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Reproduction in domestic animals = Zuchthygiene2014; 49 Suppl 4; 82-87; doi: 10.1111/rda.12397

Physiopathologic mechanisms involved in mare endometrosis.

Abstract: Endometrosis is a degenerative chronic process, characterized by paramount fibrosis development in mare endometrium. This condition is one of the major causes of subfertility/infertility in mares. As in other organs, fibrosis might be a pathologic sequel of many chronic inflammatory diseases. However, aetiology and physiopathologic mechanisms involved in endometrial fibrosis are still controversial. This review presents new hypotheses based on our newest data. As the first line of innate immune defence, systemic neutrophils arrive in the uterus at mating or in the presence of pathogens. A novel paradigm is that neutrophils cast out their DNA in response to infectious stimuli and form neutrophil extracellular traps (NETs). We have shown that bacterial strains of Streptococcus zooepidemicus, Escherichia coli or Staphylococcus capitis, known to cause endometritis in mares were able to induce NETs release in vitro by equine PMN to different extents. An intriguing dilemma is the dual action of NETs. While NETs play a desirable role fighting micro-organisms in mare uterus, they may also contribute to endometrial fibrosis. A long-term in vitro exposure of mare endometrium explants to NETs components (myeloperoxidase, elastase and cathepsin G) up-regulated fibrosis markers TGFβ and Tissue inhibitor of metalloproteinase (TIMP-1). Also, pro-fibrotic cytokines regulated collagen deposition and fibrosis. Changes in expression of connective tissue growth factor (CTGF), interleukins (IL)1-α, IL-1β, IL-6 and receptors in endometrium with different degrees of fibrosis and/or inflammation were observed. A putative role of CTGF, IL and NETs components in endometrosis development should be considered. Additionally, we speculate that in sustained endometritis in mares, prostaglandins may not only cause early luteolysis or early pregnancy loss, but may also be related to endometrial fibrosis pathogenesis by stimulating collagen deposition.
© 2014 Blackwell Verlag GmbH.
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Publication Date: 2014-10-04 PubMed ID: 25277436DOI: 10.1111/rda.12397Google 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 study investigates the mechanisms leading to endometrosis, a common cause of infertility in mares. It reveals that neutrophils, types of white blood cells, respond to infections by releasing neutrophil extracellular traps (NETs) which not only fight off microbes but may also contribute to the endometrial fibrosis characteristic of endometrosis. The study further explores the role of specific enzymes and cytokines in this process.

Mechanisms of Endometrosis in Mares

This research focuses on understanding the chronic inflammatory process that results in endometrosis in mares. Endometrosis is a condition characterized by excessive fibrous connective tissue proliferation in the endometrium (the inner lining of the uterus) leading to fertility issues.

  • The study brings attention to the systemic neutrophils, which are a part of the immune system, arriving at the uterus in response to mating or presence of pathogens.
  • These neutrophils react to infectious stimuli by spewing out their DNA to form NETs, which are structures that immobilise and eliminate pathogens.
  • However, a key revelation of this study is the possibility of these NETs contributing to endometrial fibrosis, the defining feature of endometrosis, due to their long-term exposure to the endometrium.

The Role of NET components and Cytokines

Diving further into the molecular mechanisms, the study identified various key enzymes and cytokines involved with the formation of these NETs and subsequently, the process of fibrosis:

  • The components of NETs such as myeloperoxidase, elastase, and cathepsin G, when exposed to the endometrium for a prolonged period, up-regulated fibrosis markers like TGFβ and TIMP-1.
  • It was also observed that pro-fibrotic cytokines regulated the deposition of collagen, a key player in fibrosis.
  • Changes in expression of other factors like connective tissue growth factor (CTGF) and specific interleukins (IL) were also noted in endometrium with varying degrees of fibrosis and/or inflammation.
  • The research thus suggests a potential role for CTGF, IL and NETs components in the development of endometrosis in mares.

Prostaglandins and Endometrial Fibrosis

An additional proposition made by the researchers is that prostaglandins, compounds with hormone-like effects, could also be implicated in endometrial fibrosis:

  • In a condition of sustained endometritis (inflammation of the endometrium), prostaglandins not only cause early luteolysis (degradation of the corpus luteum) or early pregnancy loss, but may also augment the pathogenesis of fibrosis by stimulating collagen deposition.

Cite This Article

APA
Rebordão MR, Galvão A, Szóstek A, Amaral A, Mateus L, Skarzynski DJ, Ferreira-Dias G. (2014). Physiopathologic mechanisms involved in mare endometrosis. Reprod Domest Anim, 49 Suppl 4, 82-87. https://doi.org/10.1111/rda.12397

Publication

Reproduction in domestic animals = Zuchthygiene
ISSN: 1439-0531
NlmUniqueID: 9015668
Country: Germany
Language: English
Volume: 49 Suppl 4
Pages: 82-87

Researcher Affiliations

Rebordão, M R
  • C.I.I.S.A., Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Coimbra College of Agriculture, Coimbra, Portugal.
Galvão, A
    Szóstek, A
      Amaral, A
        Mateus, L
          Skarzynski, D J
            Ferreira-Dias, G

              MeSH Terms

              • Animals
              • Cytokines / genetics
              • Cytokines / metabolism
              • Endometriosis / etiology
              • Endometriosis / metabolism
              • Endometriosis / microbiology
              • Endometritis / etiology
              • Endometritis / metabolism
              • Endometritis / microbiology
              • Endometritis / veterinary
              • Endometrium / metabolism
              • Extracellular Traps / physiology
              • Female
              • Fibrosis
              • Horse Diseases / etiology
              • Horse Diseases / metabolism
              • Horse Diseases / microbiology
              • Horses
              • Pregnancy
              • Prostaglandins / metabolism

              Citations

              This article has been cited 22 times.
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