暴露会导致铁死,通过非正规的MBOAT1通路诱导无法解释的流产
Yi Sun1, Wenxin Huang1, Qigang Fan1
1Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Nature communications
|December 11, 2025
概括
高 (Li) 含量与无法解释的流产 (UM) 有关,因为它会导致胎盘铁亡. 在小鼠中补充Mboat1可降低铁亡和减轻流产,识别Li暴露风险.
科学领域:
- 生殖毒理学 生殖毒理学
- 环境健康 环境健康
- 生物化学 生物化学
背景情况:
- 无法解释的流产 (UM) 对全球人类生殖构成了重大挑战.
- 来自电池的 (Li) 进入环境和人体,其对生殖健康的影响在很大程度上尚未被探索.
- 越来越多的环境污染需要了解其对生殖结果的影响.
研究的目的:
- 调查暴露,胎盘铁亡和无法解释的流产之间的关联.
- 阐明引发胎盘损伤和流产的分子机制.
- 为了确定潜在的治疗目标,以减轻引起的生殖毒性.
主要方法:
- 对血清水平,状组织铁亡以及无法解释的流产发生率的相关分析.
- 在体内小鼠模型暴露于高水平以评估胎盘功能和流产诱导.
- 细胞内膜网膜 (ER) 应激,基因转录 (METTL1,MBOAT1),mRNA修饰 (m7G) 和铁亡途径 (GPX4独立) 的分子分析.
主要成果:
- 较高的血清水平与状组织铁亡的增加和无法解释的流产相关.
- 在小鼠中,暴露诱导了胎盘铁和流产,通过降低ER水平,抑制METTL1和MBOAT1转录,并降低MBOAT1mRNA稳定性.
- 诱导的铁灭亡发生在GPX4和Mboat1补充剂独立的小鼠中,抑制了胎盘铁灭亡和减轻了流产.
结论:
- 暴露对健康构成重大风险,有助于通过胎盘铁亡导致无法解释的流产.
- 这项研究揭示了一种新的GPX4独立铁亡途径,由ER压力和改变的mRNA修饰介导.
- Murine Mboat1可以作为预防或治疗引起的生殖损害的潜在治疗标.
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