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.
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...
Kolm G, Klein D, Knapp E, Watanabe K, Walter I.Lactoferrin (LF) is an estrogen-regulated glycoprotein with well-described antibacterial and immunomodulatory properties. The present study is the first report on LF expression in horse endometrial specimens. Mares chosen for the study were either resistant or susceptible for persisting mating-induced endometritis (PMIE) during the natural ovulatory cycle and in early pregnancy. Our investigations included immunostaining for LF protein and CD18, a leukocyte marker, as neutrophils are a possible source for LF in the endometrium. Quantification of LF mRNA was performed by use of real-time RT-PCR...
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.
Roberto da Costa RP, Ferreira-Dias G, Mateus L, Korzekwa A, Andronowska A, Platek R, Skarzynski DJ.Nitric oxide (NO) plays an important role in angiogenesis and in the regulation of the blood flow. This study was carried out to investigate (i) the effects of endogenous estrogens and progestins and exogenous progesterone (P(4)) (5 ng/ml or 1 microg/ml) or estradiol 17beta (E(2)beta) (50 pg/ml or 1 microg/ml) on in vitro endometrial NO synthesis; (ii) the presence of different isoforms of NO synthase; (iii) and their relationship to microvascular density in the equine endometrium during the estrous cycle. NOS expression was also evaluated in the myometrium. Expression of endothelial and induc...
Aguilar J, Hanks M, Shaw DJ, Else R, Watson E.Material for endometrial cytology can be collected by veterinarians using guarded or unguarded swabs, or digitally with a gloved hand, and is an important diagnostic tool in establishing the endometrial health of mares prior to breeding. The aim of this study was to determine whether the use of unguarded endometrial samples is a reliable indicator of the presence of neutrophils in the uterus. Duplicate endometrial smears were collected from 41 genitally normal, non-pregnant fertile mares by both double-guarded swabs (DGS) and in an unguarded manner by digital scraping (DS) of the endometrium. ...
Abd-Elnaeim MM, Leiser R, Wilsher S, Allen WR.This investigation was carried out to study the equine placenta from early gestation to near term, with special reference to morphological changes associated with the development of the vasculature of the fetal component of the microcotyledons. Pregnant uteri were removed post mortem from five Thoroughbred mares between 110 and 309 days of gestation, two of which were aged, multiparous animals suffering age-related degenerative changes in their endometrium (endometrosis), while the other three were young, and had primigravid normal healthy uteri. Pieces of endometrium with placenta attached we...
Ganjam VK, Evans TJ.Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measure...
Lefebvre R, Theoret C, Doré M, Girard C, Laverty S, Vaillancourt D.An 8-year-old Arabian mare was admitted for a large ovarian anovulatory follicle. A clinical diagnosis of ovarian tumor and endometritis was established. Histological examinations revealed an ovarian teratoma and a grade II endometritis. Three months after unilateral ovariectomy, the mare was confirmed pregnant and eventually gave birth uneventfully. Une jument Arabe de 8 ans fut présentée pour un gros ovaire. Un diagnostic de tumeur ovarienne et d’endométrite fut posé. L’examen histologique confirma un tératoma ovarien et une endométrite grade II. Trois mois après une ovariectomie...
Hemberg E, Lundeheim N, Einarsson S.Changes in the conformation of the vulva predispose the mare to uterine infection. Vulvoplasty for closure of the upper vulvar lips improves fertility. Not all mares are resutured after parturition, but are resutured after mating. No clinical data have hitherto been published on the reproductive outcome in mares that are resutured or not after parturition. The objectives of the present study were to investigate relationships between vulvar status (not Caslick-operated, group A; previously Caslick-operated and/or not resutured after the last parturition, groups B and C respectively) and endomet...
Silva LA, Ginther OJ.The spherical equine embryonic vesicle is mobile throughout the uterine lumen for several days before becoming fixed in the caudal segment of a uterine horn on Day 16 (ovulation = Day 0). Orientation refers to the position of the embryo proper at the periphery of the vesicle relative to the position of the mesometrial attachment. In mares, the embryonic pole of the vesicle is antimesometrial after completion of orientation. Day of vesicle fixation, differential thickening of the endometrium near the mesometrial attachment, and orientation of the embryonic vesicle were studied in 30 ponies, usi...
