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商业用抗雄激素氟他胺对雄性虹彩鱼(Melanotaenia fluviatilis)生殖生物标志物的影响。

Effects of the commercial antiandrogen flutamide on the biomarkers of reproduction in male Murray rainbowfish (Melanotaenia fluviatilis).

机构信息

Commonwealth Scientific and Industrial Research Organisation Land and Water, Glen Osmond, Adelaide, South Australia, Australia; School of Agriculture, Food and Wine, Waite Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.

出版信息

Environ Toxicol Chem. 2014 May;33(5):1098-107. doi: 10.1002/etc.2524. Epub 2014 Mar 21.

DOI:10.1002/etc.2524
PMID:24453069
Abstract

The endocrine responses in male Murray rainbowfish (Melanotaenia fluviatilis) were evaluated after exposures to biologically active concentrations of the nonsteroidal pharmaceutical, flutamide. Fish were exposed to nominal concentrations of 125 µg/L, 250 µg/L, 500 µg/L, and 1000 µg/L of flutamide for 7 d, after which plasma vitellogenin concentration; brain aromatase activity; and hepatic expression of the genes for vitellogenin, choriogenin, and androgen and estrogen receptors were assessed. Qualitative assessment of the testes of the fish exposed to flutamide exhibited hindrance in the transformation of spermatogonia to spermatozoa and increased testicular anomalies, such as multinucleated and pyknotic cells and interstitial fibrosis. An increase in the hepatosomatic index with respect to the controls was noted after treating the fish with flutamide at all concentrations. Vitellogenin was induced in plasma in the 1000 µg/L flutamide group. The activity of aromatase in the brain declined significantly after exposures to flutamide at all concentrations. Males exposed to 1000 µg/L of flutamide showed a downregulation in the genes encoding androgen receptors α and β. The expression of the gene for the estrogen receptor α was induced and of vitellogenin was downregulated after treatment with 250 µg/L to 1000 µg/L of flutamide. The results suggest that 7-d exposures to 125 µg/L to 1000 µg/L flutamide can impair the reproductive endocrine system in male Murray rainbowfish at multiple levels by an antiandrogenic mode of action.

摘要

雄性墨瑞雷彩虹鱼(Melanotaenia fluviatilis)暴露于生物活性浓度的非甾体药物氟他胺后,其内分泌反应得到了评估。鱼被暴露于氟他胺的名义浓度为 125μg/L、250μg/L、500μg/L 和 1000μg/L 下 7 天,之后评估了血浆卵黄蛋白原浓度、脑中芳香酶活性以及肝脏中卵黄蛋白原、绒毛膜蛋白和雄激素和雌激素受体基因的表达。暴露于氟他胺的鱼的睾丸的定性评估显示,精原细胞向精子的转化受阻,并增加了睾丸异常,如多核和固缩细胞以及间质纤维化。在用氟他胺处理鱼后,所有浓度组的肝体比均增加。在 1000μg/L 氟他胺组中,血浆中诱导产生了卵黄蛋白原。在所有浓度下暴露于氟他胺后,脑中芳香酶的活性显著下降。暴露于 1000μg/L 氟他胺的雄性鱼,编码雄激素受体 α 和 β 的基因下调。雌激素受体 α 的基因表达被诱导,而 250μg/L 至 1000μg/L 的氟他胺处理后,卵黄蛋白原的基因表达被下调。结果表明,7 天暴露于 125μg/L 至 1000μg/L 的氟他胺可通过抗雄激素作用模式在多个水平上损害雄性墨瑞雷彩虹鱼的生殖内分泌系统。

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