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Veterinary medicine and science2026; 12(2); e70685; doi: 10.1002/vms3.70685

Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment.

Abstract: Equine chronic degenerative endometritis (CDE) is a progressive process characterized by endometrial fibrosis that could be responsible for alterations of uterine environment and foetal-maternal communication. Objective: The aim of this study was to try to restore this communication by intrauterine administrations of amniotic cell-derived extracellular vesicles (AMC-EVs) in a case series. Methods: Twelve mares were selected on the basis of their reproductive history of early embryonic loss or abortion and clinical suspicion of CDE subsequently verified with histopathological examination of endometrial biopsies. Methods: Gynaecological and ultrasound examinations and histopathological examination of endometrial biopsies were performed. Mares were divided into two groups: Seven mares in Group 1 received a single treatment cycle (corresponding to two intrauterine AMC-EV administrations), whereas five mares of Group 2 received two treatment cycles (corresponding to four intrauterine AMC-EV administrations). Each administration was of 20 billion AMC-EVs diluted in 50 mL of sterile saline solution. Results: Eleven mares were able to establish pregnancy after the treatment with AMC-EVs without significant difference in pregnancy outcomes between one or two treatment cycles (six out of seven mares of Group 1 and all mares of Group 2 were pregnant), suggesting that one cycle may be sufficient. The histological condition of their endometrium did not show any improvement in Kenney-Doig classification, meaning AMC-EVs did not exert regenerative activity but probably contributed to re-establishing a functional paracrine interaction between embryo and maternal tissues. Conclusions: This study has the limitation of the small number of animals enrolled and the lack of a control group. However, considering the large number of past artificial insemination attempts for each animal enrolled in this study, each mare could be considered self-control. Conclusions: It would seem possible that AMC-EVs supported and enhanced foetal-maternal communication that was compromised by CDE.
© 2025 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.
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Publication Date: 2026-02-05 PubMed ID: 41641829PubMed Central: PMC12874493DOI: 10.1002/vms3.70685Google Scholar: Lookup
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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 study investigates the use of extracellular vesicles derived from amniotic mesenchymal stromal/stem cells (AMC-EVs) as a treatment for equine chronic degenerative endometritis (CDE), a condition causing uterine fibrosis and impaired communication between the embryo and maternal tissue.
  • The research involved intrauterine administration of AMC-EVs to mares with a history of reproductive failure, evaluating pregnancy outcomes and uterine tissue condition post-treatment.

Background

  • Equine Chronic Degenerative Endometritis (CDE): CDE is a progressive uterine disease characterized by fibrosis of the endometrium, which disrupts the uterine environment and the crucial communication between foetus and mother.
  • Clinical Significance: CDE is linked to early embryonic loss and abortion, severely impacting fertility in mares.
  • Current Treatment Challenges: Traditional therapies have limited success in restoring uterine functionality or improving pregnancy outcomes in affected mares.
  • Role of AMC-EVs: Extracellular vesicles derived from amniotic mesenchymal stromal/stem cells have been suggested to play a paracrine role, potentially restoring communication within the uterine environment.

Methods

  • Subject Selection: Twelve mares were selected based on reproductive histories marked by early embryonic losses or abortion and suspected CDE confirmed through histopathological exams of endometrial biopsies.
  • Diagnostic Procedures:
    • Gynaecological examinations
    • Ultrasound evaluations
    • Histopathological analysis using Kenney-Doig classification for endometrial tissue assessment
  • Grouping and Treatment:
    • Seven mares (Group 1) received a single treatment cycle: two intrauterine administrations of AMC-EVs
    • Five mares (Group 2) received two treatment cycles: four intrauterine administrations in total
    • Each administration contained 20 billion AMC-EVs diluted in 50 mL sterile saline solution

Results

  • Pregnancy Outcomes:
    • Eleven out of twelve mares established pregnancy post-treatment, indicating a high success rate.
    • There was no significant difference in pregnancy success between mares treated with one or two cycles—six of seven in Group 1 and all five in Group 2 became pregnant.
    • This suggests that a single treatment cycle may be adequate for therapeutic effect.
  • Histopathological Findings:
    • No significant improvement in endometrial fibrosis as measured by the Kenney-Doig classification was observed after AMC-EV treatment.
    • This implies that the extracellular vesicles did not promote tissue regeneration or reversal of the fibrosis.
  • Mechanism Hypothesis: AMC-EVs likely helped restore functional paracrine communication between embryo and maternal tissue, despite no observable structural uterine improvement.

Conclusions and Limitations

  • Potential Therapeutic Value: AMC-EVs might support and enhance foetal-maternal communication impaired due to CDE, leading to improved pregnancy outcomes even without structural tissue regeneration.
  • Self-Control Design: Each mare’s prior unsuccessful inseminations served as a self-control, given the absence of an untreated control group.
  • Study Limitations:
    • Small sample size (12 mares) limits generalizability of findings.
    • Lack of a parallel control group restricts the ability to definitively attribute improvements to AMC-EV treatment.
  • Future Directions: Further larger-scale studies with control groups are needed to confirm the therapeutic efficacy and explore mechanisms of AMC-EVs in CDE treatment.

Cite This Article

APA
(2026). Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment. Vet Med Sci, 12(2), e70685. https://doi.org/10.1002/vms3.70685

Publication

Veterinary medicine and science
ISSN: 2053-1095
NlmUniqueID: 101678837
Country: England
Language: English
Volume: 12
Issue: 2
Pages: e70685
PII: e70685

Researcher Affiliations

MeSH Terms

  • Animals
  • Horses
  • Female
  • Horse Diseases / therapy
  • Extracellular Vesicles
  • Endometritis / veterinary
  • Endometritis / therapy
  • Mesenchymal Stem Cells
  • Pregnancy
  • Amnion / cytology
  • Chronic Disease / veterinary

Conflict of Interest Statement

The authors declare no conflicts of interest.

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