Causey RC.Equine uterine infections inflict major losses on the equine industry. Persistent inflammation of the oviduct and uterus leads to loss of the conceptus and mares susceptible to infection have weakened uterine defences partly due to retention of inflammatory exudate. Bacteria may trigger inflammation, resist phagocytosis, or adhere to the endometrium and types of infection range from genital commensals in susceptible mares to reproductive pathogens in normal mares. Uterine infections are diagnosed by history, detection of uterine inflammation, and isolation of typical organisms and susceptible ...
Adams AR, Haines GR, Brown MP, Gronwall R, Merritt K.Pharmacokinetics of difloxacin and its distribution within the body fluids and endometrium of 6 mares were studied after intragastric (IG) administration of 5 individual doses. Difloxacin concentrations were serially measured in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal fluid, and endometrium over 120 h. Bacterial susceptibility to difloxacin was determined for 174 equine pathogens over a 7-month period. Maximum serum concentration (Cmax) was 2.25 +/- 0.70 microg/mL at 3.12 +/- 2.63 h and Cmax after the 5th dose was 2.41 +/- 0.86 microg/mL at 97.86 +/- 1.45 h. The mean elim...
Arai KY, Tanaka Y, Taniyama H, Tsunoda N, Nambo Y, Nagamine N, Watanabe G, Taya K.In this study, the expression patterns of inhibins, activins, insulin-like growth factor-I (IGF-I) and steroidogenic enzymes in equine placentae recovered during the latter two-thirds of gestation were examined. Concentrations of inhibin A and inhibin pro-alphaC in endometrial and fetal placental tissue homogenates were very low during the period examined, whereas these tissues contained high concentrations of activin A. In both maternal endometrial and fetal placental tissues, activin A levels decreased as pregnancy progressed. Expression of inhibin alpha-subunit was not observed in the place...
Walter I, Handler J, Miller I, Aurich C.Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix pr...
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...
Card C.Endometritis has been reported to be the third most common medical condition of horses. Timely diagnosis and treatment of endometritis in mares increases the chance of pregnancy. Exfoliative endometrial cytology is often used as a clinical tool to evaluate endometrial inflammation through detection of neutrophils. There is a lack of information on the time frame for changes in endometrial cytologic parameters following breeding. The main objectives of this article are to use current information to describe systematic analysis of endometrial cytology using standardized methods for sample collec...
Nielsen JM.The objective of this study was to compare results from endometrial culture swabs with results from culturing of endometrial biopsies. The culture results were related to cytological findings (polymorphonuclear; PMN-cells) and histological observations (PMN-cells). Biopsy and swab samples were smeared on the surface of a blood agar petri dish, and examined for growth of bacteria. Cytology samples were obtained from endometrial biopsies, stained and examined under microscopy for the presence of PMN-cells. Endometrial biopsies were examined for the presence of PMN-infiltration of the endometrial...
Welter H, Bollwein H, Weber F, Rohr S, Einspanier R.The expression of the endothelial and inducible nitric oxide synthases (eNOS and iNOS, respectively) was examined in the endometrium of cyclic and pregnant mares by real-time polymerase chain reaction and immunohistology. The concentration of eNOS mRNA varied throughout the oestrous cycle, with significantly higher transcripts on Day 5 of the oestrous cycle (P 0.05). In early pregnant mares both eNOS and iNOS mRNA increased between Days 12 and 15 (P < 0.05). In cyclic mares, eNOS protein was detected immunocytochemically in endometrial epithelia, the basement membrane, the endothelial laye...
Flaminio MJ, Antczak DF.At days 36-38 of gestation, the equine invasive trophoblast cells migrate into the endometrium of the pregnant mare to form the endometrial cups. During their migration, they become surrounded by maternal CD4+ and CD8+ T lymphocytes, and stimulate a cytotoxic antibody response to the paternal major histocompatibility complex class I antigens that they express. Nevertheless, endometrial cup cells remain viable at the site of uterine invasion up to days 80-100 of gestation, suggesting the participation of immunomodulatory mechanisms to the maternal cellular immune response. To determine the effe...
