剖析母亲对雄激素暴露对发育编程的影响,通过准雄激素受体
Haojiang Lu1, Hong Jiang1, Congru Li1
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17177, Sweden.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 30, 2024
概括
在怀孕期间的多囊卵巢综合征 (PCOS) 导致由于高雄激素而导致胎儿损伤. 阻断小鼠和人类细胞中的雄激素受体改善了胎盘发育,并预防了妊娠并发症.
科学领域:
- 生殖生物学 生殖生物学
- 内分泌学 在内分泌学.
- 发育生物学是发展生物学.
背景情况:
- 多囊卵巢综合征 (PCOS) 与怀孕期间母亲的雄激素水平升高有关.
- 这些较高的雄激素是妊娠并发症和不良胎儿结果的危险因素.
- 雄激素对胎盘细胞类型和胎儿发育的特定影响需要进一步研究.
研究的目的:
- 在PCOS小鼠模型中研究高素对胎盘和胚胎发育的影响.
- 探索雄激素受体阻断在缓解PCOS相关妊娠并发症的治疗潜力.
- 阐明基底的细胞和分子机制的雄激素诱导的胎盘功能障碍.
主要方法:
- 通过使用持续的雄激素暴露,建立了一个类似PCOS的小鼠模型.
- 小鼠同时接受了雄激素受体阻断剂 - - 胺胺的治疗.
- 评估了胎盘和胚胎发育,通过全基因组双硫酸盐和RNA测序进行分子分析.
- 人类热细胞器官被用来验证在体外系统中的发现.
主要成果:
- 类似PCOS的小鼠表现出胎盘和胚胎发育受损,导致怀孕中期死亡.
- 富他胺治疗可以预防这些不良表型,包括生殖细胞的特异化.
- 胎盘分析揭示了红叶细胞前体的减少 (可能是由于Cdx2下调) 和syncytiotrophoblasts和鼻状红叶细胞巨细胞的分化受损 (与Gcm1,Synb,Prl3b1下调有关).
- 人类热细胞器官中的雄激素暴露模仿了这些变化,表明热细胞分化受损.
结论:
- 在PCOS中持续的雄激素过量会对胎盘发育和胎儿生长产生不利影响,导致妊娠并发症.
- 抗雄激素受体阻塞证明了治疗潜力,用于管理PCOS相关的怀孕问题.
- 损伤的热囊细胞分化是PCOS相关妊娠并发症的关键细胞机制,提供潜在的治疗点.
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