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In this study, we pioneered the use of prostaglandin E2 (PGE2) preconditioning of equine endometrial\u2010derived mesenchymal stem cells (ET\u2010eMSCs) and their extracellular vesicles (EVs) to target fibrotic processes directly. ET\u2010eMSCs were isolated from mare endometrial biopsies pretreated with PGE2 to enhance their anti\u2010fibrotic secretome, and EVs were subsequently harvested. In vitro assays demonstrated that PGE2\u2010preconditioned ET\u2010eMSCs and their EVs inhibited \u03b1\u2010smooth muscle actin expression, reduced collagen I deposition, and restored key endometrial markers of receptivity and proliferation. These findings establish the first evidence that PGE2\u2010enhanced ET\u2010eMSC\u2010derived EVs can exert anti\u2010fibrotic effects in an in vitro model of equine endometrial fibrosis. This study provides a robust translational framework for developing targeted regenerative therapies for fibrotic diseases across species, with potential applications in human reproductive medicine.<\/jats:p>","DOI":"10.1002\/mrd.70053","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T05:13:43Z","timestamp":1756358023000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular Vesicles Derived From Endometrial Stem Cells Preconditioned With PGE2\u2010Reverse Myofibroblast Phenotype in Mare Endometrial Cells: A Novel Anti\u2010Fibrotic Approach"],"prefix":"10.1002","volume":"92","author":[{"given":"Lidice","family":"M\u00e9ndez\u2010P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science Universidad de Concepci\u00f3n Chill\u00e1n 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