Güvenc K, Reilas T, Katila T.It is unclear whether AI of mares deep into the uterine horn causes more or less inflammation of the endometrium than conventional AI. Thus, we compared uterine inflammatory reactions of mares inseminated with two different doses of frozen-thawed semen into the tip of the uterine horn (UH) ipsilateral to the preovulatory follicle with those of mares inseminated into the uterine body (UB). Thirty-two mares were assigned to one of four groups (eight mares/group): UB20=AI into UB, 20 x 10(6)sperm/0.5 mL; UB200=AI into UB, 200 x 10(6)sperm/0.5 mL; UH20=AI into UH, 20 x 10(6)sperm/0.5 mL; UH200=AI ...
Silva LA, Gastal EL, Beg MA, Ginther OJ.The equine embryonic vesicle is mobile on Days 12-14 (Day 0 = ovulation), when it is approximately 9-15 mm in diameter. Movement from one uterine horn to another occurs, on average, approximately 0.5 times per hour. Mobility ceases (fixation) on Days 15-17. Transrectal color Doppler ultrasonography was used to study the relationship of embryo mobility (experiment 1) and fixation (experiment 2) to endometrial vascular perfusion. In experiment 1, mares were bred and examined daily from Day 1 to Day 16 and were assigned, retrospectively, to a group in which an embryo was detected (pregnant mares;...
Al-Bagdadi FK, Eilts BE, Richardson GF.Scanning electron microscopy (SEM) was used to study the endometrium of nine 1-year-old thoroughbred mares after twice intrauterine infusions of gentamicin, on 2 consecutive days. Five mares were infused on 2 consecutive days with 40 ml gentamicin (50 mg/ml) mixed with 80 ml of normal saline. Four mares served as controls and were infused with 120 ml of saline on 2 consecutive days. Endometrial biopsies were obtained from all mares 3 days after the second intrauterine infusion. Each biopsy was processed for SEM by standard methods. The endometrial epithelium of the gentamicin-infused mares had...
Raeside JI, Christie HL, Renaud RL, Waelchli RO, Betteridge KJ.Because estradiol (E(2)) production by the early equine conceptus is considered crucial to the establishment of pregnancy, the amounts of E(2), estrone (E(1)), and their sulfates (E(2)S, E(1)S) were measured by RIA in yolk-sac fluid of 63 conceptuses collected by transcervical lavage over the period of 11-26 days after ovulation. Amounts increased significantly with age of conceptus, especially for E(1)S. Then, the metabolism of E(2), which may be highly relevant for its action, was examined in the conceptus and endometrium over the period when the conceptus ceases to migrate within the uterus...
Zerbe H, Engelke F, Klug E, Schoon HA, Leibold W.An endometritis model was used to investigate the influence of degenerative endometrial changes (endometrosis) on functional parameters of uterine neutrophils in the horse. Six hours after intrauterine application of recombinant human interleukin-8 (rhIL-8), the uteri of 15 mares were flushed with phosphate-buffered saline. Quantitative and qualitative flow cytometric assays were then made to determine the absolute numbers, viability, phenotype, generation of reactive oxygen species (ROS), and phagocytic activity of immigrated polymorphonuclear neutrophilic granulocytes (PMN). Recombinant hIL-...
Aupperle H, Schoon D, Schoon HA.The aim of this study was to investigate the expression of the intermediate filaments cytokeratin, vimentin and desmin in the equine endometrium by immunohistological techniques. For this purpose, endometrial biopsies of 151 mares were examined to determine physiological cycle patterns and changes resulting from endometriosis. During the physiological cycle epithelial cells and mesenchymal cells express cytokeratin and vimentin, respectively, whilst desmin and vimentin were coexpressed by the smooth muscle cells. Epithelial coexpression of cytokeratin and vimentin was seen in numerous fibrotic...
Walter I, Helmreich M, Handler J, Aurich C.Chronic degenerative disease of the mare's endometrium is characterised by changes in the uterine glands, including cystic dilation, hyperplasia and periglandular fibrosis. Endometrial biopsies were taken from 23 mares with different grades of endometrial degeneration. Solid structures were identified within the lumina of the uterine glands and shown to be calcified by histochemical staining. Most of them were not homogenous but composed of a mixture of mineral and organic substances. Further examinations of these mineralised structures by immunohistochemical methods revealed the presence of t...
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...
Mansour GD, Henry M, Ferreira AM.This study was designed to identify the distribution of type IV collagen, laminin, and fibronectin with an avidin-biotin method in sections of equine endometrial samples, fixed in Bouin's solution and embedded in paraffin wax. Thirty endometrial biopsies were collected at three different stages of the oestrous cycle. The basement membrane of luminal epithelium reacted positively with antibody against type IV collagen. Both type IV collagen and laminin were found in the basement membranes of endometrial glands, and fibronectin occurred diffusely in the interstitial tissue. Blood vessels express...
