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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\n                    <jats:sub>2<\/jats:sub>\n                    and its nuclear receptor PPAR\u03b4. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI\n                    <jats:sub>2<\/jats:sub>\n                    -PPAR\u03b4-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.\n                  <\/jats:p>","DOI":"10.7554\/elife.82970","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T07:40:13Z","timestamp":1689579613000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.82970","source":"Crossref","is-referenced-by-count":21,"title":["Embryo-derive TNF promotes decidualization via fibroblast activation"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5127-0236","authenticated-orcid":true,"given":"Si-Ting","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02wmsc916","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of Education, Guizhou University; 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