为发育死亡率和怀孕损失绘制化学基因相互作用的地图.
Syed Hassan Bukhari1, Amrita Nagasuri1, Boris Oskotsky1
1Bakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
medRxiv : the preprint server for health sciences
|November 24, 2025
概括
环境暴露可以通过在发育过程中破坏关键基因而导致怀孕流产. 化学基因图谱 (CGA) 工具有助于识别这些化学基因相互作用和脆弱的发育时期.
科学领域:
- 生殖毒理学 生殖毒理学
- 发育生物学是发展生物学.
- 环境健康 环境健康
背景情况:
- 流产影响10-15%的怀孕,受遗传和环境因素的影响.
- 现有的资源缺乏通过妊娠时间,母胎区或致命性背景对化学基因相互作用的组织.
研究的目的:
- 弥合了解与流产相关的化学基因相互作用的差距.
- 根据发育背景组织化学基因证据的资源.
主要方法:
- 合并的不耐受基因和比较毒基因组学数据库数据.
- 创建了一个由928个致命性相关基因和4,000种化学物质组成的网络.
- 开发了化学基因图谱 (CGA) 应用程序,用于生成假设和临床翻译,具有四个过器.
主要成果:
- 确定了五个临床重要基因 (F5,F2,AURKB,PADI6,FOXD1),与重复性妊娠丧失 (RPL) 有关.
- 证明了影响这些基因的双A (BPA) 和[a] (B[a]P) 的差异性暴露基因模式.
- 显示了基因表达,甲基化,凝血通路和胎盘功能的破坏.
结论:
- 具有功能丧失不耐受性的基因,特别是在新陈代谢和心血管系统中,容易受到环境破坏的影响.
- 环境暴露会影响重要的发育窗口,如植入,胎盘发育和早期器官生成.
- 该CGA平台提供了一个可扩展的模型,用于调查导致发育致死性的化学基因相互作用.
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