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 ...
Freeman KP, Roszel JF, Slusher SH, Castro M.Histochemical stains were applied to six equine uterine biopsies representative of the physiologic breeding season, Spring and Fall transition, and Winter anestrus periods. These were compared with uterine biopsies from six mares with intrauterine urine pooling, eight mares used to study the uterine response to indwelling catheterization, and necropsy specimens from four pregnant mares at approximately 60 or 100 d of gestation. Alcian blue staining at pH 2.5 or 1.0 was used to identify the presence of carboxylated and sulfated acid mucins or only suflated acid mucins, respectively. Periodic ac...
Brown MP, Gronwall RR, Houston AE.Six healthy adult mares were each given an oral loading dose of ormetoprim(OMP)-sulfadimethoxine (SDM) at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg, followed by four maintenance doses of 4.6 mg of OMP/kg and 22.9 mg of SDM/kg, at 24 h intervals. Ormetoprim and SDM concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid, urine and endometrium. The highest mean serum OMP concentration was 0.92 micrograms/mL 0.5 h after the first dose; the highest mean SDM concentration was 80.9 micrograms/mL 8 h after the first dose. The highest mean synovial fluid c...
Silva ESM, Vaz IS, Rodrigues TS, Brandão FZ, Oquendo PS, Oquendo FMG, Beletti ME, Cuervo-Arango J.Uterocalin (P19) is a lipocalin protein that has binding activity for the provisioning of the embryo with lipids, including those essential for morphogenesis and pattern formation. Therefore, it is thought that P19 plays an important role in supporting the survival of the early embryo. Previous research has shown that the endometrium from acyclic mares expressed more P19 following a simulated long estrus: treatment of 8 mg of estradiol benzoate (EB) split over five consecutive days, followed by long-acting progesterone administration (LA-P4) 72 hours later, when compared to a single 2.5 mg EB ...
Cazales N, Estradé MJ, Pereyra F, Fiala-Rechsteiner SM, Mattos RC.This study aimed to determine whether the insemination site and dose with cryopreserved sperm of reproductively normal mares affect the sperm population in uterine tubes and the intensity of endometrial inflammatory response. Experimental subjects were estrous mares inseminated, in the mid-uterine body (Body) or the tip of the uterine horn (Tip), ipsilateral to the dominant follicle, with one 0.5 mL straw with 50 × 106 sperm (50) or with eight straws with 50 × 106 sperm/straw (400). Mares were slaughtered 2 h, 4 h and 12 h after artificial insemination (AI) and randomly assigned to f...
Schumacher J, Schumacher J, Blanchard T.The endometrial response of mares to repair of third-degree rectovestibular lacerations was evaluated. Endometrial biopsy specimens from 8 mares with third-degree rectovestibular laceration were obtained immediately before surgery and from 9 to 15 days after repair. Presurgical endometrial biopsy specimens were classified as category I for 2 mares; category II, attributable to slight endometritis, for 5 mares; and category III, attributable to moderate-to-severe endometritis, for 1 mare. Within 15 days after rectovestibular repair, all endometrial biopsy specimens were classified as category I...
Ababneh MM, Troedsson MH.The aim of this study was to determine phospholipase A2 (PLA2) kinetics and activity in the mare's endometrium during the oestrous cycle and early pregnancy. Phospholipase A2 is responsible for the liberation of arachidonic acid from phospholipids, which is the first limiting step in prostaglandins synthesis. Phospholipase A2 activity was measured using an assay based on the liberation of oleic acid from 1-palmitoyl-2-[(14) C] oleoyl phosphatidylcholine. The enzyme was shown to be calcium dependent, to have an optimum pH of 8 and an apparent Michaelis constant of 127 μM. Enzyme activity was l...
Ferreira-Dias GM, Serrão PM, Durão JF, Silva JR.To document uterine growth and microvascular development in the endometrium of uteri with differing degrees of fibrosis as well as uterine growth throughout the estrous cycle of mares. Methods: 30 mares. Methods: Uterine tissue was obtained during the breeding season from a slaughter facility. Stage of estrous cycle of the mares was assessed on the basis of ovarian structures and plasma progesterone concentrations. Endometrium was characterized by use of light microscopy, and blood vessel walls were marked by histochemical techniques. Microvascular development was evaluated by a computerized i...
