Programm MGU Mensch-Gesellschaft-Umwelt, Department of Environmental Sciences, University of Basel, Vesalgasse 1, Basel 4051, Switzerland.
Environ Toxicol. 2014 Feb;29(2):199-206. doi: 10.1002/tox.20786. Epub 2011 Nov 24.
A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17β-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development.
水生环境中存在的一系列化学物质具有通过模拟或拮抗激素的作用,或通过改变激素的合成和代谢来影响内分泌功能和性发育的潜力。本研究的目的是评估干扰性激素合成的化学物质的影响是否可能通过调节类固醇和胰岛素样生长因子 (IGF) 系统来影响早期卵巢发育的调节。为此,对幼年褐鳟(Salmo trutta fario)的卵巢进行了离体培养,并在 2 天内分别用 1,4,6-androstatriene-3,17-dione (ATD,一种特定的芳香酶抑制剂)、prochloraz(一种咪唑类杀真菌剂)或三丁基锡 (TBT,一种持久性有机污染物) 进行处理。此外,对幼年雌性褐鳟进行了为期 2 天的体内暴露实验,用 prochloraz 或 TBT 进行处理。比较了体外和体内卵巢芳香酶 (CYP19)、负责雌激素产生的 IGF1 和 2 的基因表达。此外,还评估了从体外卵巢培养物中产生的 17β-雌二醇 (E2) 和睾酮 (T)。ATD 的体外暴露抑制了卵巢 E2 的合成,而 T 的水平则积累。然而,ATD 并没有影响体外 cyp19、igf1 或 igf2 的表达。Prochloraz 的体外暴露抑制了卵巢 E2 的产生,但不影响 T 的水平。此外,prochloraz 在体外和体内暴露时均上调了 igf1 的表达。TBT 暴露并未改变 E2 或 T 的体外合成。然而,体内暴露于 TBT 下调了 igf2 的表达。结果表明,幼年褐鳟卵巢中 E2 产生的抑制可能不会直接影响 cyp19 和 igf 基因表达。因此,我们认为这些测试化学物质可能以独立的方式干扰类固醇和 IGF 系统,并且根据已发表的文献,可能导致内分泌功能障碍和性发育改变。