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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.
Evidence-based interpretation of uterine cultures in mares: Linking bacterial growth patterns to endometrial inflammation. We evaluated uterine bacterial growth patterns and their association with endometrial inflammation (EI) in equine samples collected using uterine swabs (US) or low-volume uterine lavage (UL). A database including 1,545 US and 2,066 UL with cytological and bacteriological results was retrospectively analysed. Endometrial inflammation was defined as ≥2 polymorphonuclear cells per high-power field, and bacterial culture was considered positive when aerobic growth occurred within 48 h, with the number of bacterial isolates per sample recorded (0, 1, 2, or ≥3). Data were analysed using generali...
Microbiological, Molecular Diagnosis and Antimicrobial Resistance of Bordetella bronchiseptica in the Equine Reproductive Tract in Brazil. The genus Bordetella comprises 16 species of aerobic Gram-negative bacteria, with the most notable being B. pertussis, B. parapertussis and B. bronchiseptica. The latter stands out for its ability to infect various hosts, causing both respiratory and reproductive issues, such as endometritis and infertility in mares. These infections impair reproductive efficiency and facilitate the spread of the pathogen among susceptible animals. Objective: The present study aimed to report the isolation and molecular diagnosis of B. bronchiseptica associated with endometritis and infertility in mares in Bra...
Evaluation of a commercial multiplex immunoassay for assessing uterine inflammation in mares susceptible to persistent breeding-induced endometritis. Persistent breeding-induced endometritis (PBIE) is characterized by a prolonged and dysregulated uterine inflammatory response following breeding. Although inflammatory cytokines are central to the post-breeding immune response, their assessment in the equine uterus has historically relied largely on gene expression analyses. Multiplex immunoassays provide an opportunity to simultaneously quantify multiple cytokine proteins within uterine secretions; however, the application of equine-specific multiplex immunoassays utilizing the Luminex platform to low-volume uterine lavage (LVL) fluid remain...
Intrauterine ozone therapy reduces bacterial load in mares with mixed bacterial endometritis: a longitudinal study. Mixed bacterial endometritis poses a therapeutic challenge in mares due to the coexistence of multiple pathogens with divergent antimicrobial susceptibility profiles. This study evaluated the effects of intrauterine ozone insufflation on uterine bacterial load and endometrial inflammatory response in mares with naturally acquired mixed bacterial endometritis. Fifteen mares with mixed bacterial infection were allocated to two treatment groups: a pathological control group receiving pure medical oxygen insufflation (PC; n = 6) and an ozone-treated group receiving 42 µg/mL ozone for three c...
Interleukin 12 on extracellular matrix-related factors and functional characteristics of equine endometrial fibroblasts. Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a key role, driving the progression of fibrosis. Results of recent study suggest that interleukin (IL)-12 may play a role in the processes associated with the development of fibrosis. This proinflammatory cytokine is synthesized and released by macrophages, dendritic cells, and B cells. Objective: The objective of this study was to determine: (i) the expression of IL-12 and its receptor ...
Matched embryo-endometrium RNA-seq reveals coordinated but asymmetric transcriptomic reprogramming at the onset of early equine pregnancy. Maternal recognition of pregnancy (MRP) in the mare requires coordinated adaptations of both the conceptus and the endometrium during the peri-recognition interval; however, integrated transcriptomic analyses of both compartments within the same biological window remain limited. Here, we analyzed conceptus RNA-seq data across embryonic age (Days 8 and 12 post ovulation) and endometrial RNA-seq data across pregnancy status (pregnant versus non-pregnant mares sampled between Days 8 and 12 post ovulation). In pregnant mares, conceptus recovery and endometrial biopsy collection were performed with...
Exploring the role of epigenetics in the processes related to the development of endometrosis in the mare. Endometrosis is a chronic degenerative condition of the mare endometrium characterized by progressive fibrosis and glandular alterations that impair uterine function and fertility. Its pathogenesis involves persistent inflammation, the activation of myofibroblasts, and the accumulation of extracellular matrix (ECM), leading to disrupted glandular secretion and compromised maintenance of pregnancy. While histopathological studies of endometrosis are well described, the underlying molecular mechanisms remain incompletely understood. Emerging evidence highlights the crucial role of epigenetic reg...
