6PPD和6PPD素通过激活人体相关水平的ERα和GPER来诱导子宫内膜细胞功能障碍
Lei Tang1, Xin Li1, Shi-Ye Zhu1
1College of Environment and Ecology, Hunan Agricultural University, 1 Nongda Road, Furong District, Changsha 410128, China.
Environmental science & technology
|May 14, 2025
概括
轮胎化学物质N-(1,3-dimethylbutyl) -N'-phenyl-p-phenylenediamine (6PPD) 和其 (6PPD-Q) 通过激活雌激素受体 (ERα) 和GPER通路来破坏子宫内膜细胞,在纳米分子水平上构成生殖健康风险.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 内分泌学 在内分泌学.
背景情况:
- 轮胎中的6PPD和6PPD-Q在环境中广泛存在,引发了健康问题.
- 子宫内膜细胞功能障碍是与这些环境污染物相关的潜在风险.
研究的目的:
- 研究6PPD和6PPD-Q对子宫内膜细胞的影响.
- 阐明雌激素受体 (ER) 和G蛋白合雌激素受体 (GPER) 在6PPD/6PPD-Q诱导的子宫内膜功能障碍中的信号通路的作用.
主要方法:
- 光竞争性结合和记者基因测试以评估ER结合和转录活性.
- 调动测试用于评估GPER激活.
- 分子动力学模拟以了解差异激活功率.
- 对细胞增殖,迁移和炎症标志物的分析.
主要成果:
- 6PPD和6PPD-Q可以选择性地结合和激活ERα (LOEC分别为500nm和10nm).
- 这两种化合物都激活了GPER信号 (LOEC 1 nM),而6PPD-Q显示出更高的功效.
- 子宫内膜细胞的增殖,迁移和炎症通过ERα/GPER通路在纳米分子度下受到刺激.
结论:
- 6PPD和6PPD-Q通过ERα和GPER激活诱导子宫内膜细胞功能障碍.
- 这些影响,包括扩散和迁移,发生在环境相关的纳米分子度.
- 这些发现突出了与轮胎衍生的污染物相关的潜在生殖健康风险.
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