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计算毒理学用于阐明导致胎儿生长限制的PFAS,通过结合和降解IGF1蛋白质来限制胎儿生长

Shimin Tao¹, Yahui Zhou², Xuhui Zhang³

¹Department of Pharmacy, Affiliated Children's Hospital of Jiangnan University, Wuxi, Jiangsu 214023, China.

Environmental science & technology

|November 26, 2025

概括

通过破坏胰岛素样生长因子1 (IGF1) 的稳定性,某些基和多基物质 (PFAS) 破坏胎儿生长. 本研究确定了关键的PFAS及其机制,为发育障碍策略提供了洞察力.

科学领域:

环境毒理学环境毒理学
发育生物学发展生物学
分子毒理学分子毒理学

背景情况:

和多基基物质 (PFAS) 与胎儿生长限制 (FGR) 有关.
不完全理解PFAS诱导的FGR背后的机制.
计算毒理学可以识别环境毒素及其生物点.

研究的目的:

阐明PFASs引起FGR的分子机制.
确定对胎儿发育构成最大风险的特定PFAS.
研究胰岛素样生长因子1 (IGF1) 作为PFAS毒性的潜在媒介.

主要方法:

计算毒理学,包括分子对接和动力学模拟.
在体外实验中使用细胞培养和蛋白质 - 配体结合试验.
分析IGF1蛋白水平和 trofhoblast细胞的增殖.

主要成果:

17种普遍存在的PFAS被确定具有高吸收和低排泄潜力.
PFASs,特别是PFDA,PFOS和PFNS,与IGF1和IGF结合蛋白 (IGFBPs) 结合,破坏PI3K-AKT通路.
PFDA和PFOS显著降低了细胞外IGF1和抑制了热囊细胞增殖,效果通过IGF1补充剂得到改善.

结论:

胰岛素类生长因子1 (IGF1) 是一种直接的分子点,可以调解PFAS诱导的FGR.
perfluorodecanoic 酸 (PFDA), perfluorooctanesulfonate (PFOS) 和 perfluorononanoic 酸 (PFNS) 是 PFAS 相关的 FGR 的关键贡献者.
这些发现为制定预防和治疗与PFAS相关的发育障碍的策略提供了基础.

关键词:

IGF1 IGF1 IGF1 IGF1 IGF1 IGF1 IGF1 IGF1 在PFAS中,有很多方法.关键的化合物关键的化合物胎儿生长限制限制胎儿生长毒性的毒性毒性的毒性

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