Embryo-derive TNF promotes decidualization via fibroblast activation
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 PGI2 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 CPLA2α phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI2-PPARd-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.
Data availability
All data generated or analysed during this study are included in the manuscript. Source data files are provided for Figures 1-7.
Article and author information
Author details
Funding
National Natural Science Foundation of China (32171114 and 31871511)
- Zeng-Ming Yang
National Key Research and Development Program of China (2018YFC1004400)
- Zeng-Ming Yang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Daria Lizneva, Icahn School of Medicine at Mount Sinai, United States
Ethics
Animal experimentation: All animal protocols were approved by the Animal Care and Use Committee of South China Agricultural University (No. 2021f085).
Version history
- Received: August 24, 2022
- Preprint posted: September 22, 2022 (view preprint)
- Accepted: July 15, 2023
- Accepted Manuscript published: July 17, 2023 (version 1)
- Version of Record published: July 27, 2023 (version 2)
Copyright
© 2023, Chen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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