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.
Hurtgen JP, Ganjam VK.Endometrial biopsy or endometrial biopsy and uterine culture taken on Day 4 after oestrus induced lysis of the corpus luteum (CL), resulting in a sharp decline in serum progesterone concentration and shortened the interoestrous interval in 8/12 and 32/33 oestrous cycles, respectively, during 2 experiments. Cervical dilatation 4 days after oestrus shortened the interoestrus interval in 5/10 and 0/5 oestrous cycles. Endometrial biopsy and culture on Days 1 and 3 after oestrus also induced CL lysis during 4 of 7 cycles. Total oestrogen (oestrone plus oestradiol) concentrations increased at the on...
Pope AM, Campbell DL, Davidson JP.Foal heat was significantly delayed in 15 Thoroughbred and Quarter-horse mares by 200 mg progesterone in oil from Days 5--14 post partum. Nine of these mares subsequently received daily i.v. injections of 2 mg of a synthetic GnRH preparation (AY-24,031) from Day 2 of the progesterone-delayed oestrus but this treatment did not significantly shorten oestrus or hasten ovulation. Uterine biopsies taken on Day 15 post partum from all the mares showed a mixed endometrial morphology having both oestrous and dioestrous characteristics. There was an increased proliferation of endometrial glands in thes...
Hurtgen JP, Whitmore HL.In 10 mares, lysis of the corpus luteum was induced by endometrial biopsy and culture on day 4 after estrus, as evidenced by a sharp decline in serum progesterone concentration and a shortened interestrous interval. Estrus following the manipulations was prolonged. Endometrial biopsy and culture on days 1 and 3 after estrus or manually dilating the cervix on day 4 after estrus also decreased the serum progesterone concentration (within 24--48 hr after manipulation), shortened diestrus, and prolonged the subsequent estrus. In a 2nd experiment, endometrial biopsy on day 4 after estrus shortened ...
Allen WE.Plasma concentrations of sodium benzylpenicillin were measured following intrauterine infusion at a dose rate of 22,000 u/kg (250,000 u/ml). The reproductive status of the mare at the time of infusion did not appear to influence plasma concentrations of penicillin, but preswabbing the endometrium for bacteriological culture resulted in peak plasma concentrations which were nearly twice those found in unswabbed mares.
Digby NJ.Experimental studies of endometrial smears from 26 normal mares showed that after a period of sexual rest exceeding 7 days smears were generally free from inflammatory cells. Smears from 9 mares showing signs of persistent endometritis contained inflammatory cells in 91 per cent while bacterial culture was positive in only 45 per cent. Smears were also taken from 242 Thoroughbred mares as a routine procedure in 1977. It was concluded that endometrial cytology provides a better guide to uterine inflammation than bacteriology. The routine clinical use of endometrial cytology is recommended to ai...
Kenney RM.Normal histologic changes that occurred in concert with the ovarian cycle were evaluated. When combined with behavioral and physical findings, this evaluation enabled determination when there was synchrony between ovarian steroids (estrogen and progesterone) and their target tissues of endometrium. A system for classification as well as definitions of patterns types and degrees of severity of inflammatory and fibrotic changes was developed to facilitate a uniform system for description and communication. An attempt was made to relate the pathologic changes to their effect on fertility when fer...
Allen WR.Fertilized eggs reach the uterus of the mare by the sixth day after ovulation whereas unfertilized eggs remain lodged in the fallopian tubes for many months. However, embryo removal studies indicate that the fetal message for luteal maintenance in the pregnant mare is not transmitted until Days 14-16. The equine endometrial cups comprise a series of small, ulcer-like endometrial outgrowths which are present in the pregnant horn of the uterus between 40 and 150 days of gestation. Each cup consists of a discrete colony of large, gonadotropin-secreting, trophoblast cells derived from a specialize...
Loy RG, Hughes JP, Richards WP, Swan SM.The injection of 100 mg of progesterone/day from Days 5 to 14 after foaling blocked or delayed oestrus and ovulation in 6/9 mares; the remainder ovulated during treatment without showing oestrus. Urinary oestrogen concentrations in these mares were highest between Days 9 and 15 after foaling but the peak levels were only about half those seen in untreated mares during the post-partum oestrus and ovulation. The injection of 200 mg progesterone/day blocked oestrus and ovulation in two mares but did not depress oestrogen excretion maxima any further. Follicles prevented from developing beyond a c...