Araki M, Ohtaki T, Kimura J, Hobo S, Taya K, Tsunoda N, Taniyama H, Tsumagari S, Nambo Y.Immunohistochemical investigations of the expression of surfactant protein A (SP-A) and surfactant protein D (SP-D) in the uterine and placental tissues of 13 pregnant mares were performed using anti-horse monoclonal primary antibodies. Strong positive reactions for both SP-A and SP-D were observed in the trophoblasts in the microcotyledons of the placentae at 182 to 314 days of gestation; in uterine glandular epithelial cells, faint-to-weak reactions were observed during gestation. This study describes, for the first time, the changes in the SP-A and SP-D expression levels in the endometrium ...
Annandale A, Stroehle RM, Schulman ML, Sibeko-Matjila KP, Fosgate GT, Handler J, Vemming DC, Clift SJ.Persistent breeding-induced endometritis (PBIE) or delayed uterine clearance (DUC) are major causes of mare subfertility. Oxytocin and its receptor are thought to play significant roles in the pathogenesis of DUC but the specific roles of oxytocin receptor (OR) distribution and gene expression remain undefined. In this study both OR distribution and gene expression in the endometrium, myometrium and cervix during both luteal and non-luteal phases in non-pregnant mares (n = 27) of differing age (young: 2-9 years, n = 17; old: > 10 years, n = 10) and endometrial biopsy score were ...
Wilsher S, Gower S, Allen WR.Previous reports documenting progesterone receptors (PR) and oestrogen receptors (ER) in the endometrium of early pregnant mares included specimens only up to Day 20 post ovulation. This study aimed to localise PR and ERα on equine feto-maternal tissues between Days 20 and 68 to encompass the period around fixation of the conceptus, development of the endometrial cups and attachment and initial interdigitation of the allantochorion. During early pregnancy mares had the same pattern of PR in the endometrium as that reported for other mammals; namely, a loss of PR from the endometrial epithelia...
Antczak DF, Allen WR.There is little evidence for maternal immunological recognition of pregnancy in most species with the striking exception of the members of the genus Equus. Almost all mares make strong cytotoxic antibody responses to paternally inherited fetal antigens by Day 60 of gestation. Most of these responses are directed against antigens of the Major Histocompatibility Complex (MHC), which constitutes the primary immunogenetic barrier to successful organ transplantation. The source of fetal MHC antigens in the pregnant mare appears to be the specialized trophoblast cells of the chorionic girdle region ...
Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G.Cathepsin G (CAT) is a protease released by neutrophils when forming neutrophil extracellular traps that was already associated with inducing type I collagen (COL1) in equine endometrium in vitro. Endometrosis is a fibrotic condition mainly characterized by COL1 deposition in the equine endometrium. The objective was to evaluate if noscapine (an alkaloid for cough treatment with anti-neoplastic and anti-fibrotic properties) would reduce transcription (evaluated by qPCR) and COL1 protein relative abundance (evaluated by western blot) induced by CAT in equine endometrial explants from follicula...
Caissie MD, Gartley CJ, Scholtz EL, Hewson J, Johnson R, Chenier T.Persistent breeding-induced endometritis (PBIE) is a major cause of infertility in mares. Endometrial inflammation that persists until embryonic descent ultimately results in early embryonic death. A poor endometrial biopsy grade (IIb or III) has been identified as a risk factor for PBIE. Intrauterine fluid accumulation (>2 cm in depth), pathologic endometrial edema, and elevated intrauterine neutrophil levels are all clinical features of PBIE. Commonly applied treatment options include uterine lavage and oxytocin therapy. N-acetyl cysteine (NAC), a mucolytic used to treat bacterial endome...
Davies Morel MC, Lawlor O, Nash DM.Endometritis is an important cause of sub-fertility in mares. The critical indicator of reproductive success and financial return for commercial studs is live foaling rate. Endometrial bacteriology and/or cytology are used to diagnose endometritis and thus identify mares at risk of early embryonic death. However, mares with endometritis may conceive but then abort in late gestation. The aims of this study were to establish, as part of a standard breeding examination (1) whether a threshold percentage of uterine polymorphonuclear neutrophils (PMNs) exists above which a significant reduction in ...