Effect of N-acetyl cysteine treatment on uterine cytokine and chemokine profiles in mares with persistent breeding-induced endometritis. Persistent breeding-induced endometritis (PBIE) is a major cause of infertility in mares. Recent research has shown that PBIE-affected mares treated with intrauterine N-acetyl cysteine (NAC) 12 hours before breeding showed no improvement in clinical signs at 12- and 60-hours post-breeding. Objective: The present study was designed to examine the effects of NAC treatment on the uterine inflammatory cytokine and chemokine profiles in PBIE-affected mares. Methods: Using a randomized, blinded, cross-over design, mares susceptible to PBIE (n=9) were allocated to Control and Treatment cycles with at...
Ovarian follicle dynamics in the plains zebra (Equus quagga). Understanding follicular dynamics during the estrous cycle is essential for developing breeding programs and assisted reproductive technologies (ARTs) in any species. In this context, knowledge of follicular dynamics and related uterine changes in the plains zebra (Equus quagga) is essential to increase the declining population of this vital African species and to provide comparative insights into more endangered zebra species. Likely due to the difficulty of handling these wild species, no detailed reproductive study using ultrasonography has been performed in any zebra. Therefore, the presen...
Verminous mastitis caused by Cephalobus cubaensis infection in a mare. A 7-y-old American Quarter Horse mare was presented to a veterinary hospital for ongoing reproductive monitoring and management of endometritis. During physical evaluation, several nodular lesions of unknown origin and duration were discovered in the mammae. Histologically, biopsies from the lesions were confirmed as severe granulomatous mastitis with intralesional rhabditid nematodes. A putative diagnosis of or infection was assigned, and ivermectin (1.2 mg/kg PO) treatment was given every 2 wk. When lesions persisted after the initial dose of ivermectin, PCR testing of and gene targe...
Age, embryo donor status, and insemination with chilled semen all predispose to persistent breeding-induced endometritis in warmblood mares. Persistent breeding-induced endometritis (PBIE) is a common reason for mares failing to establish pregnancy. Objective: To examine the hypothesis that advancing mare age and embryo donor status predispose to PBIE and compromise fertility. Methods: Retrospective analysis of the impact of mare age, breeding system (embryo donor versus broodmare), and semen type (chilled versus frozen-thawed) on the likelihood of PBIE and subsequent pregnancy/embryo recovery. Methods: Warmblood mares (n = 769) inseminated during 1745 oestrous cycles were divided into three age categories (≤6, 7-13 and ≥14...
Relationship between the estrus duration in cyclic mares and the endometrial gene expression on day 7 post-ovulation. This study investigated the effect of estrus duration on endometrial gene expression in cyclic mares on Day 7 post-ovulation, focusing on transcripts relevant to early pregnancy: uterocalin (P19), insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2), progesterone receptor (PGR), and estrogen receptor alpha (ESR1). Twelve mares were classified according to the estrus duration in long estrus (LE, ≥ 3 days of endometrial edema; n = 7) or short estrus (SE, 0.1). ESR1 expression was undetectable in all samples. These findings suggest that prolonged estrus enhances P19 e...
Milk fat globule EGF and factor V/VIII domain containing (MFGE8) as a novel player in equine endometrial fibrosis. With increasing age, mares are frequently affected by endometrial fibrosis. Transforming growth factor beta 1 (TGF-β1) promotes fibrosis, while milk fat globule EGF and factor V/VIII domain containing (MFGE8) primarily exerts antifibrotic effects. We used in situ hybridization analysis (ISH) to investigate MFGE8, TGFB1 and its downstream effectors cellular communication network factor 2 (CCN2) and transgelin (TAGLN) in equine endometrial fibrosis. Additionally, transcriptional effects of TGF-β1 and MFGE8 on equine endometrial fibroblasts in vitro were investigated by single cell sequencing. ...
Molecular typing, biofilm characteristics and biofilm-targeted inhibition strategies of Streptococcus equi subsp. zooepidemicus isolated from donkey endometritis. Endometritis is a major cause of infertility in intensively farmed donkeys. Streptococcus equi subsp. zooepidemicus (SEZ) is a predominant pathogen that readily forms biofilms in equine endometritis, conferring resistance to conventional treatments. Objective: This study aimed to characterize the biofilm dynamics of SEZ isolates obtained from donkeys and to evaluate potential anti-biofilm strategies with different drug combinations. Methods: Uterine lavage samples were collected from 30 Dezhou Black donkeys with clinical endometritis. Bacterial cultures were performed on blood agar and MacConk...
