在人类子宫内膜 stromal 细胞中,SETD7 通过 FOXO1 依赖的机制来调节树叶衰老
Xiaoying Yu1, Wenwen Hou1, Zhiwen Cao2
1Center for Reproductive Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China.
Journal of assisted reproduction and genetics
|December 10, 2025
概括
与细胞衰老相关的蛋白质SETD7在复发性植入失败 (RIF) 中受到上调,并通过抑制脱细胞化来降低子宫内膜受体性. 准SETD7可能会改善RIF患者的生育结果.
科学领域:
- 生殖医学 生殖医学
- 细胞生物学 细胞生物学
- 分子内分泌学分子内分泌学
背景情况:
- 复发性植入失败 (RIF) 是辅助生殖的一个主要挑战.
- 损害子宫内膜受容性是RIF的一个关键因素.
- 细胞衰老,以细胞循环停止和特定的分泌表型为标志,有助于子宫内膜功能障碍.
研究的目的:
- 为了研究SETD7的作用,一个氨酸特异性甲基转移酶,在调节子宫内膜 stromal 细胞衰老.
- 为了阐明SETD7如何影响子宫内膜中的决定化过程.
- 探索SETD7作为改善RIF中的子宫内膜接受力的潜在治疗标.
主要方法:
- 从RIF患者的子宫内膜组织进行转录组分析,以评估SETD7表达.
- 使用人类子宫内膜层细胞 (hESC) 进行体外研究,以评估SETD7对衰老和决定性标记物的影响 (PRL,IGFBP1).
- 研究AKT-FOXO1信号通路和药理FOXO1抑制对RIF衍生hESCs中脱化的作用.
主要成果:
- 在RIF子宫内膜中,SETD7的表达显著升高,与衰老标志物相关,与决定性标志物相反.
- 在hESC中SETD7过度表达会诱导衰老,并抑制决定化标志物 (PRL,IGFBP1).
- 通过AKT通路,SETD7促进FOXO1酸化,抑制这种酸化部分恢复了RIF衍生的hESCs中的决定化.
结论:
- SETD7是乳头衰老和子宫内膜受容性的关键调节者.
- 升高的SETD7通过扰乱决定化,导致植入失败.
- 在RIF患者中,SETD7代表了增强子宫内膜接受力的潜在治疗标.
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