Lange Anke, Katsu Yoshinao, Ichikawa Rie, Paull Gregory C, Chidgey Laura L, Coe Tobias S, Iguchi Taisen, Tyler Charles R
School of Biosciences, University of Exeter, Exeter, Devon EX4 4PS, UK.
Toxicol Sci. 2008 Nov;106(1):113-23. doi: 10.1093/toxsci/kfn151. Epub 2008 Jul 24.
Wild roach (Rutilus rutilus) inhabiting UK rivers contaminated with estrogenic effluents from wastewater treatment works show altered sexual development, including intersex, and this can impact negatively on their reproductive capabilities. The molecular events underlying these disruptions in gender assignment, however, are still poorly understood. In this study, two isoforms of aromatase (cyp19a1a and cyp19a1b) were cloned from the roach, and effects of exposure to 17alpha-ethinylestradiol (EE(2)) during early life were determined on the expression of both aromatases and on the estrogen receptors (ERs) (subtypes esr1 and esr2b) and analyzed against effects on the progression of gonadal sex differentiation. Exposure to environmentally relevant concentrations of EE(2) during the critical period of sex differentiation resulted in gonadal feminization and all roach exposed to 4 ng EE(2)/l were females. These effects on gonadal development were associated with alterations in the expression of both esr and cyp19a1 genes in bodies and heads of exposed fish with the most marked effects on the expression of esr1 and cyp19a1b. Our findings show that both aromatase isoforms and both ER subtypes are associated with sexual differentiation in roach, and alterations in their expression can signal for disruptions in sexual development.
栖息在英国被污水处理厂排放的雌激素污染的河流中的野生拟鲤（Rutilus rutilus）出现了包括雌雄同体在内的性发育改变，这会对其繁殖能力产生负面影响。然而，这些性别分化紊乱背后的分子事件仍知之甚少。在本研究中，从拟鲤中克隆出两种芳香化酶同工型（cyp19a1a和cyp19a1b），并确定了幼鱼期暴露于17α-乙炔雌二醇（EE(2)）对这两种芳香化酶以及雌激素受体（ERs）（亚型esr1和esr2b）表达的影响，并分析了其对性腺性别分化进程的影响。在性别分化的关键时期暴露于环境相关浓度的EE(2)会导致性腺雌性化，所有暴露于4 ng EE(2)/l的拟鲤均为雌性。这些对性腺发育的影响与暴露鱼的身体和头部中esr和cyp19a1基因表达的改变有关，其中对esr1和cyp19a1b表达的影响最为显著。我们的研究结果表明，两种芳香化酶同工型和两种ER亚型均与拟鲤的性别分化有关，它们表达的改变可能预示着性发育的紊乱。
