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该METTL3-PGR-WNT4轴对人类子宫内膜层细胞决定性决定至关重要

Yu-Qi Hong¹, Shi Tang¹, Xiao-Qi Yang¹

¹College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

The FEBS journal

|July 25, 2025

概括

甲基转移酶类3 (METTL3) 对于人类的决定性至关重要. 降低的METTL3通过通过孕激素受体 (PGR) 途径降低WNT4的调节,损害了胚胎植入.

科学领域:

生殖生物学生殖生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
植入的分子机制的植入.

背景情况:

子宫m6对于小鼠胚胎植入至关重要的一种修改.
人类决定化中m⁶A的作用尚未完全理解.
经常出现的植入失败突出了研究子宫内膜因素的必要性.

研究的目的:

调查甲基转移酶类3 (METTL3) 在人类决定化中的作用.
阐明涉及METTL3在子宫内膜 stromal 细胞中的分子途径.
为了确定复发性植入失败的潜在治疗点.

主要方法:

在女性中对子宫内膜METTL3水平的分析复发性植入失败.
在人类子宫内膜层细胞 (HESCs) 中,小干扰RNA (siRNA) 介导的METTL3的淘汰.
评估决定化的标记物,包括WNT4和孕激素受体 (PGR) 表达.
研究m6在PGRmRNA的5'未翻译区域 (5'-UTR) 的修改.

主要成果:

复发性植入失败的妇女的子宫内膜中METTL3显著下降.
在HESC中,METTL3的淘汰影响了决数化,主要是通过降低WNT4.4的调节.
METTL3通过m6对PGRmRNA的修饰来积极调节PGR蛋白表达.
在PGR的下游,WNT4作为METTL3.3的次要目标.

结论:

METTL3-PGR-WNT4通路对于人类的决策至关重要.
这种途径的失调有助于反复发生的植入失败.
这项研究为人类决定性的分子基础提供了新的见解,并提出了潜在的治疗途径.

关键词:

在METTL3中,METTL3是METTL3的第一个类型.这就是WNT4的原因.个人化的决定性.孕激素受体的受体是什么孕激素受体经常发生的植入失败.

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