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Topic:Endometrium
The equine endometrium is the innermost lining of the uterus in horses, playing a vital role in reproductive health and fertility. It is responsible for providing a suitable environment for embryo development and implantation. The endometrium undergoes cyclical changes during the mare's estrous cycle, influenced by hormonal fluctuations. These changes prepare the uterus for potential pregnancy and are essential for maintaining uterine health. Various conditions, such as endometritis or endometrial fibrosis, can affect the endometrium, impacting reproductive efficiency. This page gathers peer-reviewed research studies and scholarly articles that explore the structure, function, and pathological conditions of the equine endometrium, as well as their implications for equine reproduction.
Review of Pseudomonas aeruginosa and Klebsiella pneumoniae as venereal pathogens in horses. Three bacteria extensively acknowledged as venereal pathogens with the potential to induce endometritis include Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), specific strains of Pseudomonas aeruginosa, and certain capsule types of Klebsiella pneumoniae. The United Kingdom's Horserace Betting Levy Board recommends pre-breeding screening for these bacteria in their International Codes of Practice and >20 000 samples are tested per annum in the United Kingdom alone. While the pathogenesis and regulatory importance of CEM are well established, an evaluat...
Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis. Mare endometrosis is a major reproductive problem associated with low fertility and is characterized by persistent inflammation, TGFβ-1 signaling, and consequently, extracellular matrix deposition, which compromises endometrial glands. Mesenchymal stem cell-based products (MSCs), such as extracellular vesicles (EVs), have gained attention due to the regulatory effects exerted by their miRNA cargo. Here, we evaluated the impact of preconditioning equine adipose mesenchymal stem cells with TGFβ-1 for short or long periods on the anti-fibrotic properties of secreted extracellular vesicles. MSCs...
Evaluating the IL-6 Family of Cytokines Throughout Equine Gestation. The interleukin (IL)-6 family of cytokines is grouped by a common receptor subunit (gp130), but functions in distinct but overlapping physiological activities, including regulation of acute phase reaction and the balance between effector and regulatory T cell populations-both of which play a role in successful pregnancy maturation. Methods: Here, we aim to assess the expression profiles of members of the IL-6 cytokine family throughout equine gestation. To do so, RNA Sequencing was performed on chorioallantois and endometrium of mares at 120, 180, 300, and 330 days of gestation (n = 4/stage), ...
Prostaglandin-related genes are differentially expressed in equine endometrium with different biopsy grade, degrees of inflammation, and fibrosis. Prostaglandins have many roles in the equine reproductive tract, including but not limited to luteolysis, luteal support, ovulation, transport through the uterine tube, uterine contraction, embryonic mobility, inflammation, and fibrosis. Altered secretion of inflammatory proteins are likely to disrupt the balance of endometrial function and could impair fertility. Our overall goal was to measure the expression of several prostaglandin- and inflammation-related genes in mares with different degrees of endometrial histological changes. Our hypothesis was that mares with neutrophilic and lymphocy...
Use of regenerative medicine in the treatment of endometritis in mares: A systematic review and meta-analysis. Defining the optimal therapy for endometritis remains a significant challenge for clinicians. Given the public health threat posed by antibiotic resistance and the inconclusiveness of traditional therapies, regenerative medicine has been proposed as an alternative. The objective of this study was to conduct a comprehensive systematic review and meta-analysis, to investigate the efficacy of regenerative medicine products in the treatment of both post-breeding persistent and chronic degenerative endometritis (PBIE/CDE) in mares, following the PRISMA guidelines. This research could be a comprehen...
In mares resistant to endometrial infection, periovulatory treatment with ecbolic drugs does not influence uterine clearance or luteal development. We aimed to determine associations between experimentally impaired uterine clearance or treatment with ecbolic drugs on luteal development in estrous mares after insemination. In a crossover design, eight mares were treated with saline (CON), clenbuterol (CLEN), oxytocin (OXY) and carbetocin (CARB) from the day of first insemination until 2 days after ovulation. Between treatments, the mares rested for one cycle. Estrous mares were examined for the presence of free intrauterine fluid by transrectal ultrasound. Endometrial swabs for cytology and bacteriology were collected on days 1 and 14. Blo...