Hernández-Jáuregui , González-Angulo A.Electron microscopy and immunofluorescence techniques were used to study the various epithelial cells in the endometrial cups of ten pregnant mares, and in the uterine epithelium of one non-pregnant mare. Evidence was obtained which suggested that epithelial gland cells within the endometrial cups, as distinct from the hypertrophied decidual-like cells in the cup, may synthesize PMSG. The suggestion does not agree with the findings of other workers in the fetal origin (chorionic girdle cells) of this gonadotrophin.
Moor RM, Allen WR, Hamilton DW.Biochemical and morphological studies were carried out to determine the origin and histogenesis of endometrial cups in mares. A wide range of fetal and maternal tissues were cultured in vitro and their ability to secrete gonadotrophin (PMSG) was monitored. High levels of PMSG were produced in culture only by cells from the restricted area of the equine trophoblast known as the chorionic girdle which is an annular band of highly specialized cells at the junction of the allantois and the regressing yolk sac. The morphological appearance of girdle cells after cultivation in vitro and after alloge...
Yamauchi S.The luminal and cut surface of endometrial cups were examined by scanning electron microscopy. The distribution of PAS-positive and lipid materials in cup tissue was studied and most of the lipid material was localized in the large polyhedral cup cells. The lipid droplets gave positive reactions for DNPH in the cholesterol test of Schultz. They also exhibited autofluorescence and were therefore considered to be steroidal in nature. The significance of this possibility, particularly with regard to maintenance of early pregnancy in the mare, is discussed.
Hughes JP, Loy RG.Many normally fertile stallions harbour bacteria in and on the genital organs. Many mares served by such stallions are unaffected by the bacteria to which they are thus exposed; however, some mares so exposed will become infected and diseased. Presumably, the genital defenses of such mares had been compromised. Strain differences in pathogenicity of bacteria do exist. Some mares affected with pyometra had irregular ovarian activity and some had normal ovarian cycles. In the former group, destruction of the endometrium many have prevented the production of endogenous luteolysin. The leukopenia ...
van Niekerk CH, Morgenthal JC, Sanders CP, Malan JE.Progesterone concentrations were assayed by a competitive protein-binding technique
in peripheral plasma samples collected twice
daily during four oestrous cycles of three
mares, and once a day during the first seven
weeks of pregnancy in four mares. Large
variations were found in progesterone levels
between morning and evening samples on the
same day in the same mare.
The lowest progesterone concentration
was found about the time of ovulation. Within 24 hours after ovulation the progesterone
concentration increased and two peaks, one
at 5 days and another at 8 days, were found.
Be...
Visutakul P, Bell ET, Loraine JA, Fisher RB.Human chorionic gonadotrophin (HCG), pregnant mare serum gonadotrophin (PMSG) and human menopausal gonadotrophin (HMG) were incubated with varying concentrations of urea at different temperatures for different times.
The luteinizing hormone (LH) activity of HCG was progressively destroyed with increasing concentrations of urea. The degree of inactivation was greater at higher temperatures but the time of incubation did not affect the results.
The follicle-stimulating activity of PMSG was reduced at high urea concentrations; the time of incubation was without effect.
Under the experime...
Visutakul P, Bell ET, Loraine JA, Fisher RB.Human chorionic gonadotrophin (HCG), pregnant mare serum gonadotrophin (PMSG) and human menopausal gonadotrophin (HMG) were incubated with varying concentrations of urea at different temperatures for different times.
The luteinizing hormone (LH) activity of HCG was progressively destroyed with increasing concentrations of urea. The degree of inactivation was greater at higher temperatures but the time of incubation did not affect the results.
The follicle-stimulating activity of PMSG was reduced at high urea concentrations; the time of incubation was without effect.
Under the experime...
Piotrowska-Tomala KK, Jonczyk AW, Szóstek-Mioduchowska A, Hojo T, Żebrowska E, Katila T, Ferreira-Dias G, Skarzynski DJ.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...
Moroni R, Fanelli D, Camillo F, Rota A, Cantile C, Marmorini P, Salamone G, Ori M, Panzani D.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 (...
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...
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...
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...
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...
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...
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 ...
