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降低NNMT的调节通过抑制复发性自发性流产中的COMP/CD36/ERK1/2轴来影响热囊细胞功能

Jialyu Huang¹, Zhengwei Wan², Jiaqi Li³

¹Center for Reproductive Medicine, Jiangxi Key Laboratory of Reproductive Health, Jiangxi Maternal and Child Health Hospital, Jiangxi Branch of National Clinical Research Center for Obstetrics and Gynecology, Nanchang Medical College, Nanchang, China.

Cellular signalling

|April 24, 2025

概括

尼古丁胺N-甲基转移酶 (NNMT) 对于健康的怀孕至关重要. 复发性自发性流产 (RSA) 中降低的NNMT水平会损害热囊细胞功能,影响胚胎发育并增加吸收率.

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.
母胎界面免疫学母胎界面免疫学

背景情况:

复发性自发性流产 (RSA) 与热囊细胞功能障碍有关.
在RSA中调节热囊细胞功能的分子机制尚未完全理解.

研究的目的:

调查尼古丁胺 N-甲基转移酶 (NNMT) 在复发性自发性流产 (RSA) 中的作用.
阐明NNMT在 trofhoblast 功能中的调节机制.

主要方法:

在RSA和正常怀孕的状组织中量化NNMT和FOXA1表达.
试验室研究涉及NNMT在 trofhoblast 细胞中的敲除,以评估增殖,迁移和入侵.
在体内胚胎吸收率的评估.
基因组甲基化和基因表达的表观遗传学分析 (COMP,CD36,ERK1/2通路).

主要成果:

在RSA状组织中,NNMT水平显著下降.
在体外 (in vitro) 中,NNMT敲除损害了 trofhoblast 增殖,迁移和入侵,并在体内 (in vivo) 增加了胚胎吸收.
作为NNMT的转录调节剂的FOXA1在RSA中也受到下调.
减少的NNMT导致S-adenosyl metionin的积累,促进H3K27甲基化,抑制COMP表达,并影响CD36/ERK1/2通路.

结论:

在母胎界面,NNMT发挥着至关重要的作用.
对NNMT/FOXA1轴的调节失调有助于 trofhoblast 功能障碍和 RSA 病原体.
这项研究为RSA提供了机制性见解和潜在的治疗目标.

关键词:

在 COMP COMP 里面.我们的FOXA1A1 没有NNMTMT的经常发生的自发性流产.热细胞热细胞

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