Abstract

Simple SummaryDiseases of the endometrium are a frequent cause of subfertility in mares and have an economic impact on the horse breeding industry. These include periglandular fibrosis of endometrial glands (endometrosis), degenerative diseases of vessels (angiosis), inflammation (endometritis), as well as altered differentiation of endometrial glands. Some mares are susceptible towards persistent endometritis. The etiology and pathogenesis of endometrosis are still unclear. This review describes morphological hallmarks and molecular features associated with endometrial health and different types of diseases. The presented literature data reveal characteristic differences in the expression of several extra- and intracellular molecules between the healthy and diseased equine endometrium. Some of these molecules can be detected directly within the tissue and thus have the potential to serve as excellent diagnostic markers for the presence of endometrial diseases. The knowledge of disease-associated changes in cellular differentiation, secretory functions, and immune mechanisms will help to decipher pathogenesis and will contribute to the development of novel treatments. In addition, the quantification of molecular alterations may contribute to a fertility prognosis for an individual mare. Reproductive health increases the well-being of mares and reduces financial loss for the horse breeding industry.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.

Highlights

  • Endometrial diseases of mares are an important cause of subfertility

  • The aim of this review is to provide an overview about endometrial diseases of mares from a pathologist’s perspective with emphasis on morphological hallmarks and associated cellular and molecular mechanisms

  • Equine endometrosis has to be distinguished from endometriosis, a disease that occurs in women and menstruating primates and that is characterized by the implantation of dispersed endometrial tissue within the pelvic or abdominal cavities [63]

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Summary

A Review of Morphological Features and Molecular Analyses

Simple Summary: Diseases of the endometrium are a frequent cause of subfertility in mares and have an economic impact on the horse breeding industry. These include periglandular fibrosis of endometrial glands (endometrosis), degenerative diseases of vessels (angiosis), inflammation (endometritis), as well as altered differentiation of endometrial glands. The presented literature data reveal characteristic differences in the expression of several extra- and intracellular molecules between the healthy and diseased equine endometrium Some of these molecules can be detected directly within the tissue and have the potential to serve as excellent diagnostic markers for the presence of endometrial diseases. Reproductive health increases the well-being of mares and reduces financial loss for the horse breeding industry

Introduction
Endometrial Histology and Influencing Factors
Expression of Estrogen and Progesterone Receptors during the Estrous Cycle
Expression of Glandular Secretory Proteins
Expression of Cytoskeletal Proteins
Resident Immune Cells
Innate Immune Defenses
The Endometrial Biopsy as Diagnostic Tool
Equine Endometrosis
Diagnostic Features of Endometrosis
Molecular Characteristics of Endometrosis
The Pathogenesis of Endometrosis—Still to be Revealed
Endometritis—Subclassification and Disease Susceptibility
Suppurative Endometritis
Nonsuppurative Endometritis
Endometritis Eosinophilica
Granulomatous Endometritis
Cytology as Diagnostic Tool for Endometritis
The Susceptible Mare
Endometrial Maldifferentiation During the Breeding Season
Glandular Inactivity During the Breeding Season
Irregular Glandular Differentiation During the Breeding Season
Unequal Glandular Differentiation During the Breeding Season
Angiopathies
Angiosis—Diagnostic Features
Angiosis—Influence of Age and Parity
Endometrial Cancer: A Rare Disease in Mares
Different Equine Endometrial Diseases: A Common Cause for Subfertility?
Biomarkers for Equine Endometrial Health and Disease
Molecular Research to Improve Treatment
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