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.
Del Prete C, Gaspari G, Kosior MA, Merlo B, Iacono E, Longobardi C, Martino NA, Dell'Aquila ME, Damiano S, Cocchia N, Gasparrini B, Lange-Consiglio A.Over the years, regenerative therapies have emerged as promising alternatives for persistent breeding-induced endometritis. In vitro studies testing the effects of these therapies on equine endometrial cells are still scarce. This study aimed to evaluate in vitro the effect of Wharton's jelly (WJ) mesenchymal stromal/stem cell (MSCs)-derived conditioned medium (WJ-CM) and platelet-rich plasma (PRP) on equine endometrial cells, with or without lipopolysaccharide (LPS)-induced inflammation. The WJ-CM was obtained after 24 h of starvation in Ringer's lactate of WJ-MSCs and PRP was prepared using...
Gaspari G, Lange-Consiglio A, Cremonesi F, Desantis S.Extracellular vesicles (EVs) are important mediators of cell-cell communication thanks to their ability to transfer their bioactive cargo, thus regulating a variety of physiological contexts. EVs derived from amniotic mesenchymal/stromal cells (eAMC-EVs) are internalized by equine endometrial cells (eECs) with positive effects on regenerative medicine treatments. As the cellular uptake of EVs is influenced by the glycan profile of both EVs and target cells, this study is focused on the role of surface glycans in the uptake of eAMC-EVs by recipient eECs. Equine ECs were obtained by enzymatic di...
Asif S, Gulzar MW.Endometritis is a significant cause of infertility in mare. Some infectious agents disrupt the endometrium's innate immune system, resulting in a prolonged systemic inflammatory response that circulates via the blood or cellular degeneration, which ultimately leads to endometritis from bacterial endotoxins. Numerous biological processes use various small, non-coding RNA molecules called MicroRNAs. MicroRNAs (miRNAs) regulate gene expression after transcription by blocking transcription and translation. This manuscript examines patho-morphological discoveries in equine endometritis, the express...
Ulaangerel T, Mu S, Sodyelalt J, Yi M, Zhao B, Hao A, Wen X, Han B, Bou G.The success or failure of embryo fixation is crucial for embryo attachment and later development. As an epithelial chorioallantoic placenta-type animal, the horse has a special process of embryo implantation, and the mechanism of embryo fixation in horses is still unclear. Methods: In this study, the structural and transcriptomic characteristics of endometrial tissue from the fixed and nonfixed sides of 20-day gestation embryos in Mongolian horses were investigated to search for important genes and potential molecular markers associated with the fixation phase of equine embryos. Results: A com...
Drzewiecka EM, Molcan T, Sadowska A, Piotrowska-Tomala K, Słyszewska M, Dias GF, Skarżyński DJ, Szóstek-Mioduchowska A.Mares with endometrosis exhibit histological changes not only in the endometrium but also in the myometrium that suggest possible functional impairment. The molecular background of these changes is not well understood. We hypothesize that the transcriptomic profile of the mare myometrium varies depending on the degree of endometrosis in mares. Myometria were collected from mares in the mid-luteal phase of the estrous cycle with endometrium categories I, IIA, IIB, and III (∑n = 23), according to Kenney and Doig´s histopathological classification. Myometrial RNA was isolated and subjected...
Jaworska J, Tobolski D, Salem SE, Kahler A, Wocławek-Potocka I, Mestre AM.Embryo implantation in the mare occurs just over one month after fertilization, coinciding with the production of chorionic gonadotropin. The factors that regulate this late implantation in the mare, and whether they are unique to horses or shared with more invasive embryo implantation in other species, remain poorly understood. This study aimed to determine and compare the transcriptome and subpopulations of endometrial cells before and after embryo implantation in the horse. Single-cell RNA sequencing was used to characterize the transcriptome of nearly 97,000 endometrial cells collected fro...
Bernabe MCM, Fonseca BB, Silva MVC, Pedrosa IE, Silva MB, Sommerfeld S, de Sousa ALP, de Leva Resende BC, Sousa ACP, Dos Santos Freitas A....Endometritis is one of the main reproductive disorders in mares and due to the increasing prevalence of antibiotic resistance, the use of probiotics in the prevention and treatment of endometritis in mares has gained interest, given their potential to restore and maintain a healthy uterine microbiota. Therefore, the aim of this study was to evaluate the antimicrobial properties of total metabolites of Lactobacillus acidophilus (LA) and Lactiplantibacillus plantarum (LP) against common equine endometrial pathogenic bacteria in vitro (Acinetobacter baumannii, Escherichia coli (1), Escherichia co...