Comparative analysis of uterine inflammation in jennies and mares after insemination with cryopreserved donkey semen. The limited fertility of jennies inseminated with frozen donkey semen remains a major challenge for donkey reproduction and conservation, contrasting with the more favorable outcomes observed in mares. Species-specific differences in post-breeding uterine inflammation have been proposed as a key factor underlying this disparity. This study compared the uterine inflammatory response and pregnancy outcomes of jennies and mares inseminated with frozen donkey semen. Twelve jennies and eleven mares were monitored over 48 and 44 estrous cycles, respectively. Artificial insemination (AI) was performe...
Relationship between the duration of endometrial edema and reproductive parameters of estrus, diestrus, and fertility in mares: a field study. The duration of endometrial edema has been positively correlated with uterine receptivity and likelihood of pregnancy. Therefore, this study aimed to evaluate whether there is a relationship between the duration of endometrial edema (DEdema) and other key parameters of the estrous cycle: maximum edema (MEdema), largest follicle diameter (LPF), corpus luteum and uterine tone on day 5 post ovulation (CLD5 and TD5), progesterone concentration (P4) and fertility. A total of 88 cycles from 36 mares were evaluated and divided into Short Estrus (SE), Long Estrus (LE), Inseminated (AI) and Non-insemin...
Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells. Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment an...
Confocal laser endomicroscopy: exploring endometrial image quality in relation to the oestrous cycle of mares. Assessment of the endometrium is an essential component of a breeding soundness examination in mares. The current reference standard for evaluating equine endometrial health is histopathological assessment of an endometrial biopsy, however, inconsistencies may arise when a single blinded biopsy is used. Confocal laser endomicroscopy (CLE) is non-invasive and enables real-time in-vivo imaging of the endometrium across multiple locations within the uterine lumen. An initial study revealed variation in CLE image quality between mares. Objective: This study aimed to compare the quality of endometr...
TGF-β1 and estradiol modulate prostaglandin concentrations and related gene expression in equine endometrium during the follicular phase. Transforming growth factor (TGF)-β1 is a pro-fibrotic cytokine that affects extracellular matrix (ECM) deposition and fibroblast activity. 17β-Estradiol (E), the dominant ovarian steroid during the follicular phase (FLP) of the estrous cycle, can also influence ECM remodeling and fibrosis, through prostaglandin (PG) synthesis. PGs have opposing roles in fibrosis, with PGE₂ showing anti-fibrotic effects and PGF₂α promoting fibrosis. Equine endometrosis, whose main pathological feature is fibrosis, is marked by chronic inflammation and ECM accumulation, and may involve mediators like TGF-...
Characterization of the Endometrial Microbiota of Healthy Mares Across the Estrous Cycle. In the past, bacteria detected in the mare's uterus were generally interpreted as a sign of endometritis, since the uterus was considered a sterile environment. This assumption has been challenged by the introduction of culture-independent molecular techniques, particularly 16S rRNA amplicon sequencing, which have demonstrated that healthy mares harbor an endometrial microbiota. The aim of this study was to characterize the endometrial microbiota of healthy mares and to determine whether microbial composition differs between estrus and diestrus. Endometrial samples were collected from eleven h...
Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment. Equine chronic degenerative endometritis (CDE) is a progressive process characterized by endometrial fibrosis that could be responsible for alterations of uterine environment and foetal-maternal communication. Objective: The aim of this study was to try to restore this communication by intrauterine administrations of amniotic cell-derived extracellular vesicles (AMC-EVs) in a case series. Methods: Twelve mares were selected on the basis of their reproductive history of early embryonic loss or abortion and clinical suspicion of CDE subsequently verified with histopathological examination of end...
A rare and unusual case of advanced complete molar pregnancy in an Arabian mare: first report. Molar pregnancy is a rare condition in women, referring to the development of fetal membranes with or without an embryo. A 22-year-old mare referred to the veterinary faculty clinic due to the delayed parturition. In the ultrasound examination, the uterine membranes were seen suspended in fluids without any trace of the fetal organs. The mare underwent caesarean section, a mixture of brown fluid with fragments of fetal membranes was removed, but no fetus or any remnants of the fetus were found in the uterus. In the histopathological examinations, the fetal membranes showed severe degenerative ...
