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

Abstract

Mares are seasonally polyestric. The breeding season in spring and summer and the winter anestrus are flanked by transitional periods. Endometrial diseases are a frequent cause of subfertility and have an economic impact on the horse breeding industry. They include different forms of endometrosis, endometritis, glandular maldifferentiation, and angiosis. Except for suppurative endometritis, these are subclinical and can only be diagnosed by the microscopic examination of an endometrial biopsy. Endometrosis is characterized by periglandular fibrosis and nonsuppurative endometritis by stromal infiltration with lymphocytes and plasma cells. The pathogenesis of endometrosis and nonsuppurative endometritis is still undetermined. Some mares are predisposed to persistent endometritis; this has likely a multifactorial etiology. Glandular differentiation has to be interpreted under consideration of the season. The presence of endometrial diseases is associated with alterations in the expression of several intra- and extracellular molecular markers. Some of them may have potential to be used as diagnostic biomarkers for equine endometrial health and disease. The aim of this review is to provide an overview on pathomorphological findings of equine endometrial diseases, to outline data on analyses of cellular and molecular mechanisms, and to discuss the impact of these data on reproduction and treatment.

Equine Endometrosis Pathological Features: Are They Dependent on NF-κB Signaling Pathway?

“…As its occurrence is widespread, endometrosis is an important cause of financial losses in the equine breeding industry. Main paramount features of this disease encompass periglandular fibrosis of the endometrium and degenerative changes of endometrial glands associated with dysfunction of affected glandular epithelial cells [ 1 , 2 ]. Since adequate endometrial gland response is crucial in the nutrition of the embryo, as the severity of endometrosis increases, the risk of embryonic death increases [ 1 , 3 ].…”

“…This classification allocates uterine biopsy samples into categories I, IIA, IIB, and III [ 3 ]. However, more recent studies have assessed the damage of glandular epithelial cells and the metabolic activity of periglandular stromal cells as the basis for the development of an additional endometrosis classification system into four histopathological types [ 1 , 2 , 4 ]. This classification divides uterine biopsy samples using the terms destructive or nondestructive endometrosis for the description of the damaging glands, and active or inactive endometrosis for the characterization of the metabolic activity of the stroma.…”

“…This classification divides uterine biopsy samples using the terms destructive or nondestructive endometrosis for the description of the damaging glands, and active or inactive endometrosis for the characterization of the metabolic activity of the stroma. Following Schöniger and Schoon’s opinion, these two classifications complement each other, and their combination allows for a better description of the affected mare’s endometrium [ 2 ]. It should be kept in mind that the better the description of the current state of the endometrium, the more adequate the assessment of the severity of the endometrial fibrosis, and hence a more accurate prognosis of the future fertility of the mare [ 1 , 2 , 4 ].…”

“…Following Schöniger and Schoon’s opinion, these two classifications complement each other, and their combination allows for a better description of the affected mare’s endometrium [ 2 ]. It should be kept in mind that the better the description of the current state of the endometrium, the more adequate the assessment of the severity of the endometrial fibrosis, and hence a more accurate prognosis of the future fertility of the mare [ 1 , 2 , 4 ].…”

“…Moreover, hyaluronan synthases (HASs) have been suggested as the indicators of the production of ECM components with diverse biological functions [ 13 , 14 , 15 ], as well as monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα) as the proinflammatory molecules involved in the activation of fibrogenesis pathway by acting on cells residing in ECM [ 16 , 17 , 18 , 19 , 20 ]. Given the need to evaluate regular and abnormal cellular function within the mares’ endometria, some of these biomarkers should be considered to have prognostic value for breeding success or for the response to treatment of fibrosis [ 2 , 21 ].…”