Segabinazzi L, Lisboa FP, Zutter B.Limited response to conventional therapies and rising antibiotic resistance emphasize the need for alternative treatments for infectious endometritis. A recent in vitro study showed promising antimicrobial activity of a commercial uterine cleaning sanitizer (UCS) against endometritis pathogens. However, its safety and efficacy in mares remain untested. Objective: This study aimed to assess the clinical safety of intrauterine infusion of UCS in reproductively sound mares. Methods: Exp. 1. Six healthy mares with endometrial biopsies classified as I or IIA had two intrauterine infusions of UCS pe...
Vallejo-Soto P, Dorado J, Herrera-García R, Álvarez-Delgado C, Gómez-Laguna J, Santiago Á, Manrique M, González Ariza A, León Jurado JM....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...
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...
Amaral A, Cerveira-Pinto M, Santos C, Kordowitzki P, Skarzynski D, Ferreira-Dias G, Szóstek-Mioduchowska A.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-...
Donato GG, Necchi D, Gionechetti F, Ala U, Nebbia P, Robino P, Stella MC, Vandaele H, Pallavicini A, Nervo T.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...
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 ...
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...
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...
Lection J, Schnobrich M, Wagner B, Byron M, Back B, Rollins A, Castro Alves RF, Cheong SH, Diel de Amorim M.To evaluate inflammatory cytokine and chemokine concentrations in endometrial samples collected by cytobrush or swab as a potential screening diagnostic marker for equine endometritis. Unassigned: 88 mares had endometrial samples collected, which included cytobrush, swab, and/or biopsy. Clinical reproductive records, reproductive ultrasound examination, endometrial cytology and culture results, and biopsy grading score were recorded. Fluorescent bead-based multiplex assays for the inflammatory markers interferon-γ, interferon-α, IL-1β, IL-4, IL-10, IL-17A, soluble CD14, tumor necrosis facto...
Scoggin KE, Adlan F, Fedorka CE, Rakha SI, Stout TAE, Troedsson MHT, Ali HE.The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor () expression. The current study investigated the expression of the IGF system components, namely the ligands ( and ), their receptors (, , and ), and their binding proteins ( and s) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediatel...
Sadowska A, Wójtowicz A, Molcan T, Drzewiecka EM, Kaczmarek MM, Słyszewska M, Ferreira-Dias G, Szóstek-Mioduchowska A.Equine endometrosis is a chronic degenerative condition with fibrosis being one of the most significant characteristics. A growing body of evidence indicates the critical role of interleukin (IL)-17 in fibrotic disorders. However, its exact role during equine endometrosis remains to be discovered and explained. The main aim of the current study was to establish the expression of IL-17A signaling components in equine endometria with and without endometrosis as well as the effects of IL-17A on the transcriptomic signature, cellular functional characteristics, expression of extracellular matrix (...
Muderspach ND, Daucke R, Nielsen MW, Scoggin KE, Fedorka CE, Miller LMJ, May MG, Troedsson MHT, Ferreira-Dias G, Agerholm JS, Schoof EM....Endometrial fibrosis leads to subfertility when periglandular fibrosis impairs endometrial gland function. Identifying distinct protein expressions in mares suffering from this condition is essential for understanding the pathogenesis and developing treatments to delay fibrotic progression. To gain a better understanding of protein dynamics underlying this condition, Data-Independent Acquisition Mass Spectrometry was utilized to comprehensively characterize and compare the equine endometrial and plasma proteome from mares with different severities of endometrial fibrosis. Mares in diestrus wer...
Alfatlawy HJ. in Arabian mares poses a significant reproductive challenge, necessitating proper pathogen identification and antimicrobial susceptibility determination. Unassigned: To investigate the prevalence of intrauterine pathogens and their antimicrobial susceptibility patterns in Arabian mares with postbreeding endometritis. Unassigned: Seventeen Arabian mares were examined clinically and ultrasonographically. Uterine swabs were collected for bacterial isolation and antimicrobial susceptibility testing. Unassigned: Clinical endometritis was detected in 29.4% of the mares. Ultrasonographic examination...
Risvanli A, Salykov R, Timurkaan N, Seker I, Ekinci E.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...
Moroni R, Fanelli D, Maltinti S, Orefice M, Rota A, Camillo F, Melanie P, Cantile C, Miragliotta V, Pirone A, Lazzarini G, Passamonti F, Marmorini P....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...
Wójtowicz A, Sadowska A, Myszczyński K, Molcan T, Kaczmarek MM, Szóstek-Mioduchowska A.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...