Watson ED, Buckingham J, Björkstén T, Nikolakopoulos E.The presence of oxytocin in the mare uterus was determined by radioimmunoassay of tissue extracts and uterine lavage fluid, and by immunohistochemistry. Samples were obtained from mares during the oestrous cycle and on day 14 of pregnancy. Immunoreactive oxytocin was detected in extracts of endometrium and myometrium, and in uterine lavage fluid. In tissue sections, the luminal epithelium, the epithelium of the superficial, but not deep, glands, blood vessel walls and myometrium all stained positively for oxytocin, whereas only the luminal epithelium and epithelium of the superficial glands st...
Leisinger CA, Klein C, Markle ML, Premanandan C, Sones JL, Pinto CRF, Paccamonti DL.Aluteal cycles were induced in the mare to evaluate the effects of progesterone deprivation on the gene expression of embryos and endometrium collected eight days after ovulation. We hypothesized that the transcript expression would be altered during induced aluteal (AL) cycles (low progesterone <1 ng/mL) when compared with control cycles during diestrus (high progesterone; > 4 ng/mL) for 1) the embryonic expression of progesterone-mediated transcripts and those related to normal embryo growth and development and 2) the endometrial expression of progesterone-mediated transcripts and those ...
Gerstenberg C, Allen WR.Branched tubular endometrial glands are key features of the uterine lining in mares. The epithelium in the neck regions of the glands is similar to that lining the lumen of the uterus, whereas the epithelium in the deeper, coiled portions of the glands secretes protein rich histotrophe or 'uterine milk' during dioestrus and pregnancy. The present study was performed to characterize endometrial histology in perinatal and peripubertal fillies and to investigate the influences of specific steroid treatments on endometrial gland development in the prepubertal period. Uteri obtained from equine fet...
Diel de Amorim M, Bramer SA, Rajamanickam GD, Klein C, Card C.Our objectives were to examine changes in endometrial and luteal gene expression during estrus, diestrus, pregnancy and treatments to induce luteolysis and putatively induce luteostasis. Groups were: Diestrus (DIEST), Estrus (ESTR), Pregnant (PREG), Oxytocin (OXY), Carbetocin (CARB), and Meclofenamic acid (MFA). Blood was obtained from day (D)12 to D15 for measurement of oxytocinase, also referred to as leucyl-cysteinyl aminopeptidase (LNPEP) and progesterone. Luteal biopsies were obtained on D12 and D15 and an endometrial biopsy on D15. Real-time RT-PCR was performed for the following genes: ...
Nash DM, Sheldon IM, Herath S, Lane EA.Mating-induced endometritis (MIE) is ubiquitous in the horse after natural mating and artificial insemination with frozen/thawed semen causing the most aggressive response. The majority of mares eliminate MIE 24-48 h after insemination. An endometrial explant culture was tested as a potential in vitro exemplar for sperm-induced MIE. Endometrial prostaglandin F(2alpha) (PGF(2alpha)) secretion and expression of interleukin-8 (IL-8) were used as markers of inflammation. Endometrial explants were cultured from uteri collected from follicular phase mares. Explants were challenged with 1 or 10 x 10(...
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...
Prades M, Brown MP, Gronwall R, Houston AE.After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 mic...
Thompson RL, Gunn AJ, Stephen CP, Ip H, Brookes VJ.Uterine luminal pH has been demonstrated to be a valid indicator of uterine health in species such as cattle and sheep. However, research regarding uterine luminal pH in equines is lacking. The objectives of this study were to assess uterine luminal pH in mares during the estrous cycle, and evaluate the effect of dilute vinegar lavage on both uterine luminal pH and endometrial health. The study was conducted using a randomized block design in which eight mares (four Thoroughbred and four Standardbred) were aged matched then randomly assigned to two groups. Endometrial biopsies were taken from ...
Welter H, Bollwein H, Weber F, Rohr S, Einspanier R.The expression of the endothelial and inducible nitric oxide synthases (eNOS and iNOS, respectively) was examined in the endometrium of cyclic and pregnant mares by real-time polymerase chain reaction and immunohistology. The concentration of eNOS mRNA varied throughout the oestrous cycle, with significantly higher transcripts on Day 5 of the oestrous cycle (P 0.05). In early pregnant mares both eNOS and iNOS mRNA increased between Days 12 and 15 (P < 0.05). In cyclic mares, eNOS protein was detected immunocytochemically in endometrial epithelia, the basement membrane, the endothelial laye...
