孕期化物暴露会通过SIRT1-ATF4轴在雌性后代中损害卵巢功能
Yannan Gu1, Yajun Shi2, Bin Wei3
1Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of Obstetrics and Gynecology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of Gynecology, Affiliated Matern & Child Care Hospital of Nantong University, Nantong, Jiangsu 226000, China.
Ecotoxicology and environmental safety
|February 13, 2026
概括
产前暴露于化 (NaF) 损害了女性后代的卵巢储备,通过破坏卵泡发育和促进亡. 使用白醇准SIRT1-ATF4信号提供了针对化物诱导的卵巢功能障碍的潜在治疗策略.
科学领域:
- 生殖毒理学 生殖毒理学
- 环境健康 环境健康
- 分子生物学分子生物学
背景情况:
- 孕妇在怀孕期间暴露于环境因素可能会对后代的生殖健康产生负面影响.
- 怀疑产前化物暴露会导致卵巢功能障碍,但机制尚未完全理解.
研究的目的:
- 调查产前化 (NaF) 暴露对女性后代卵巢功能的影响.
- 阐明化物诱导的卵巢毒性背后的分子机制.
- 评估复星作为一种潜在的治疗干预.
主要方法:
- 建立了一个小鼠模型 (C57BL / 6J) 与产前NaF暴露 (100毫克/升).
- 评估卵巢储备,卵泡成熟和后代的亡.
- 进行了分子分析,包括ATF4,SIRT1,CHOP,BAX/BCL-2通路和H3K9ac水平.
- 利用KGN细胞和白醇治疗进行机制研究和治疗验证.
主要成果:
- 产前的NaF暴露导致卵巢储备减少,卵泡成熟中断,女性后代的卵泡缩增加.
- 纳暴露增加了ATF4和CHOP,降低了SIRT1,并激活了卵巢中的BAX/BCL-2亡途径.
- NaF在ATF4促进体增加了H3K9ac,这表明SIRT1介导的表观遗传调节.
- Resveratrol治疗提高了SIRT1的调节,改善了卵巢功能障碍,并减少了颗粒状细胞的亡.
结论:
- SIRT1-ATF4信号传递是化物诱导的卵巢毒性的中心机制.
- 产前化物暴露会通过SIRT1-依赖ATF4调节的SIRT1-依赖ATF4调节的apoptosis引起卵巢毒性.
- Resveratrol显示了缓解化物暴露引起的环境卵巢功能障碍的治疗潜力.
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