假定不良结果途径的发展基于雌性胖头小鱼的生理反应,以模拟雌激素对抗雄激素受体激素剂
Mackenzie L Morshead1, Kathleen M Jensen2, Gerald T Ankley2
1Oak Ridge Institute for Science and Education, US EPA, Great Lakes Toxicology and Ecology Division, Duluth, MN, USA.
Aquatic toxicology (Amsterdam, Netherlands)
|June 24, 2023
概括
像EE2和BPA这样的雌激素受体激活剂可以损害鱼类的繁殖. 这项研究假设一种途径涉及降低类固醇生产,影响雌鱼的卵子成熟和排卵.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 生殖生物学 生殖生物学
背景情况:
- 不良结果途径 (AOPs) 将化学物质暴露与不良影响联系起来.
- 已知雌激素受体 (ER) 激动剂会导致鱼类的生殖问题.
- 在ER激动剂诱导的生殖功能障碍中,早期关键事件尚未得到充分理解.
研究的目的:
- 假设在暴露于ER激动剂的雌性鱼类中生殖能力受损的机制.
- 为了研究17α-乙乙二醇 (EE2) 和双A (BPA) 对鱼类繁殖的影响.
- 为了对比ER激动剂的作用与雄激素受体 (AR) 激动剂 (17β-博,TRB) 的作用.
主要方法:
- 成熟的肥头小鱼被暴露在EE2,BPA,TRB或混合物中长达14天.
- 测量了17β-雌激醇和维原素 (VTG) 的血度.
- 对蛋产量的评估影响.
主要成果:
- EE2,BPA和TRB的暴露减少了血中的17β-雌二醇.
- TRB减少了VTG,而EE2/BPA单独或混合物并没有显著影响VTG.
- 只有低剂量的EE2 (1 ng/L) 和BPA (10 μg/L) 没有影响蛋的产量.
结论:
- 假设的AOP:ER激动剂可能会降低诱导成熟的类固醇,损害卵细胞成熟和排卵.
- 潜在的机制包括膜ER激活的负反或直接抑制作用.
- 这些事件可能会导致雌性鱼的不良生殖结果.
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