Piotrowska-Tomala KK, Szóstek-Mioduchowska A, Jonczyk AW, Drzewiecka EM, Wrobel MH, Hojo T, Ferreira-Dias G, Skarzynski DJ.Endometrosis (chronic degenerative endometritis) results in morphological changes in the equine endometrium and impairs its secretory function. However, the effect of this condition on the myometrium remains unclear. Lysophosphatidic acid (LPA) may affect female reproductive function and embryo transport by influencing uterine contractility through its receptors (LPARs). The objective of this study was to determine myometrial LPAR1-6 mRNA transcription, and the effects of LPA on myometrial contractions in mares with endometrosis during the mid-luteal and follicular phases of the estrous cycle....
Teixeira-Soares CM, Viana AG, Carvalho RPR, Barros E, Ramirez-Lopez C, Moura AA, Machado-Neves M.Endometritis is the leading cause of subfertility in mares and a significant challenge to equine reproduction. Unraveling uterine fluid proteome may promote advancements in the knowledge of endometritis etiopathogeneses and its diagnosis and therapeutic practices. Therefore, we aimed to characterize and compare the protein profile of the uterine fluid from healthy mares and animals diagnosed with endometritis. Mangalarga Marchador breed mares from Muriaé - Brazil were divided into control, infectious endometritis, and post-breeding endometritis groups (n = 8/ group). Uterine fluid was collect...
Silva BCE, Drzewiecka EM, Piotrowska-Tomala K, Alpoim-Moreira J, Sadowska A, Kowalik MK, Pimenta J, Rebordão MR, Ferreira-Dias G, Skarzynski D....A reduction in myometrial contractile activity can lead to inadequate cleaning of the uterine lumen, resulting in persistent endometritis and potentially endometrosis in mares. Oxytocin (OXT) is a key hormonal regulator of myometrial contraction. While epigenetic regulation of myometrial gene expression has been studied in humans, there is limited information on the expression of DNA methyltransferases (DNMTs) and ten-eleven translocation enzymes (TETs) in the myometrium of mares. This study aimed to evaluate the mRNA transcription of these enzymes and the potential role of DNA methylation in ...
Cerveira-Pinto M, Wójtowicz A, Pires MA, Kordowitzki P, Skarzynski D, Ferreira-Dias G, Szóstek-Mioduchowska A, Amaral A.Increased synthesis and deposition of collagen (COL) in the extracellular matrix (ECM) of equine endometrium contributes to endometrosis. Toll-like receptors (TLRs) are transmembrane receptors involved in the innate immune response, recognized for their role in antigen recognition and previously associated with equine endometritis. The TLRs not only recognize pathogen-associated molecular patterns but also regulate inflammations, fibrosis and cancer. The aim of this study was to explore the relationship between TLR expression at different stages of Kenney and Doig's (K-D) grading and COL1 exp...
Martínez-Bartolomé I, Masot J, Serres C.Kenney-Doig scale is considered the international standard method for classifying uterine biopsies in mares; however, its objectivity has been questioned by various studies. In the present study, we analysed the degree of agreement between two pathologists when assessing the same set of 201 uterine biopsies, obtaining a slight to moderate level of agreement (κ = .34/κ = .57). Subsequently, we developed a numerical scale based on the evaluation of histological parameters, including inflammation, fibrosis, glandular density and lymphatic lacunae. Partial scores were summed to obtain a ...
Derbala MK, Abu-Seida AM, El-Metwally AE, Asfour HAE.Embryo transfer (ET) is regarded as one of the reproductive methods for genetic improvement initiatives in the horse business. The current study aimed to increase the success rate of ET by re-flushing and re-transferring of embryos from contaminated recipient mares into second healthy recipients. The study involved 25 recipient mares that demonstrated embryonic vesicles inside intraluminal fluid (ILF) on ultrasound scanning 2 ± 0.5 days after ET. Seven recipient mares were left without re-flushing and re-transferring of embryos (control group) and 18 recipient mares (treated group) were subje...
