Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares

Abstract

In this paper, the evolution of our understanding about post breeding endometritis (PBE), the susceptibility of mares, and events leading to endometrosis are reviewed. When sperm arrive in the uterus, pro-inflammatory cytokines and chemokines are released. They attract neutrophils and induce modulatory cytokines which control inflammation. In susceptible mares, this physiological defense can be prolonged since the pattern of cytokine release differs from that of resistant mares being delayed and weaker for anti-inflammatory cytokines. Delayed uterine clearance due to conformational defects, deficient myometrial contractions, and failure of the cervix to relax is detected by intrauterine fluid accumulation and is an important reason for susceptibility to endometritis. Multiparous aged mares are more likely to be susceptible. Untreated prolonged PBE can lead to bacterial or fungal endometritis called persistent or chronic endometritis. Exuberant or prolonged neutrophilia and cytokine release can have deleterious and permanent effects in inducing endometrosis. Interactions of neutrophils, cytokines, and prostaglandins in the formation of collagen and extracellular matrix in the pathogenesis of fibrosis are discussed. Endometritis and endometrosis are interconnected, influencing each other. It is suggested that they represent epigenetic changes induced by age and hostile uterine environment.

Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction

“…As the histopathological type of endometrosis depicted a larger modification of ECM, especially the increase in proteoglycans, fibronectin, and laminin expression [13,15], we have suggested the active remodeling of ECM in FLP. With the evolution of the concepts of equine endometrosis, it was shown that the ECM architecture and endometrial function are affected by the neutrophil extracellular traps (NETs), pro-inflammatory cytokines, pro-fibrotic pathways, growth factors and epigenetics [12].…”

“…Previous studies on the equine endometrium have focused on the molecular mechanisms involved in physiological aspects [1][2][3][4] and the pathogenesis of endometrial diseases, often associated with mares' subfertility [5][6][7][8][9]. Despite the relentless efforts and new scientific reports, the pathogenesis of nonsuppurative endometritis and endometrosis remains unknown, and routinely available treatment is still undeveloped [3,[10][11][12]. Endometrosis, also referred to as degenerative endometrial fibrosis, is the most important clinically silent endometrial disease associated with infertility in mares [13,14].…”

Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction?

“…Two recent studies using multivariable analysis showed an increased risk of EPL with the presence of cysts (Miyakoshi et al 2012;de Mestre et al 2019) even after maternal age and status had been accounted for in the models. It remains unclear whether the cysts themselves cause EPL and/or rather indicate underlying endometrial pathologies that could cumulate in EPL as reviewed here (Katila and Ferreira-Dias 2022). Mares can be bred on their foal heat, however, there are concerns that this practice may lead to an increased incidence of EPL.…”

Relationship between Oxidative Stress and Endometritis: Exploiting Knowledge Gained in Mares and Cows

“…In addition to infections, the immune system plays a pivotal role in this pathology in both species. By intervening in defense of the endometrium, the immune cells release pro-inflammatory cytokines and chemokines, which can themselves become a part of the inflammatory process, creating self-aggravating conditions [ 110 ]. It is currently unknown why endometritis affects some individuals rather than others.…”