Ganjam VK, McLeod C, Klesius PH, Washburn SM, Kwapien R, Brown B, Fazeli MH.The reaction between ovarian hormones and experimental uterine infection (Streptococcus zooepidemicus) was investigated in 3 groups, each containing 6 ovariectomized mares. Group 1 served as controls ('anoestrus'), Group 2 mares were injected with oestrogen ('oestrus') and Group 3 with progesterone ('dioestrus') over a period of 5 weeks. All mares received an intrauterine inoculation of the bacteria 1 week after the start of hormonal treatment, and the results of the challenge were examined by endometrial biopsy and swabs once weekly. At the end of Week 1 no bacteria were recovered from the ma...
Walter I, Klein M, Handler J, Aurich JE, Reifinger M, Aurich C.To evaluate changes of glycoconjugate in uterine glands of endometrial tissues obtained from mares. Methods: adult mares. Methods: Uterine biopsy samples were collected during the breeding season and analyzed histologically for signs of chronic endometrial degeneration. Stage of the estrous cycle was established, using clinical examination and determination of hormonal status. Uterine tissue samples were analyzed, using lectin histochemical and immunohistochemical techniques (estrogen and progesterone receptors). Connective tissues were stained to determine alterations of ground substance in p...
Scott CJ, de Mestre AM, Verheyen KL, Arango-Sabogal JC.The overall aim of this work was to identify the potential impact of misclassification errors associated with routine screening and diagnostic testing for endometritis in mares. Using Bayesian latent class models (BLCM), specific objectives were to: 1) estimate the diagnostic accuracy of cytology and culture of endometrial swab samples to detect endometritis in mares; 2) assess the impact of different cytology thresholds on test accuracy and misclassification costs; and 3) assess the sensitivity (Se) and specificity (Sp) of a diagnostic strategy including both tests interpreted in series and p...
Duval LH, Rechsteiner SMF, Gastal GDA, Gastal MO, Mattos RC, Gastal EL.After having been brought to America 400 years ago, the Criollo horse reproduced freely for centuries in the southern part of the American continent. Roughness, resistance, and endurance are typical characteristics of this breed of horses. Although the natural selection that occurred over the centuries may have positively influenced the fertility and longevity of this breed, information regarding ovarian function and other reproductive aspects of Criollo breed mares under natural or controlled management conditions is scarce. The objectives of the present study were to (1) characterize the fol...
Monteiro de Barros MR, Davies-Morel MCG, Mur LAJ, Creevey CJ, Alison RH, Nash DM.Persistent mating-induced endometritis is a major cause of poor fertility rates in the mare. Endometritis can be investigated using an ex vivo equine endometrial explant system which measures uterine inflammation using prostaglandin F2α as a biomarker. However, this model has yet to undergo a wide-ranging assessment through transcriptomics. In this study, we assessed the transcriptomes of cultured endometrial explants and the optimal temporal window for their use. Endometrium harvested immediately post-mortem from native pony mares (n = 8) were sampled (0 h) and tissue explants were cultured ...
Camacho Benítez A, Vasconcellos R, Lombide P, Viotti H, Pérez W, Cazales N, Cavestany D, Martin GB, Pedrana G.Heat shock proteins play a crucial role in cellular development, proliferation, differentiation and apoptosis. Heat shock protein 90 (HSP90) has been localised in the human endometrium, where its immunoexpression changes during the menstrual cycle. Similar studies have not been done for the equid species, so the present study aimed to describe endometrial HSP90 immunoexpression in mare endometrium. Endometrial biopsies were formalin-fixed and paraffin-embedded, and sections were stained with haematoxylin-eosin in preparation for HSP90 immunohistochemistry. Immunostaining and morphometric analy...
Grimm AL, Schoon HA, Schöniger S.Equine endometritis eosinophilica (EE) is rarely described and its diagnostic criteria are not defined. The aim of this study was to characterize histological features of EE. A data base (1995-2013) was searched for biopsies with increased eosinophils. This study included all biopsies with this diagnosis and representative biopsies without this record. The definition of equine EE was based on criteria for EE in women and the results of the determination of physiological numbers of eosinophils within the equine endometrium. EE was diagnosed in 55 mares. Biopsies of 10 mares contained eosinophil...