Botelho JHV, Pessoa GO, Caixeta ES, Sales G, de Oliveira KR, Nascimento Neto JDP, Ferreira RD, Palhão MP.This study aimed to evaluate the localised effects of intrauterine ozone therapy on endometrial recovery in mares with endometritis. Our investigation assessed changes in gene expression profiles of anti-inflammatory (IL-1RA and IL-10), proinflammatory (IL-R1B3i and TNFα) and pleiotropic (IL-6) cytokines, along with detailed histological measurements of epithelial and endometrial thickness and the glandular area ratio. Twenty mares were assigned to a 2 × 2 factorial design based on endometritis diagnosis and treatment (control or 42 μg/mL ozone insufflation), resulting in four groups: N...
Fedorka CE, El-Sheikh-Ali H, Scoggin KE, Coleman S, Humphrey EA, Troutt L, Troedsson MHT.The establishment of pregnancy involves a fine-tuned balance between protection and tolerance within the maternal immune system, as the female needs to accept a foreign antigen (the semi-allogenic fetus) while still being able to combat pathogens from the uterus. In the horse, the first uterine exposure to paternal antigens is during mating when sperm is introduced to the tissue and draining lymphatics of the uterus. Additionally, it has been suggested that seminal plasma and its proteins within it play an essential role in preparing the female tract for a suitable immunologic environment but ...
Centeno LAM, Bastos HBA, Bueno VLC, Trentin JM, Fiorenza M, Panziera W, Winter GHZ, Kretzmann NA, Fiala-Rechsteiner S, Mattos RC, Rubin MIB.Equine endometrosis is a degenerative and predominantly fibrotic condition resulting from progressive and irreversible multifactorial causes that influence the endometrium of mare. Tissue remodeling in the equine endometrium occurs as part of the pathogenesis of endometrosis, a process characterized by a shift in extracellular matrix (ECM) components. The relationship between matrix metalloproteinases and their specific inhibitors is crucial for the remodeling process. Collagen play a significant role in maintaining a healthy uterus and may promote fibrotic processes. The aim of this study was...
Ricard RM, Wobeser B. is a reported cause of infertility and endometritis in sheep, cattle, and pigs; however, the association between uterine disease and is poorly understood in horses. Recently, a high prevalence of in equine aborted chorioallantoises was reported in horses in western Canada. Based on this high prevalence, investigation into the effects of on infertility and endometritis in western Canadian mares is prudent. We examined 98 formalin-fixed, paraffin-embedded endometrial biopsies from western Canada submitted between 2014 and 2022 using a -specific 16S rRNA PCR test; 40 samples tested positive f...
Gallacher K, Woolford L, Santos LC, Serpa PBS, Len J, Gilbert RO, Kind KL.Endometrial health is vital for the reproductive efficiency of broodmares and accurate diagnostic testing is crucial for directing the best treatment options and outcomes. Confocal laser endomicroscopy (CLE) is an endoscopic technique for obtaining in-vivo, real-time microscopic imaging of tissues using a fiber optic probe. CLE relies on induced tissue fluorescence and fluorescein sodium, given intravenously, is the contrast agent most used in human medicine. This study aimed to determine the feasibility of CLE for imaging equine endometrium and determine a standard dose of fluorescein sodium ...
Scholtz M, Guthrie AJ, Newton R, Schulman ML.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 evaluation...
Wong YS, Mançanares AC, Navarrete F, Poblete P, Mendez-Pérez L, Cabezas J, Riadi G, Rodríguez-Alvarez L, Castro FO.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...
Fedorka CE, Scoggin KE, El-Sheikh Ali H, Troedsson MHT.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), ...
Byron M, Lection J, Foster RA, Chenier T, Wagner B, Diel de Amorim M.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...
Del Prete C, Montano C, Cocchia N, de Chiara M, Gasparrini B, Pasolini MP.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...
Khan Y, El-Shalofy A, Kaps M, Gautier C, Aurich C.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...
Bazer FW, Johnson GA.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 ...
Heil BA, van Heule M, Thompson SK, Kearns TA, Beckers KF, Oberhaus EL, King G, Daels P, Dini P, Sones JL.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...
