT) 诱导雄性化和雌二醇-17β (E2) 诱导雌性化过程中发生的全球分子变化，对于理解内分泌和遗传因素在调节鱼类性别分化过程中的作用至关重要。在这里，我们用 AI（来曲唑）、MT 或 E2 处理孵化后 25 至 80 天 (dah) 的河豚幼鱼，并在 80 dah 时进行性腺转录组分析。结果发现，参与类固醇激素生物合成途径的关键基因（star、hsd3b1、cyp11c1、cyp19a1a 等）的 dmrt1、gsdf、foxl2 等表达发生改变。通过定量聚合酶链反应进一步验证了 dmrt1、gsdf、cyp19a1a 和 foxl2 的表达。在对照组中，XY 幼虫的 dmrt1 和 gsdf 表达明显高于 XX 幼虫，而 XX 幼虫的 foxl2 和 cyp19a1a 表达明显高于 XY 幼虫（P <.05）。AI 处理抑制了 XX 幼虫中 foxl2 和 cyp19a1a 的表达，并诱导了 dmrt1 和 gsdf 的表达。MT 处理抑制了 XX 幼虫中 foxl2、cyp19a1a、dmrt1 和 gsdf 的表达。E2 处理抑制了 dmrt1 和 gsdf 的表达，但未恢复 XY 幼虫中 foxl2 和 cyp19a1a 的表达。AI、MT 和 E2 处理后的共同反应表明，这些基因对性别分化至关重要。这一发现为 AI 或 MT 诱导的雄性化和 E2 诱导的雌性化提供了一些启示。
