Sun Liwei, Zha Jinmiao, Wang Zijian
College of Biological and Environmental Engineering, Zhejiang University of Technology, No. 18 Chaowang Road, Hangzhou 310032, PR China.
Aquat Toxicol. 2009 Jun 4;93(1):83-9. doi: 10.1016/j.aquatox.2009.03.010. Epub 2009 Apr 8.
It is supposed that the estrogenic effects of estrogenic chemicals will be balanced by the presence of other endocrine-disrupting chemicals (EDCs) with different properties. However, little convincing research into this issue has been carried out to date. In the present study, the combined effects of EDCs with estrogenic and antiestrogenic activities were assessed using a 21-day reproduction assay with the Japanese medaka (Oryzias latipes) as an in vivo model. Natural estrogen (17beta-estradiol, E2) and the pharmaceutical substances letrozole and tamoxifen, which are both model antiestrogens, were tested as reference compounds individually and in combination. Exposure to E2 (200 ng/L) alone resulted in significant biological changes in paired fish, including impaired reproductive capacity and plasma vitellogenin induction. Upon coexposure with tamoxifen or letrozole (10, 50 and 250 microg/L), the effects of estrogen on some biomarkers (e.g., plasma vitellogenin concentration) could be neutralized to some extent, but the impairments in reproductive performance were hardly ameliorated or even became more severe. Since reproductive performance is a more holistic parameter with population-level relevance, the possibility that the effects of estrogenic chemicals can be cancelled out by the presence of antiestrogens in aquatic organisms should be questioned. Our observations also illustrate the importance of considering multiple endpoints at different biological levels of organisms for accurate and adequate assessment of the integrated effects of EDCs, especially in environmentally relevant exposure situations.
据推测，具有雌激素活性的化学物质的雌激素效应会被其他具有不同特性的内分泌干扰化学物质（EDCs）所平衡。然而，迄今为止，针对这个问题几乎没有进行过有说服力的研究。在本研究中，以日本青鳉（Oryzias latipes）作为体内模型，通过21天繁殖试验评估了具有雌激素和抗雌激素活性的EDCs的联合效应。天然雌激素（17β-雌二醇，E2）以及作为抗雌激素模型的药物来曲唑和他莫昔芬，分别单独及联合作为参考化合物进行了测试。单独暴露于E2（200 ng/L）会导致配对青鳉出现显著的生物学变化，包括生殖能力受损和血浆卵黄蛋白原诱导。与他莫昔芬或来曲唑（10、50和250 μg/L）共同暴露时，雌激素对某些生物标志物（如血浆卵黄蛋白原浓度）的影响在一定程度上可以被中和，但生殖性能的损害几乎没有得到改善，甚至变得更加严重。由于生殖性能是一个与种群水平相关的更全面的参数，水生生物中抗雌激素的存在能否抵消雌激素化学物质的影响这一可能性值得质疑。我们的观察结果还表明，在准确和充分评估EDCs的综合效应时，尤其是在与环境相关的暴露情况下，考虑生物体不同生物学水平的多个终点的重要性。