Early Embryonic Development in Agriculturally Important Species. The fertilization of oocytes ovulated by pigs, sheep, cows, and horses is not considered a limiting factor in successful establishment of pregnancy. Pig, sheep, and cow embryos undergo cleavage to the blastocyst stage, hatch from the zona pellucida, and undergo central-type implantation. Hatched blastocysts of pigs, sheep, and cows transition from tubular to long filamentous forms to establish surface area for exchange of nutrients and gases with the uterus. The equine blastocyst, surrounded by external membranes, does not elongate but migrates throughout the uterine lumen before attaching to ...
Metagenomic characterization of the equine endometrial microbiome during anestrus. The equine uterus is highly interrogated during estrus prior to breeding and establishing pregnancy. Many studies in mares have been performed during estrus under the influence of high estrogen concentrations, including the equine estrual microbiome. To date, it is unknown how the uterine microbiome of the mare is influenced by cyclicity; while, the equine vaginal microbiome is stable throughout the estrous cycle. We hypothesized that differences would exist between the equine endometrial microbiome of mares in estrus and anestrus. The aim of this study was two-fold: to characterize the reside...
Bacterial endometritis-induced changes in the endometrial proteome in mares: Potential uterine biomarker for bacterial endometritis. Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: ne...
Pregnancy and Luteal Responses to Embryo Reinsertion following Embryo Flushing in Donor Mares. The effect of embryo reinsertion immediately after embryo flushing was studied. In Experiment 1, eight mares were used during 32 cycles (8 cycles in each group). For the first two groups, inseminated mares were flushed 8 days after ovulation and prostaglandin F2α was not administered: in group EF-ET (embryo flushing and embryo transfer) the embryo was reinserted in the same donor mare, while in the EF group, no further procedure was performed. In the third group (ET), non-inseminated mares (recipients) received a Day 8 embryo. Progesterone concentration was measured before EF/ET and 72 h afte...
Effect of duration of estradiol exposure on embryo survival and endometrial gene expression in anestrous embryo recipient mares. Previous studies indicate a positive correlation between the duration of estrus prior to ovulation and likelihood of pregnancy in embryo recipient mares. However, the mechanisms by which the duration of estrus before may affect fertility remains unclear. This study aimed to determine the effect of different durations of estradiol exposure, prior to progesterone administration, on embryo viability in anestrous recipient mares, and endometrial expression of genes thought to influence embryo survival. Three groups of anestrous recipient mares treated with different duration of estradiol were used...
De novo reconstruction of a functional in vivo-like equine endometrium using collagen-based tissue engineering. To better understand molecular aspects of equine endometrial function, there is a need for advanced in vitro culture systems that more closely imitate the intricate 3-dimensional (3D) in vivo endometrial structure than current techniques. However, development of a 3D in vitro model of this complex tissue is challenging. This study aimed to develop an in vitro 3D endometrial tissue (3D-ET) with an epithelial cell phenotype optimized by treatment with a Rho-associated protein kinase (ROCK) inhibitor. Equine endometrial epithelial (eECs) and mesenchymal stromal (eMSCs) cells were isolated separat...
The interaction between seminal plasma, sperm, and endometrium in inter- and intra-species breeding in equids. Anecdotal experience suggests horse mares have less post-breeding inflammation and better fertility when bred with donkeys. This study aimed to compare the post-breeding inflammatory response of mares exposed to donkey and horse semen and seminal plasma and evaluate the proteome and metabolome of donkey and horse sperm and seminal plasma. Uterine edema, intrauterine fluid accumulation, PMNs on cytology, and concentrations of progesterone, and pro- and anti-inflammatory cytokines (IL1, IL1, IL4, IL6, CXCL8, IL10) concentrations were assessed pre-and post-infusion of semen and seminal plas...
Analysis of gene and protein expression in the endometrium for validation of an ex vivo model of the equine uterus using PCR, digital and visual histopathology. In the past, most research in equine reproduction has been performed in vivo but the use of in vitro and ex vivo models has recently increased. This study aimed to evaluate the functional stability of an ex vivo hemoperfused model for equine uteri with molecular characterization of marker genes and their proteins. In addition, the study validated the respective protein expression and the aptness of the software QuPath for identifying and scoring immunohistochemically stained equine endometrium. After collection, uteri (n = 12) were flushed with preservation solution, transported to the labor...