Da Silva E, Martín-Cano FE, Gómez-Arrones V, Gaitskell-Phillips G, Alonso JM, Rey J, Becerro L, Gil MC, Peña FJ, Ortega-Ferrusola C.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...
Martínez-Boví R, Gaber JTH, Sala-Ayala L, Plaza-Dávila M, Cuervo-Arango J.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...
Sant'Anna Monteiro da Silva E, Sanches Oquendo Júnior P, Gaspari Oquendo FM, Stout TAE, de Ruijter-Villani M, Rodrigues TS, Beletti ME....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...
Santiviparat S, Swangchan-Uthai T, Stout TAE, Buranapraditkun S, Setthawong P, Taephatthanasagon T, Rodprasert W, Sawangmake C, Tharasanit T.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...
Cabezas J, Rojas D, Navarrete F, Ortiz R, Rivera G, Saravia F, Rodriguez-Alvarez L, Castro FO.Adult stromal mesenchymal stem cells (MSCs) have been postulated as responsible for cell renewal in highly and continuously regenerative tissues such as the endometrium. MSCs have been identified in the endometrium of many species including humans, rodents, pets and some farm animals, but not in horses. The objective of this work was to isolate such cells from the endometrium of mares and to compare their main biological attributes with horse adipose-derived MSCs. Here we successfully isolated and characterized endometrial MSCs (eMSCs) from mares. Said cells showed fibroblast-like morphology, ...
Rebordão MR, Galvão A, Szóstek A, Amaral A, Mateus L, Skarzynski DJ, Ferreira-Dias G.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 nove...
Bauersachs S, Wolf E.Different reproductive strategies evolved in various mammalian groups to achieve recognition, establishment and maintenance of pregnancy. The complexity of these processes is reflected by a high incidence of embryonic loss during this critical period in many mammalian species. Besides studies in mice and humans a number of transcriptome studies of endometrial tissue samples and also of early embryos have been performed during the pre-implantation phase in cattle, swine and horse to identify genes associated with embryo-maternal interaction. Results of these studies are reviewed and compared be...
Allen WR, Wilsher S.Constant, self induced mobility throughout the uterine lumen between days 6 and 17 after ovulation, complete envelopment by a self-secreted glycoprotein capsule between days 7 and 30 and 'injection' of specialised, gonadotrophin-secreting trophoblast cells into the maternal endometrium at days 35-37 are three unusual aspects of equine embryogenesis. The outer trophoblast layer of the allantochorion finally establishes a stable, microvillous contact with the lumenal epithelium of the endometrium around days 40-42 and placentation commences thereafter. The allantochorion elongates steadily until...
Stout TA, Allen WR.Between at least day 9 and day 16 after ovulation the spherical equine conceptus migrates continuously throughout the uterine lumen, propelled by peristaltic myometrial contractions. This unusually long period of intrauterine movement ensures that the conceptus delivers its anti-luteolytic signal to the entire endometrium to achieve luteostasis. The present experiment tested the hypothesis that prostaglandins stimulate the myometrial contractions that result in the migration of the conceptus. Serial ultrasonographic examinations of the uteri of eight mares performed during 2 h periods between ...
Lehmann J, Ellenberger C, Hoffmann C, Bazer FW, Klug J, Allen WR, Sieme H, Schoon HA.The aim of the present study was to characterize the morpho-functional features of endometrosis in barren and foaling mares, using both conventional histopathological and immunohistochemical methods. Endometrial biopsy samples were collected during the physiological breeding season from 159 estrous, clinically healthy mares (mean age 12 years), and the quality and degree of endometrosis was histomorphologically defined. The mares were bred and those that foaled were put in the foaling group whereas those that did not foal were placed in the barren group. Foaling mares were then compared with b...
Klein C.Maintenance of pregnancy is dependent on the exchange of signals between the conceptus and the endometrium. The objective of this study was to use next-generation sequencing to determine transcriptome blueprints of the conceptus and endometrium 16 days after ovulation in the horse. There were 7760 and 10 182 genes expressed in the conceptus and endometrium, respectively, of which 7029 were present in both. Genes related to developmental processes were enriched among conceptus-specific transcripts, whereas many endometrium-specific genes had known roles in cell communication, cell adhesion and ...
