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胚胎源 TNF 通过激活成纤维细胞促进蜕膜化。

Embryo-derive TNF promotes decidualization via fibroblast activation.

机构信息

Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of Education, Guizhou University; College of Animal Science, Guizhou University, Guiyang, China.

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

出版信息

Elife. 2023 Jul 17;12:e82970. doi: 10.7554/eLife.82970.

DOI:10.7554/eLife.82970
PMID:37458359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10374279/
Abstract

Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.

摘要

蜕膜化是子宫内膜基质成纤维细胞分化为特化的分泌性蜕膜细胞的过程，对于成功建立妊娠至关重要。蜕膜化的潜在机制仍未明确。由于蜕膜化和成纤维细胞激活具有相似的特征，本研究旨在研究成纤维细胞激活是否参与蜕膜化。在我们的研究中，在妊娠蜕膜和体外蜕膜化中明显检测到成纤维细胞激活相关标记物。成纤维细胞激活下分泌的激活素 A 促进体外蜕膜化。我们表明，子宫腔上皮细胞释放的花生四烯酸可通过 PGI 及其核受体 PPARδ 诱导成纤维细胞激活和蜕膜化。基于妊娠和假孕小鼠之间成纤维细胞激活相关标记物的显著差异，我们发现胚胎来源的 TNF 促进 CPLA 磷酸化和腔上皮细胞中花生四烯酸的释放。在人体外蜕膜化中也检测到成纤维细胞激活。类似的花生四烯酸-PGI-PPARδ-激活素 A 途径在人子宫内膜中保守存在。总之，我们的数据表明，胚胎来源的 TNF 促进 CPLA 磷酸化和腔上皮细胞中花生四烯酸的释放，从而诱导成纤维细胞激活和蜕膜化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/b4f1787049bb/elife-82970-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/a88357d12378/elife-82970-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/93752c59d0c9/elife-82970-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/61ff4175c1f9/elife-82970-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/8f148f111e74/elife-82970-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/5d039af798bc/elife-82970-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/ccb38f1fde1b/elife-82970-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/4c4f28904ef1/elife-82970-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/b4f1787049bb/elife-82970-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/a88357d12378/elife-82970-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/93752c59d0c9/elife-82970-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/61ff4175c1f9/elife-82970-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/8f148f111e74/elife-82970-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/5d039af798bc/elife-82970-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/ccb38f1fde1b/elife-82970-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/4c4f28904ef1/elife-82970-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/10374279/b4f1787049bb/elife-82970-fig8.jpg

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