下调和上调
滋养层
流产
功能(生物学)
细胞生物学
CD36
男科
医学
化学
药理学
胎盘
怀孕
生物
内科学
胎儿
生物化学
受体
遗传学
基因
作者
Jialyu Huang,Zhengwei Wan,Jiaqi Li,Xiangpeng Xiong,R. Jiang,Bin Yang,Chaoyi Xiong,Hong Chen,Xinxia Wan,Qimei Luo,Yan Zhao,Jiaying Lin,Xiaoyan Ai
标识
DOI:10.1016/j.cellsig.2025.111831
摘要
Recurrent spontaneous abortion (RSA) is closely associated with trophoblast dysfunction, yet the underlying regulatory mechanisms remain poorly understood. Herein, we found a significantly decreased level of nicotinamide N-methyltransferase (NNMT) in RSA villous tissues compared to normal pregnancies. NNMT knockdown suppressed trophoblast proliferation, migration and invasion in vitro, and increased embryo absorption rate in vivo. Upstream of NNMT, FOXA1 was identified as its transcriptional regulator, which was also downregulated in RSA villous tissues. Mechanistically, reduced NNMT led to the accumulation of methyl donor S-adenosyl methionine, thus promoting the methylation of histone H3 at lysine 27. This epigenetic modification further inhibited the expression of cartilage oligomeric matrix protein (COMP), along with its binding to CD36 receptor and subsequent activation of ERK1/2 pathway in trophoblast. Together, our study demonstrates the crucial role of NNMT at the maternal-fetal interface, provides mechanistic insights into the pathogenesis of RSA, and lays a basis for developing targeted therapies.
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