Szóstek-Mioduchowska AZ, Baclawska A, Okuda K, Skarzynski DJ.Equine endometrosis (endometrial fibrosis) is a degenerative chronic process that occurs in the uterus of the mare and disturbs proper endometrial function. Fibrosis is attributed to excessive deposition of extracellular matrix (ECM) components. The turnover of ECM is mediated by matrix metallopeptidases (MMP). Previously, it was shown that cytokines modulate MMP expression in other tissues and may regulate fibrosis indirectly by attracting inflammatory cells to the site of inflammation and directly on various tissues. However, the regulation of MMP expression in equine endometrosis is still r...
Hurtgen JP.Inflammatory conditions of the uterus, collectively known as endometritis, can be classified as acute, chronic, active, or subclinical. This condition causes substantial reductions in mare fertility. To diagnose and treat mares with endometrial inflammation, it is imperative to identify predisposing factors and challenges to the reproductive tract of the mare in a chronological order; these factors change from those of the young maiden filly to the older, multiparous broodmare. This paper addresses predisposing factors, diagnostic procedures and therapy strategies for different mare groups.
Stout TA, Allen WR.A growing equine conceptus must suppress the cyclical release of PGF(2 alpha) from the endometrium to effect maternal recognition of its presence in the uterus. Paradoxically, the conceptus itself secretes PGF(2 alpha), together with other prostaglandins. In this study, the PGF(2 alpha) and PGE(2) content of, and production in vitro by, day 10-32 equine conceptuses were measured and the influence of pregnancy on the concentrations of these prostaglandins in the uterine lumen was examined. In vitro, the release of both prostaglandins per mg conceptus tissue was very high on day 10 after ovulati...
Fumuso E, Giguère S, Wade J, Rogan D, Videla-Dorna I, Bowden RA.Endometrial mRNA expression of the pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) was assessed in mares resistant (RM) or susceptible (SM) to persistent post-breeding endometritis (PPBE). Eight RM and eight SM, were selected based on reproductive records and functional tests out of a herd of 2,000 light cross-type mares. Three experiments were done to study transcription patterns in (i) basal conditions; (ii) after artificial insemination (AI); and (iii) after administration of an immunomodulator at time of artificial ...
Woodward EM, Christoffersen M, Campos J, Squires EL, Troedsson MH.The objectives were to: (1) investigate the associations of age and endometrial biopsy score with uterine fluid retention after insemination; and (2) determine if a strict classification of susceptibility to persistent breeding-induced endometritis (PBIE) based on biopsy score, endometrial cytology, and fluid retention after inseminations, is consistent over subsequent breeding seasons. In Experiment 1, 57 mares were inseminated with 10(9) freeze-killed sperm during estrus and evaluated for uterine fluid retention 48 h and 96 h after insemination. Comparisons were made between fluid retention ...
Mambelli LI, Winter GH, Kerkis A, Malschitzky E, Mattos RC, Kerkis I.Mesenchymal stem cells (MSCs), because of their immunomodulation and trophic activities, in addition to their capacity to regenerate damaged tissues, have potential for treatment of many diseases. The success of stem cell therapies depends, in part, on the method of cell delivery, which should provide wide cell distribution and homing in to injured sites. The objective of the present study was to developing a novel strategy for delivery of MSCs into the uterus of mares with endometrosis (degenerative alteration of uterine glands and surrounding stroma). Endometrosis was confirmed in all mares ...
Szóstek-Mioduchowska AZ, Baclawska A, Rebordão MR, Ferreira-Dias G, Skarzynski DJ.An increasing number of studies have shown that prostaglandins (PGs) exert multiple regulatory actions in the processes associated to tissue remodeling and fibrosis. Extracellular matrix (ECM) turnover is mediated by matrix metallopeptidases (MMPs). The knowledge about the regulation of their expression in mare endometrium is still limited. Thus, the aim of this study was to investigate whether: (i) profibrotic transforming growth factor (TGF)-β1 modulates PG production in equine endometrium; and (ii) PGE and PGF modulate MMPs, their tissue inhibitors (TIMPs), and collagen 1 (COL1) expression...