Effects of intrauterine ozone insufflation in eleven subfertile mares: a case series. Equine persistent breeding-induced endometritis can lead to chronic uterine inflammation and fibrosis, reducing fertility. Intrauterine ozone (O₃) has recently been proposed as a potential treatment for mares unresponsive to conventional therapies. This case series describes O₃ treatment in eleven mares barren for at least one year despite multiple inseminations attempts. During the first oestrous cycle, low-volume uterine lavage and endometrial biopsy were performed, followed by 3 consecutive days of intrauterine O₂-O₃ gas insufflation. In the subsequent cycle, both procedures were re...
Histomorphometric Analysis of the Endometrium of Jennies (Equus asinus) and Mares (Equus caballus) in Estrus: Anatomical Differences and Possible Reproductive Implications. Assisted reproductive techniques are often extrapolated from horses to donkeys, despite poorer fertility outcomes in jennies. This issue has been attributed to unknown uterine species-specific differences. This study compared, through histomorphometry, the endometrium of jennies and mares. Endometrial biopsies (N = 12) were taken from reproductively sound jennies (n = 6) and mares (n = 6) in estrus. Histomorphometric analysis evaluated luminal (LE, µm) and glandular epithelium height (GE, µm), glandular lumen diameter (LD, µm), glandular area (GA, µm), the number of glands (#G), and glandu...
Changes in Uterine Glandular Composition in Kyrgyz Breed Mares According to Pregnancy Status. This study was conducted to examine glandular histological changes in the uterus of Kyrgyz breed mares during the first 6 months of pregnancy. The study used 53 Kyrgyz breed mares; 43 of these were at different stages of pregnancy, while 10 were non-pregnant mares. Uterine samples obtained at the slaughterhouse were evaluated histomorphometrically; endometrial thickness, gland density, gland epithelial height and gland diameter were measured. In conclusion, it was concluded that in Kyrgyz mares, endometrial thickness, glandular epithelial height and diameter increased as pregnancy progressed...
Histomorphometric characterization of the endometrium in mules (Equus mulus): An approach to endometritis/endometrosis. Mules (Equus mulus), as sterile hybrids between mares and donkeys, present a unique uterine morphology and physiology that remains poorly characterized. This study provides the first histomorphometric evaluation and transcriptional profiling of the endometrium in adult mules. To achieve this, endometrial biopsies were analysed using quantitative stereology, histological classification (Kenney-Doig system), and qPCR of key immune-related and fibrotic genes. Histometric analyses revealed that the stratum spongiosum was the predominant component of the mule endometrium (mean volume density: 84.7...
Towards understanding mare endometrosis: ex vivo study on the role of relaxin. Mare endometrosis remains a poorly understood pathological process. Objective: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H), or treated with vehicle (Hveh), and tissues with endometrosis that were left untreated (E), treated with vehicle (Eveh), and treated with RLX (10, 25, 50 nM; ER) were used for an ex vivo system for 72 h. Methods: Tissue histological examination, and immunoenzymatic measurement of the concentrations of transforming growth factor β (TGF-β), interleukins (IL-6 and IL-8), and pr...
Uterine proteomic and cytokine profiling show that Streptococcus equi subsp. zooepidemicus induces immune-metabolic dysregulation and may predispose mares to endometrosis. This study aims to characterize and compare the uterine fluid proteome and cytokine profile of reproductively healthy mares (HM; n = 15) and mares with Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)-associated endometritis (SAE; n = 9). Uterine flush samples collected during the follicular phase were analyzed by shotgun proteomics and multiplex cytokine assays. Equine proteins were mapped to human orthologs, and enrichment and network analyses were performed using g:Profiler, Metascape, ToppGene, and STRING/MCODE. SAE mares showed higher levels of IL-1α, IL-1β, GRO, IL12p...
Transcriptomic Insights into Tumor Necrosis Factor α’s Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts. Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNFα in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of...
Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Mare endometrosis is a chronic degenerative condition of the endometrium, primarily characterized by fibrosis, involving interactions among fibroblasts, immune cells, and epithelial cells regulated by cytokines and growth factors. T helper (Th)1 and Th2 cells seem to play a pivotal role in fibrosis. However, their roles in equine endometrial fibrosis remain unknown. This study explores Th1 and Th2 cell distribution across different stages of endometrium histopathological Kenney and Doig categories; and evaluated their secretome effects on non-fibrotic endometrium derived fibroblast functional ...
