持续的Wnt信号影响了试管婴儿胚胎植入和后代代谢
Yanping Jia1, Yingdong Liu1, Yanhe Li1
1Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Science bulletin
|May 29, 2025
概括
持续的Wnt信号阻碍了体外受精 (IVF) 胚胎植入,并导致后代代谢问题. 抑制Wnt信号改善了IVF胚胎的发育,并改善了后代的代谢异常.
科学领域:
- 生殖生物学 生殖生物学
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 辅助生殖技术 (ART) 与植入失败和后代代谢问题有关.
- 与ART相关的并发症背后的机制尚未完全理解.
- 在早期发育和植入过程中,Wnt信号发挥着至关重要的作用.
研究的目的:
- 调查持续Wnt信号在植入周边胚胎中的作用.
- 探索Wnt信号对基因组修饰和基因表达的影响.
- 确定Wnt抑制是否可以改善试管婴儿胚胎发育和后代健康.
主要方法:
- 使用小鼠模型进行体外受精 (IVF) 胚胎植入.
- 在表皮质细胞中分析了基因组修饰 (H3K27ac,H3K27me3) 和基因表达 (Otx2).
- 在周植入阶段服用Wnt抑制剂IWP2.
- 评估植入率,子宫内发育和后代代谢参数.
- 检查了人类植入前胚胎发育和多能性状态过渡.
主要成果:
- 持续的Wnt激活破坏了原始的多能性过渡,并抑制了Otx2的表达.
- 通过IWP2抑制Wnt,使表皮质细胞中的基因修饰和基因表达正常化.
- 抑制Wnt显著增强了IVF胚胎植入和子宫内发育.
- 抑制Wnt可以改善IVF过程中产生的后代的代谢异常.
- 抑制Wnt可以改善人类植入周围胚胎的发育和保持原始多能性.
结论:
- 持续的Wnt信号是试管婴儿胚胎植入失败和随后的代谢障碍的关键因素.
- 在植入前阶段针对Wnt信号提供了一种治疗策略.
- 抑制Wnt可以改善胚胎发育和长期后代健康结果.
- 这项研究揭示了预防ART相关并发症的新机制.
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