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Equine veterinary journal2024; doi: 10.1111/evj.14058

Inflammatory markers for differentiation of endometritis in the mare.

Abstract: Endometrial biopsy is required to diagnose mares with chronic endometritis and endometrial degenerative fibrosis. An increase in understanding of equine reproductive immunology could be utilised to create less-invasive, time-efficient diagnostic tools especially when evaluating mares for chronic endometritis. Objective: To evaluate inflammatory cytokine and chemokine concentrations in uterine fluid samples collected by low-volume lavage (LVL) as a potential screening diagnostic biomarker for endometritis. Methods: Prospective cross-sectional clinical study. Methods: Forty-six mares underwent a LVL and subsequently endometrial biopsy. Mares were split in three groups: healthy, acute endometritis, and chronic endometrial fibrosis (CEF) based on cytological and histological evaluation. A fluorescent bead-based multiplex assay for IFN-γ, IFN-α, IL-1β, IL-4, IL-10, IL-17, sCD14, TNF-α, CCL2, CCL3, CCL5 and CCL11 were carried out on the LVL fluid. The endometrial biopsy was utilised for histology and qPCR of IFN-γ, IL-1β, IL-6, IL-8, IL-17, TNF-α, CCL2 and CCL3 genes. Statistical analyses examined differences in inflammatory markers and predictive modelling for diseased endometrium. Results: Secreted concentrations of IFN-γ were lower in LVL fluid from reproductively healthy mares compared with acute endometritis (p = 0.04) and CEF (p = 0.006). Additionally, IL-17, IL-10, IL-1β, TNF-α, CCL2, CCL3, CCL5 and CCL11 were significantly increased (p ≤ 0.04) in LVL from CEF mares compared with healthy mares. Mares with CCL2 concentrations ≥550 pg/mL (14/14) had 100% probability of having CEF and/or acute endometritis. Healthy mares had lower relative abundance of IL-17 mRNA compared with mares in CEF group [median (interquartile rage) = 14.76 (13.3, 15.3) and 12.4 (10.54, 13.81)], respectively (p = 0.02). Conclusions: Limited sample size: larger numbers of mares with and without endometritis are required and reference intervals in LVL samples have to be established. Conclusions: Inflammatory chemokines and cytokines concentrations differed between healthy mares and mares with acute endometritis or CEF in LVL.
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Publication Date: 2024-01-14 PubMed ID: 38219734DOI: 10.1111/evj.14058Google 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.

This research investigates the use of inflammatory markers in mare uterine fluid to differentiate types of endometritis, a common issue in equine reproduction. The researchers hope that a better understanding of these markers will help develop quicker and less invasive diagnostic tools for chronic endometritis, using fluid sampling rather than traditional endometrial biopsy.

Methodology

  • The study is a prospective cross-sectional clinical research, featuring 46 mares that were categorised into three groups based on cytological and histological evaluation: healthy, acute endometritis, and chronic endometrial fibrosis (CEF).
  • Uterine fluid samples were collected from each mare via low-volume lavage (LVL), a less invasive yet effective fluid retrieval method.
  • These samples were then evaluated for the concentrations of certain inflammatory cytokines and chemokines, including IFN-γ, IFN-α, IL-1β, IL-4, IL-10, IL-17, sCD14, TNF-α, and four variations of CCL.
  • The study also involved an endometrial biopsy, where the tissue samples were tested for the presence of certain genes using qPCR.
  • Statistical analyses were used to identify differences in inflammatory markers and predict models for disease detection.

Findings

  • The results showed a lower concentration of IFN-γ in the LVL fluid from reproductively healthy mares compared to those with acute endometritis and CEF.
  • Similarly, concentrations of several inflammatory markers, including IL-17, IL-10, IL-1β, TNF-α, and certain CCLs, were significantly higher in LVL fluid from mares with CEF compared to healthy mares.
  • In the case of mares having CCL2 concentrations greater than or equal to 550 pg/mL, the study found a 100% probability of them having CEF and/or acute endometritis.
  • The relative mRNA abundance of IL-17 was lower in healthy mares as compared to those in the CEF group.

Conclusions

  • This study, though limited by a small sample size, prompts the need for larger studies in order to establish the reference intervals in LVL samples.
  • The results indicate that differences in the concentrations of inflammatory cytokines and chemokines exist between healthy mares and those with acute endometritis or CEF when examined via LVL.
  • This possibly suggests that these biomarkers could potentially be used to detect these conditions in mares, providing a less invasive diagnostic tool than endometrial biopsy.

Cite This Article

APA
Lection J, Wagner B, Byron M, Miller A, Rollins A, Chenier T, Cheong SH, Diel de Amorim M. (2024). Inflammatory markers for differentiation of endometritis in the mare. Equine Vet J. https://doi.org/10.1111/evj.14058

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Lection, Jennine
  • Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, New York, USA.
Byron, Michael
  • Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
Miller, Andrew
  • Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA.
Rollins, Alicia
  • Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, New York, USA.
Chenier, Tracey
  • Department of Population Medicine, University of Guelph, Guelph, Ontario, Canada.
Cheong, Soon Hon
  • Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
Diel de Amorim, Mariana
  • Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.

Grant Funding

  • 2019-67015-29833 / USDA/NIFA Development of Equine Immune Reagents
  • Harry M. Zweig Memorial Fund for Equine Research University

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Citations

This article has been cited 3 times.
  1. Ramsaran LN, Byron M, Parry S, Lection J, Back B, Grenier J, Cheong SH, Diel de Amorim M. Investigation of gene stability in equine luteal tissue during mid-diestrus phase and early pregnancy - Research Article. BMC Vet Res 2026 Jan 9;22(1):84.
    doi: 10.1186/s12917-025-05241-6pubmed: 41507934google scholar: lookup
  2. Sadowska A, Molcan T, Słyszewska M, Skarzynski DJ, Ferreira-Dias G, Szóstek-Mioduchowska A. Transcriptomic Insights into Tumor Necrosis Factor α's Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts. Int J Mol Sci 2025 Nov 24;26(23).
    doi: 10.3390/ijms262311344pubmed: 41373504google scholar: lookup
  3. Nash DM, Giles JL. Uterine inflammation and lessons from large animal models of endometritis. Nat Rev Immunol 2025 Dec;25(12):934-946.
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