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Home / Equine Research Bank / Mol Reprod Dev / Extracellular Vesicles Derived From Endometrial Stem Cells P...
Molecular reproduction and development2025; 92(8); e70053; doi: 10.1002/mrd.70053

Extracellular Vesicles Derived From Endometrial Stem Cells Preconditioned With PGE2-Reverse Myofibroblast Phenotype in Mare Endometrial Cells: A Novel Anti-Fibrotic Approach.

Abstract: Endometrial fibrosis in mares compromises fertility through aberrant extracellular matrix deposition and sustained myofibroblast activation. Conventional interventions fail to reverse these pathological alterations, necessitating innovative, mechanism-focused therapies. In this study, we pioneered the use of prostaglandin E2 (PGE2) preconditioning of equine endometrial-derived mesenchymal stem cells (ET-eMSCs) and their extracellular vesicles (EVs) to target fibrotic processes directly. ET-eMSCs were isolated from mare endometrial biopsies pretreated with PGE2 to enhance their anti-fibrotic secretome, and EVs were subsequently harvested. In vitro assays demonstrated that PGE2-preconditioned ET-eMSCs and their EVs inhibited α-smooth muscle actin expression, reduced collagen I deposition, and restored key endometrial markers of receptivity and proliferation. These findings establish the first evidence that PGE2-enhanced ET-eMSC-derived EVs can exert anti-fibrotic 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.
© 2025 Wiley Periodicals LLC.
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Publication Date: 2025-08-28 PubMed ID: 40873061DOI: 10.1002/mrd.70053Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research explores how extracellular vesicles derived from endometrial stem cells preconditioned with prostaglandin E2 (PGE2) can reverse fibrosis-related changes in mare endometrial cells, offering a novel therapeutic strategy against endometrial fibrosis.

Background and Rationale

  • Endometrial fibrosis in mares leads to compromised fertility due to excessive extracellular matrix (ECM) deposition and continuous activation of myofibroblasts, the cells responsible for fibrosis.
  • Current treatments fail to reverse these pathological changes, highlighting the need for new therapies directly targeting the underlying mechanisms of fibrosis.
  • Mesenchymal stem cells derived from the equine endometrium (ET-eMSCs) have potential regenerative properties but require enhancement to effectively combat fibrosis.
  • Prostaglandin E2 (PGE2) is known to influence inflammatory and fibrotic processes, making it a candidate molecule to precondition these stem cells to amplify their anti-fibrotic effects.

Study Design and Methods

  • ET-eMSCs were isolated from endometrial biopsies of mares and pretreated with PGE2 to enhance their therapeutic secretions.
  • Following preconditioning, extracellular vesicles (EVs) were collected from these stem cells; EVs are small particles that mediate cell-to-cell communication and can carry regenerative factors.
  • An in vitro model mimicking equine endometrial fibrosis was established to test the effect of PGE2-preconditioned ET-eMSCs and their EVs on pathological markers.
  • Key fibrosis indicators such as α-smooth muscle actin (α-SMA) expression, a marker of myofibroblast activation, and collagen I deposition, a major ECM protein causing fibrosis, were measured.
  • Markers related to endometrial receptivity (important for implantation and fertility) and cell proliferation were also evaluated to assess functional restoration.

Key Findings

  • PGE2-preconditioned ET-eMSCs and their EVs successfully inhibited the expression of α-SMA, indicating suppression of myofibroblast activation.
  • There was a significant reduction in collagen I deposition, showing decreased fibrotic ECM accumulation.
  • Restoration of key endometrial markers involved in receptivity and proliferation suggested recovery of normal endometrial function.
  • This represents the first demonstration that EVs from PGE2-treated ET-eMSCs can exert anti-fibrotic effects in vitro in the context of mare endometrial fibrosis.

Significance and Implications

  • This study highlights a novel regenerative approach using stem cell-derived EVs enhanced by PGE2 preconditioning to reverse fibrosis—an advance over conventional methods.
  • Since endometrial fibrosis is a common cause of infertility in mares, these findings could improve reproductive outcomes in equine veterinary medicine.
  • The research establishes a translational framework, suggesting the potential applicability of this strategy to fibrotic diseases in other species, including humans.
  • It opens new avenues for developing targeted, mechanism-based therapies in reproductive medicine and regenerative treatments for fibrosis beyond the uterus.

Conclusions

  • PGE2 preconditioning enhances the anti-fibrotic secretome of ET-eMSCs, and their extracellular vesicles can modulate key fibrotic markers in mare endometrial cells.
  • This approach provides a promising therapeutic avenue to counteract endometrial fibrosis and restore fertility, with wider translational potential in regenerative medicine.

Cite This Article

APA
Méndez-Pérez L, Ibáñez BO, Rodríguez S, Sen Wong Y, Caamaño D, Navarrete FI, Cabezas J, Mançanares AC, Escudero C, Rodríguez-Álvarez L, Castro FO. (2025). Extracellular Vesicles Derived From Endometrial Stem Cells Preconditioned With PGE2-Reverse Myofibroblast Phenotype in Mare Endometrial Cells: A Novel Anti-Fibrotic Approach. Mol Reprod Dev, 92(8), e70053. https://doi.org/10.1002/mrd.70053

Publication

Molecular reproduction and development
ISSN: 1098-2795
NlmUniqueID: 8903333
Country: United States
Language: English
Volume: 92
Issue: 8
Pages: e70053

Researcher Affiliations

Méndez-Pérez, Lidice
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Ibáñez, Belén O
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
  • Vascular Physiology Laboratory, Group of Research and Innovation in Vascular Health, Basic Sciences Department, Faculty of Sciences, Universidad del Bio-Bio, Concepción, Chile.
Rodríguez, Sebastián
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Sen Wong, Yat
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Caamaño, Diego
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Navarrete, Felipe I
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Cabezas, Joel
  • Facultad de Medicina Veterinaria, Universidad de San Sebastián, Concepción, Chile.
Mançanares, Ana C
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Escudero, Carlos
  • Vascular Physiology Laboratory, Group of Research and Innovation in Vascular Health, Basic Sciences Department, Faculty of Sciences, Universidad del Bio-Bio, Concepción, Chile.
Rodríguez-Álvarez, Lleretny
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.
Castro, Fidel Ovidio
  • Laboratory of Animal Biotechnology, Faculty of Veterinary Sciences, Department of Animal Science, Universidad de Concepción, Chillán, Chile.

MeSH Terms

  • Horses
  • Animals
  • Female
  • Endometrium / metabolism
  • Endometrium / cytology
  • Endometrium / pathology
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / drug effects
  • Dinoprostone / pharmacology
  • Myofibroblasts / metabolism
  • Myofibroblasts / drug effects
  • Myofibroblasts / pathology
  • Myofibroblasts / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Fibrosis
  • Phenotype
  • Cells, Cultured

Grant Funding

  • Financial support was provided by the ANID grants: Fondecyt Regular 1210349 to F.O.C. and 21201557 to L.M-P.

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Citations

This article has been cited 1 times.
  1. Méndez-Pérez L, Wong YS, Ibáñez BO, Martinez-Hormaza I, Rodríguez-Álvarez L, Castro FO. Bidirectional Interaction Between PGE(2)-Preconditioned Mesenchymal Stem Cells and Myofibroblasts Mediates Anti-Fibrotic Effects: A Proteomic Investigation into Equine Endometrial Fibrosis Reversal. Proteomes 2025 Sep 8;13(3).
    doi: 10.3390/proteomes13030041pubmed: 40981201google scholar: lookup
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