Endometrial expression of antimicrobial peptides as markers of subclinical endometritis in mares. Endometritis is a major cause of subfertility in mares. Multiparous old mares are more susceptible to developing endometritis given that ageing is associated with an altered immune response and with inadequate physiological uterine clearance after breeding, which can lead to degenerative changes in the endometrium. Molecules such as antimicrobial peptides (AMPs) have been proposed as endometritis markers in the equine species. Methods: Cross-sectional. Objective: To investigate the endometrial expression of defensin-beta 4B (DEFB4B), lysozyme (LYZ) and secretory leukocyte peptidase inhibitor (...
Bioinformatic analysis of endometrial miRNA expression profile at day 26-28 of pregnancy in the mare. The establishment of the fetomaternal interface depends on precisely regulated communication between the conceptus and the uterine environment. Recent evidence suggests that microRNAs (miRNAs) may play an important role in embryo-maternal dialogue. This study aimed to determine the expression profile of endometrial miRNAs during days 26-28 of equine pregnancy. Additionally, the study aimed to predict target genes for differentially expressed miRNAs (DEmiRs) and their potential role in embryo attachment, adhesion, and implantation. Using next-generation sequencing, we identified 81 DEmiRs betwe...
Intrauterine devices influence prostaglandin secretion by equine uterus: in vitro and in vivo studies. Intrauterine devices (IUD) are used in the veterinary practice as the non-pharmacological method of oestrus suppression in mares. When placed in the uterus, IUD create a physical contact with the endometrium that mimics the presence of an equine embryo. However, the mechanism of their action has not been fully elucidated. The objective of the present study was to examine the effect of mechanical stimulation of IUD on mare`s endometrium in both in vitro and in vivo study. For this purpose, we demonstrated the effect of IUD on prostaglandin (PG) F and PGE secretion, and mRNA transcription of gen...
Isolation of lactic acid bacteria from the reproductive tract of mares as potentially beneficial strains to prevent equine endometritis. Endometritis, the inflammation of the endometrium, is the leading cause of subfertility in mares, and therefore responsible for major economic losses in the horse industry worldwide. It is generally treated with uterine lavages combined with ecbolic agents and local or systemic antibiotics. However, since antibiotic overuse has been associated with antimicrobial resistance in mares with persistent endometritis, new prevention and treatment alternatives are needed. One such alternative could be the use of probiotic lactic acid bacteria (LAB) isolated from the host. Thanks to their species speci...
Inflammatory markers for differentiation of endometritis in the mare. Endometrial biopsy is required to diagnose mares with chronic endometritis and endometrial degenerative fibrosis. An increase in understanding of equine reproductive immunology could be utilised to create less-invasive, time-efficient diagnostic tools especially when evaluating mares for chronic endometritis. Objective: To evaluate inflammatory cytokine and chemokine concentrations in uterine fluid samples collected by low-volume lavage (LVL) as a potential screening diagnostic biomarker for endometritis. Methods: Prospective cross-sectional clinical study. Methods: Forty-six mares underwent a...
Transcriptomic profiling of mare endometrium at different stages of endometrosis. In the current study, transcriptome profiles of mare endometrium, classified into categories I, IIA, and IIB according to Kenney and Doig, were compared using RNA sequencing, analyzed, and functionally annotated using in silico analysis. In the mild stage (IIA) of endometrosis compared to category I endometrium, differentially expressed genes (DEGs) were annotated to inflammation, abnormal metabolism, wound healing, and quantity of connective tissue. In the moderate stage (IIB) of endometrosis compared to category I endometrium, DEGs were annotated to inflammation, fibrosis, cellular home...
Distribution of degenerative changes in the equine endometrium as observed in a single versus two biopsies. Equine endometrial degeneration is diagnosed by microscopy of an endometrial biopsy but it is uncertain if findings in a single biopsy represent the state of the entire endometrium. Previous studies have compared samples from multiple sites but conclusions are inconsistent. Further clarification is therefore needed. In this study, presence and characteristics of endometrial degeneration were compared in two full thickness specimens from the ventral base of both uterine horns, obtained post mortem from cyclic mares (n = 82). Hematoxylin and eosin-stained sections were blinded evaluated for pe...
MicroRNAs in equine Endometritis: A review of pathophysiology and molecular insights for diagnostic and therapeutic strategies. Endometritis plays an important role in mare infertility. Certain infectious agents interfere with the innate immune system of endometrium, causing a systemic inflammatory response that lasts for a long time and circulates via the blood or cellular degeneration, leading to endometritis due to bacterial endotoxins. Different small, non-coding RNA molecules are involved in many biological functions. For instance, microRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. These miRNAs are important regulators of gene expression, primarily via inhibiting transcripti...
