TDCIPP 干扰了果性巨细胞的功能,通过铁死介导的 DNA 损伤诱导流产
Yongbo Zhao1, Jiani Sun2, Hanyu Rao2
1Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China.
Journal of hazardous materials
|January 29, 2026
概括
三1,3-二二) 酸盐 (TDCIPP) 暴露与自发性流产有关. 这种化学物质在状巨细胞中触发铁,导致炎症和胚胎再吸收,但谷可以防止这种损伤.
科学领域:
- 环境健康 环境健康
- 生殖毒理学 生殖毒理学
- 免疫学 免疫学 免疫学
背景情况:
- 三1,3-二-2-) 酸盐 (TDCIPP) 是一个广泛存在的环境污染物.
- 虽然TDCIPP的生殖毒性是已知的,但其对怀孕维持和机制的影响尚不清楚.
研究的目的:
- 调查TDCIPP对怀孕维持的影响.
- 为了阐明TDCIPP诱导的怀孕流产的潜在分子机制.
主要方法:
- 在人类决定中检测TDCIPP.
- 孕期暴露小鼠的TDCIPP.
- 分析了状巨细胞表型,铁亡标记物 (GPX4,GSH),DNA损伤,cGAS/STING通路激活和IFN-β表达.
- 对胚胎再吸收率的评估.
- 与谷氨 (GSH) 补充剂的干预.
主要成果:
- 在人类 decidua 中发现了 TDCIPP,并与自发妊娠流产有关.
- 在小鼠中,TDCIPP暴露诱导了一种亲炎性果性巨细胞表型,并增加了胚胎再吸收.
- TDCIPP抑制了GPX4和GSH,引发了巨细胞铁,DNA损伤,cGAS/STING激活和IFN-β的产生.
- 补充GSH可以抵消ferroptosis,DNA损伤,衰老,并减少胚胎再吸收.
结论:
- 暴露于TDCIPP与通过ferroptosis驱动的机制导致自发妊娠流产有关.
- 通过铁亡,TDCIPP会诱导 decidua 中的炎症和细胞损伤,导致怀孕流产.
- 铁亡是一种潜在的治疗标,可以缓解由TDCIPP等环境污染物引起的妊娠流产.
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