疾病预防控制中心42缺乏导致子宫内膜 stromal 细胞衰老在反复植入失败导致的植入失败
Xinyi Tang1,2, Yingchun Zhu1,2, Zhiwen Cao1,2
1Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Human reproduction (Oxford, England)
|November 2, 2024
概括
细胞分裂周期42 (CDC42) 缺陷的子宫内膜导致老化和衰退的决定在患者的复发性植入失败 (RIF). 这种功能障碍与Wnt信号通路的激活有关,这表明了潜在的治疗点.
科学领域:
- 生殖生物学和医学生殖生物学和医学
- 细胞衰老 细胞衰老
- 子宫受体性的分子机制
背景情况:
- 在患有复发性植入失败 (RIF) 的年轻患者中观察到子宫内膜衰老.
- 细胞分裂周期42 (CDC42) 的下调,是衰老相关疾病中的关键分子,在RIF子宫内膜中被发现.
研究的目的:
- 调查是否会导致子宫内膜层瘤的CDC42下调导致RIF患者的衰老.
- 阐明将CDC42缺乏,子宫内膜衰老和RIF联系在一起的潜在机制.
主要方法:
- 来自71名肥沃对照和37名RIF患者的子宫内膜样本的分析.
- 使用初级子宫内膜层细胞 (EnSCs) 的体外研究与CDC42敲击.
- 对衰老标志物,纤维化,决定化标志物 (PRL,IGFBP1) 和体外植入模型的评估.
- 用RNA测序和生物信息分析来确定下游的信号通路.
- 用Wnt信号抑制剂 (XAV-939) 进行治疗,以评估治疗潜力.
主要成果:
- RIF患者表现出子宫内膜 stromal 衰老,纤维化和CDC42缺陷的增加.
- 在EnSCs中,CDC42的淘汰诱导过早衰老,原沉积,以及受损的决定化和 trofhoblast 受容性.
- 转录组分析显示,Wnt信号通路在CDC42缺陷下游的激活.
- 阻断Wnt信号传递部分逆转衰老,并改善了决定化和热囊细胞入侵.
结论:
- 疾病预防控制中心42缺乏是子宫内膜层衰老和RIF中的决定性缺陷的关键驱动因素.
- 该机制涉及异常的Wnt信号激活.
- Wnt信号抑制剂通过缓解子宫内膜衰老,显示出作为RIF治疗策略的希望.
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