Physiopathologic Mechanisms Involved in Mare Endometrosis

Abstract

Contents 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.

Strain-specific induction of endometrial periglandular fibrosis in mice exposed during adulthood to the endocrine disrupting chemical bisphenol A

“…One difference between equine endometrosis and the pathology observed in the C57Bl/6N and CD-1 strains was a lack of MMP2 localization to the glandular and luminal epithelial cells in the mouse endometrium. Also similar to equine endometrosis [105], an increased immune response associated with gland nests was observed, which may have a role in the development of the phenotype. In equine endometrosis, the periglandular stromal cells can differentiate into myofibroblasts that express α-SMA [106].…”

Equine Infectious Endometritis—Clinical and Subclinical Cases

“…Other studies have also shown a relation between poor endometrial quality and susceptibility to infectious endometritis [29][30][31][32]. The underlying mechanism for this relation is not known, but an interaction among chronic bacterial infection, inflammatory mediators, and increased endometrial fibrosis has been suggested [33]. The development of endometrial edema during estrus has been demonstrated to be associated with the circulatory ovarian hormone levels [34].…”

The Healthy and Diseased Equine Endometrium: A Review of Morphological Features and Molecular Analyses

“…In recent years, a major research focus in equine endometrial pathology was to reveal disease-associated cellular and molecular mechanisms [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This will help to gain further insights into the pathogenesis of endometrial diseases [15][16][17][18][19][20][21][22][23][24][25][26][27][28], and it may contribute to the development of effective prophylactic regimes and novel treatment options. Some of the identified biological parameters have the potential to be used as biomarkers for endometrial health and disease.…”