RNA in situ hybridization of Escherichia coli in equine endometrial biopsies. Endometritis is one of the major causes of infertility in mares. and -haemolytic streptococci are among the bacterial species most frequently isolated from the equine uterus. Some bacteria such as -hemolytic streptococci, can persist in dormant forms and cause prolonged, latent or recurrent infections. Dormant bacteria may be present despite negative bacterial cultures, and they are resistant to antimicrobial treatment due to their resting metabolic state. The purpose of this study was to study formalin-fixed paraffin-embedded equine endometrial biopsies for the presence and localization of -...
General and comparative aspects of endometritis in domestic species: A review. Endometritis is a leading cause of sub- and infertility in domestic animal species. The healthy uterus is colonized by commensal bacteria, viruses and yeast/fungi that represent the nonpathogenic microbiota. A shift in the number or type of organisms accompanied by immune dysfunction, however, may trigger uterine infection and inflammation. Metritis is associated with inflammation of all uterine layers (endometrium, myometrium and perimetrium), whereas endometritis is a more superficial inflammation involving solely the endometrium. Endometritis generally occurs at two time points in domestic ...
5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts. Endometrosis negatively affects endometrial function and fertility in mares, due to excessive deposition of type I (COL1) and type III (COL3) collagens. The pro-fibrotic transforming growth factor (TGF-β1) induces myofibroblast differentiation, characterized by α-smooth muscle actin (α-SMA) expression, and collagen synthesis. In humans, fibrosis has been linked to epigenetic mechanisms. To the best of our knowledge, this has not been described in mare endometrium. Therefore, this study aimed to investigate the in vitro epigenetic regulation in TGF-β1-treated mare endometrial fibroblasts an...
Relationship between Clinical Uterine Findings, Therapy, and Fertility in the Mare. Persistent breeding-induced endometritis (PBIE) is a major cause of subfertility in horses and the susceptibility is increased by several factors. The aim of this study was to determine the effects of clinical uterine findings and PBIE therapies, respectively, on pregnancy rate in mares. The analysis included records from 220 mares (390 cycles) inseminated at an artificial insemination (AI) center in Switzerland. Gynecological examinations were performed repeatedly before and after AI to determine cervical tone, uterine edema, and intrauterine fluid accumulation. Pregnancy rate was lower (p 0...
The Effect of Treatment with Oestradiol Benzoate on Oestrus Expression and Endometrial Oedema in Anovulatory and Cyclic Mares. Oestrogens treatment is often used to induce oestrus behaviour in anoestrous mares to aid in the collection of stallion semen and as recipient mares to receive embryos when combined with progesterone. However, there are no studies to describe the effect of dose and individual mare on the intensity and duration of the response, in both anoestrous and cyclic mares. In Experiment 1, 13 anoestrous mares were treated with one of five doses of oestradiol benzoate (OB) (1, 1.5, 2, 3 and 4 mg) per mare in five consecutive treatment periods (n = 65), to determine the response in terms of endometrial oe...
Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium. Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (C...
Characterization of Myeloperoxidase in the Healthy Equine Endometrium. Myeloperoxidase (MPO), as a marker of neutrophil activation, has been associated with equine endometritis. However, in absence of inflammation, MPO is constantly detected in the uterine lumen of estrous mares. The aim of this study was to characterize MPO in the uterus of mares under physiological conditions as a first step to better understand the role of this enzyme in equine reproduction. Total and active MPO concentrations were determined, by ELISA and SIEFED assay, respectively, in low-volume lavages from mares in estrus ( = 26), diestrus ( = 18) and anestrus ( = 8) in absence of endometr...
Safety and Effects of a Commercial Ozone Foam Preparation on Endometrial Environment and Fertility of Mares. Mares' subfertility represents a complex diagnostic and therapeutic challenge and both clinical and subclinical endometritis are considered major causes of impaired fertility. Thanks to its properties, ozone has a big potential as a treatment for equine endometritis. Therefore, the aim of this study is to describe the safety and the effects on endometrium and reproductive parameters of mares of a commercial ozone foam preparation (Riger Spray®). Twenty-four mares were treated during estrus: ozone group with an intrauterine instillation of ozone foam preparation (OG, n=16) and control group wi...