Allen WR.Four separate components combine to produce the progesterone and biologically active 5 alpha-reduced pregnanes needed to maintain pregnancy in the mare. The primary corpus luteum (CL) is prolonged beyond its cyclical lifespan by the down-regulation of endometrial oxytocin receptors to prevent activation of the luteolytic pathway and its waning progesterone production is supplemented from day 40 of gestation by the formation of a series of accessory CL which develop in the maternal ovaries as a result of the gonadotrophic actions of pituitary FSH and the equine chorionic gonadotrophin (eCG). Fr...
Corradetti B, Correani A, Romaldini A, Marini MG, Bizzaro D, Perrini C, Cremonesi F, Lange-Consiglio A.Amniotic membrane-derived mesenchymal cells (AMCs) are considered suitable candidates for a variety of cell-based applications. In view of cell therapy application in uterine pathologies, we studied AMCs in comparison to cells isolated from the endometrium of mares at diestrus (EDCs) being the endometrium during diestrus and early pregnancy similar from a hormonal standpoint. In particular, we demonstrated that amnion tissue fragments (AM) shares the same transcriptional profile with endometrial tissue fragments (ED), expressing genes involved in early pregnancy (AbdB-like Hoxa genes), pre-imp...
Ricketts SW, Alonso S.The results of a retrospective analysis of 3,804 endometrial biopsy specimens collected from non-pregnant mares during the course of routine equine stud farm practice demonstrates a significant and practically useful correlation between the severity of chronic degenerative endometrial disease (CDE) diagnosed and age of mare at the time of examination. There were significant correlations between the number of foals born and the mares' barren years prior to biopsy and the severity of CDE, but the differences were not sufficiently large to be useful. Correlations between the severity of chronic i...
Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G.Prostaglandin E (PGE) has contradictory effects in many organs. It may have proinflammatory, anti-inflammatory, or anti-fibrotic roles, depending on the type of receptors to which it binds. By signaling through its receptors EP2 and EP4, PGE mediates anti-inflammatory and anti-fibrotic actions. In spite of chronic endometrial fibrosis (endometrosis) being a major cause of mare infertility, its pathogenesis is not fully understood. We have shown that contact of mare endometrium in vitro with neutrophil extracellular traps (NETs) proteases favors endometrial collagen type I production. Therefor...
Pascottini OB, Aurich C, England G, Grahofer A.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 ...
Boerboom D, Brown KA, Vaillancourt D, Poitras P, Goff AK, Watanabe K, Doré M, Sirois J.Luteolysis in domestic species is mediated by the release of luteolytic pulses of prostaglandin (PG) F(2alpha) by the uterus at the end of diestrus, which must be suppressed by the conceptus to permit maternal recognition of pregnancy. In many species, including the horse, both the conceptus and the endometrium also synthesize PGE(2), which may antagonize PGF(2alpha) by playing a luteotropic and/or antiluteolytic role. While the release of PGE(2) and PGF(2alpha) by the equine endometrium in late diestrus and early pregnancy has been previously studied, the underlying prostaglandin synthase gen...
Hartt LS, Carling SJ, Joyce MM, Johnson GA, Vanderwall DK, Ott TL.Uterine function is primarily controlled by the combined actions of oestrogen and progesterone working through their cognate nuclear receptors. The mechanism of establishment of pregnancy in the mare is of interest because it involves prolonged pre-attachment and conceptus migration phases, and both invasive and non-invasive placental cell types, and as such has been an important comparative model. This study characterised regulation of oestrogen (ER) and progesterone (PR) receptors in the endometrium of the mare during the oestrous cycle and early pregnancy. Endometrial tissues collected duri...
Giguère S, Sweeney RW, Bélanger M.To investigate the pharmacokinetics of enrofloxacin in adult horses. Methods: 2-dose oral and i.v. cross-over trial followed by multiple oral doses. Methods: 8 clinically normal adult horses. Methods: Enrofloxacin was administered at dosages of 2.5 mg/kg of body weight to 4 horses and 5.0 mg/kg to 4 other horses. Each dose was given by the intragastric and i.v. routes, using a cross-over design. After the first intragastric dose, 5 additional doses were administered at 12-hour intervals. Enrofloxacin concentrations were measured in serum, synovial fluid, peritoneal fluid, urine, CSF, and endom...
