Because of their intrinsic biological activity and ubiquitous environmental occurrence, human pharmaceutical compounds have received increasing attention from health and environmental agencies. In the present study, all-female juvenile rainbow trout (Oncorhynchus mykiss) were exposed to environmentally-realistic concentrations of a mixture of nonsteroidal pharmaceuticals for 42 days, and the effects on plasma levels of sex-steroids and the expression of genes encoding key proteins involved in ovarian development were assessed. Paracetamol, carbamazepine, diclofenac, irbesartan and naproxen were selected, as these have been detected in the Meuse River in Belgium. Fish were exposed to three concentrations of the mixture including the environmental concentration, 10- and 100-times the environmental concentration. Plasma levels of sex-steroid hormones, particularly 11-ketotestosterone, increased in a concentration-dependent way in exposed females. In addition, some key genes involved in ovarian steroidogenesis were significantly overexpressed after 7 days of exposure, such as key genes involved in the maintenance of the ovary. The steady-state mRNA level of genes implicated in germ cell fate were especially affected, such as that of foxl3 which increased by 5 fold at the highest concentration of the mixture. In conclusion, this study highlights that combined occurrence of common pharmaceutical drugs at concentrations present in surface water environments may act as endocrine-disrupting compounds in rainbow trout.

由于其固有的生物活性和普遍存在的环境，人类药物化合物已受到健康和环境机构的越来越多的关注。在本研究中，全雌性少年虹鳟鱼（Oncorhynchus mykiss）暴露于环境现实浓度的非甾体药物混合物中42天，并评估了其对血浆类固醇水平的影响以及编码与卵巢发育有关的关键蛋白的基因表达的影响。选择了扑热息痛，卡马西平，双氯芬酸，厄贝沙坦和萘普生，因为它们是在比利时的默兹河中发现的。鱼暴露于三种浓度的混合物中，包括环境浓度，环境浓度的10倍和100倍。在暴露的女性中，性类固醇激素，尤其是11-酮睾酮的血浆水平以浓度依赖的方式增加。此外，与卵巢类固醇生成有关的一些关键基因在暴露7天后显着过表达，例如参与卵巢保养的关键基因。涉及生殖细胞命运的基因的稳态mRNA水平尤其受到影响，例如foxl3在混合物的最高浓度下增加了5倍。总而言之，这项研究强调了常见药物在地表水环境中的浓度共同作用可能是虹鳟鱼中破坏内分泌的化合物。