单细胞转录组分析显示,晚期孕产妇妇女的乳微环境受到干扰
Hongliang Xie1,2, Yu Lu1,2, Aolin Zhang1,2
1College of Pharmaceutical Sciences & Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Clinical and translational medicine
|December 17, 2025
概括
先进的孕产妇年龄 (AMA) 与由于子宫变化的怀孕风险有关. 这项研究显示,一种新型的PRR15-TGF-β轴在老年人中引起纤维化和决定失败,影响生殖成功.
科学领域:
- 生殖生物学 生殖生物学
- 细胞和分子生物学是细胞和分子生物学.
- 免疫学 免疫学 免疫学
背景情况:
- 先进的孕产妇年龄 (AMA) 与妊娠风险增加有关.
- 在AMA中导致生殖失败的子宫特异性机制,独立于卵细胞和胚胎质量,尚不清楚.
研究的目的:
- 为了描述AMA的女性的树叶微环境.
- 确定老年决策中的关键病理变化和调节途径.
主要方法:
- 综合分析的组织学,有机体建模,和单细胞RNA测序 (scRNA-seq) 的第一季度的决定.
- 在AMA的女性和受控生殖年龄的女性之间的比较.
主要成果:
- 在AMA中的决定体表现出一种病态重塑的微环境,具有异常的细胞状态和亲纤维性特征.
- 过度激活的TGF-β信号驱动纤维化,并损害了树叶层细胞 (DSC) 的分化,包括介质细胞到上皮细胞过渡的失败.
- 发现了一种新型的PRR15-TGF-β轴,其中PRR15抑制导致过度活跃的TGF-β/SMAD信号传递,导致决定失败,纤维化和DSC分化缺陷.
结论:
- 经过失调的TGF-β信号传递和PRR15损失所调节的老化的树叶微环境是AMA生殖失败的关键因素.
- 这项研究确定了一种新型的PRR15-TGF-β轴,它有助于子宫纤维化和决定失败,提供了潜在的诊断和治疗点.
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