Thompson RE, Johnson AK, Dini P, Turco MY, Prado TM, Premanandan C, Burton GJ, Ball BA, Whitlock BK, Pukazhenthi BS.The endometrium, the inner uterine lining, is composed of cell layers that come in direct contact with an embryo during early pregnancy and later with the fetal placenta. The endometrium is responsible for signals associated with normal reproductive cyclicity as well as maintenance of pregnancy. In the mare, functionally competent in vitro models of the endometrium have not been successful. Furthermore, the ability to study various reproductive processes in vitro may allow critical evaluation of signaling pathways involved in the reproductive diseases of animals that cannot be handled frequent...
Watson ED.Post-breeding endometritis is a major cause of subfertility in the mare. Endometritis is a normal event in the immediate period after mating, but the presence of ultransonographically visible uterine fluid more than 12 h later is thought to be evidence of uterine pathology. In mares that are free of venerally transmitted endometritis, treatment is aimed at removing the intraluminal fluid. If the endometritis persists past day 5, when the embryo enters the uterine lumen, the cytotoxic environment will not be compatible with pregnancy. Reproductive anatomy, defective myometrial contractility, lo...
Aupperle H, Ozgen SSchoon HA, Schoon D, Hoppen HO, Sieme H, Tannapfel A.The aims of this study were to investigate the steroid hormone receptor expression and the proliferation intensity during the equine endometrial cycle by immunohistological methods, established for routine examination of formalin-fixed, paraplast-embedded specimens. Endometrial biopsy specimens were obtained during one cycle from 7 mares. In comparison with the blood steroid hormone levels the quantity and distribution of oestrogen (ER) and progesterone receptors (PR) and the proliferation marker Ki-67 antigen expression were investigated. Rising 17beta-oestradiol concentrations in preoestrus ...
Fumuso EA, Aguilar J, Giguère S, Rivulgo M, Wade J, Rogan D.Our objective was to characterize immune parameters in susceptible (SM) and resistant (RM) mares, with and without artificial insemination (AI) and immunomodulation. Eight RM and eight SM were selected based on their reproductive history and functional tests. Both groups of mares were evaluated during three consecutive cycles: Cycle 1, untreated cycle (control); Cycle 2, AI with dead semen; Cycle 3, AI with dead semen and immunomodulation. Endometrial biopsies were taken during the three cycles as follows: Cycle 1--at estrus, when follicles > or =35mm and at diestrus (7+/-1 days after ovulatio...
Szóstek AZ, Siemieniuch MJ, Lukasik K, Galvão AM, Ferreira-Dias GM, Skarzynski DJ.Accurate regulation of the reproductive cycle and successful implantation depend on proper functioning of the endometrium. The aim of this study was to determine whether mRNA transcription of specific enzymes responsible for prostaglandin (PG) synthesis (prostaglandin-endoperoxide synthase, PTGS-2; prostaglandin F(2α) synthase, PGFS; and prostaglandin E(2) synthases, PGES) and PG concentrations in endometrial extracts would change in moderate (Kenney's Category II) and severe phases of fibrosis (Kenney's Category III; endometrosis), compared with healthy endometrium (Kenney's Category I), dur...
Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K.Equine endometrial fibrosis (endometrosis) is described as a degenerative chronic condition in the uterus. Its characteristic feature is excessive deposition of extracellular matrix (ECM) components around the endometrial glands and stroma. Although matrix metallopeptidases (MMPs) that mediate ECM turnover are important factors in the process of fibrosis, knowledge of their expression and regulation in endometrosis is limited. In other species, one of the important regulators of MMPs and tissue inhibitors of MMPs (TIMPs) is transforming growth factor (TGF)-β1. The goal of this study was to de...
Troedsson MH, Woodward EM.Equine endometritis is characterized by the expression of pro- and anti- inflammatory cytokines and an influx of polymorphonuclear neutrophils (PMNs) into the uterus. Mares resistant to persistent endometritis clear the inflammation within 24-36 h after exposure to microorganisms or semen. These mares have a rapid increase of pro-inflammatory cytokines and an upregulation of inflammatory modulating cytokines within 6h after exposure to inflammatory challenge. In conjunction with effective uterine contractions, these events are believed to be responsible for the transient nature of the inflamma...
