为雌激素,雌激素和类固醇生成中介的生殖毒性建立不利结果通路网络
Johanna Zilliacus1, Monica K Draskau2, Hanna K L Johansson2
1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Frontiers in toxicology
|April 11, 2024
概括
这项研究对影响哺乳动物生殖的内分泌干扰物 (EDs) 列出了不良结果途径 (AOPs). 它确定了核心知识块,以推进AOP网络 (AOPNs),用于监管评估生殖毒性.
科学领域:
- 毒理学 毒理学 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) 对于内分泌干扰物 (ED) 测试和评估至关重要.
- 为了监管适用性,需要进一步开发AOP框架.
- 已经存在的与雌激素,雄激素和哺乳动物繁殖中的类固醇生成障碍相关的AOP被清单.
研究的目的:
- 确定所有与哺乳动物生殖毒性相关的现有AOPs.
- 确定AOP网络 (AOPN) 开发的AOP之间共享的核心关键事件 (KE).
- 为改善ED评估创建一个全面的AOPN.
主要方法:
- 在AOP-wiki库中进行系统的选和搜索.
- 使用Cytoscape的AOP网络 (AOPN) 的可视化.
- 手动改进以删除不完整的AOP并合并类似的关键事件/关系.
主要成果:
- 在最终的AOPN中包括了42个AOP,重点是生殖毒性.
- 确定了16个子网络,涵盖激素干扰,癌症,生殖系统和生育能力.
- 确定了26个核心KE和11个核心KE关系 (KER),其中19个KE已经在经合组织/美国环保署指南中.
结论:
- 开发的AOPN突出了需要进一步改进的知识差距.
- 这个AOPN可以支持内分泌干扰物的识别和评估.
- 这项研究促进了AOP在生殖毒理学中的监管应用.
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