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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.
Reproductive stage and sex steroid hormone levels influence the expression of mesenchymal stromal cell (MSC) markers in the equine endometrium. Mesenchymal stem or stromal cells (MSCs) play key roles in tissue homeostasis. In the cyclic equine endometrium, this may be regulated by changes in serum concentrations of sex steroid hormones. This study was designed to investigate the changes in endometrial expression of MSC markers during reproductive cycles in mares and the influence of sex steroid hormones on endometrial MSC proliferation in vitro. Endometrial biopsies were collected from pony mares at different reproductive stages (estrus; day 5 and 13 after ovulation; seasonal anestrus; 20 h and 7days post-partum; n = 5 per stag...
Endometrial nitric oxide synthase activity in mares susceptible or resistant to persistent breeding-induced endometritis and the effect of a specific iNOS inhibitor in vitro. Emerging research suggests that the nitric oxide system may play a role in persistent breeding-induced endometritis (PBIE) in the mare. Differences in uterine nitric oxide (NO) levels between mares susceptible or resistant to PBIE and a dose-dependent inhibitory effect of NO on uterine contractility have been demonstrated. The objectives of this study were to investigate the difference in total nitric oxide synthase (NOS) activity of the endometrium between susceptible and resistant mares and the effect of a specific inducible nitric oxide synthase (iNOS) inhibitor on the endometrial NOS activ...
Expression of indoleamine 2,3-dioxygenase 1 as transcript and protein in the healthy and diseased equine endometrium. The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) acts immunomodulatory and restricts bacterial growth. In the uterus of women and mice, it likely contributes to tissue homeostasis and disease pathogenesis. Pregnancy failure in mares is often caused by endometritis and endometrosis. The pathogenesis of nonsuppurative endometritis and endometrosis is still uncertain. To the authors' knowledge, no information on IDO1 expression in the equine endometrium is published. Aim of this study was to examine the presence of IDO1 as transcripts and proteins in the healthy and diseased endometrium of 25 mare...
Constituents of neutrophil extracellular traps induce in vitro collagen formation in mare endometrium. Neutrophil extracellular traps (NETs) are DNA complexes carrying nuclear and cytoplasmic proteins, such as elastase (ELA), cathepsin-G (CAT) and myeloperoxidase (MPO). Mare endometrosis is a chronic degenerative process characterized by excessive collagen in endometrium. While NETs fight bacteria that cause endometritis, they may trigger endometrial fibrogenesis. The aim was to evaluate the in vitro effect of some NETs components on mare endometrial fibrogenesis and determine its relationship with histopathology or estrous cycle. Endometrial explants were incubated with NETs components (ELA, ...
Evaluating the electrical impedance and mucus-related gene expression of uterine endometrial tissues in mares. We investigated the electrical impedance of the reproductive tracts (vagina and uterine endometrial tissues) and the expression of mucus-related genes to identify the stage of the estrous cycle in mares. We first examined vaginal impedance in native Hokkaido mares during their estrous cycle and found no significant differences. However, impedance levels tended to decrease towards ovulation. Furthermore, we investigated the estrous cycle by measuring the electrical impedance of the uterine endometrial tissues obtained from carcasses of mares. We found that impedance levels in the endometrial ti...
Comparative histomorphological study of endometrium in mares. Uterine acute post-breeding inflammation is a physiological tissue response to the entry of exogenous elements, with persistent endometritis being the main pathology responsible for subfertility in the mare (Equus ferus caballus; Linnaeus, 1758). Mares can be classified as susceptible or resistant to endometritis according to their ability to remove intrauterine fluid within 48 hr after experimental inoculation. Endometrial biopsy is a technique that is commonly used to establish the degree of lesions that can affect the fertility of the mare. Endometrial histomorphometry is an objective and ...
Effect of side of the corpus luteum and pregnancy on estrogen and progesterone receptor expression and localization in the endometrium of mares. The effect of side of corpus luteum on uterine gene expression and protein localization of estrogen receptor α (ERα) and progesterone receptor (PR) in healthy cyclic and pregnant mares 13 days after ovulation (day 0) was investigated. Transcervical biopsies were performed to collect endometrium ipsilateral and contralateral regarding the side of corpus luteum on day 13 post-ovulation in cyclic (n = 6) and pregnant (n = 6) mares. Blood samples were collected daily from day 0 until the day of biopsy for 17β-estradiol (E2) and progesterone (P4) determinations. Receptor expression was d...
Endometrial expression of estrogen and progesterone receptors in non-cyclic mares treated only with long-acting progesterone. Administration of progesterone (P4) after estradiol is usually performed to prepare non-cyclic mares as embryo recipients. However, there are successful pregnancy reports after embryo transfer in non-cyclic mares treated only with progestins. The objective of this study was to evaluate endometrial gene expression and immunostaining for estrogen receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in seasonal anestrous mares treated with long acting P4 (LA P4). Endometrial tissue from eight seasonal anestrous mares was collected immediately before administration of 1.5 g of LA P4 ...
Effects of body condition score (BCS) on steroid- and eicosanoid-metabolizing enzyme activity in various mare tissues during winter anoestrus. The objective of this study was to determine the activity of steroid- and eicosanoid-metabolizing enzymes in horses with varying BCSs. The BCSs of twenty non-pregnant, anoestrous mares were determined prior to euthanasia, and tissue samples were collected from the liver, kidney, adrenal gland, ovary and endometrium. Cytochrome P450 1A (CYP1A), 2C (CYP2C), 3A (CYP3A) and uridine 5'-diphospho-glucuronosyltransferase (UGT) activities were determined using luminogenic substrates. The MIXED procedure of SAS was used to test the effect of BCS on enzyme activity and differences between tissues. Activ...
Streptococcus equi subsp. zooepidemicus Invades and Survives in Epithelial Cells. subsp. () is an opportunistic pathogen of several species including humans. is found on mucus membranes of healthy horses, but can cause acute and chronic endometritis. Recently was found able to reside in the endometrium for prolonged periods of time. Thus, we hypothesized that an intracellular phase may be part of the pathogenesis and investigated if was able to invade and survive inside epithelial cells. HEp-2 and HeLa cell lines were co-cultured with two strains (1-4a and S31A1) both originating from the uterus of mares suffering from endometritis. Cells were fixed at different time...
Equine Endometrial Explants Undergo Significant Degenerative Changes in Culture. This study evaluated equine endometrial explants following 12, 24, and 48 hr in culture. Measurement of an indicator of cell death in explant supernatant, light microscopy, and gene expression of biomarkers of endometrial function and cellular stress were used to compare the effect of six different media on explant viability and morphology. Viability of explants was assessed indirectly through measuring LDH activity in the culture supernatant. Regardless of culture medium composition, a significant increase in LDH activity was observed within 12 hr of culture, indicating occurrence of cell dam...
Reliability of histopathological examination and immunohistochemistry of a single biopsy for evaluation of endometrial health in Icelandic mares. Endometritis and endometrosis have been and still are the major reasons for infertility in mares. The diagnosis of endometritis can be based on cytology and microbiology, but endometrial biopsy is still the only way to diagnose endometrosis in the mare. Our study attempted to determine if a single biopsy using his-topathology and immunohistochemistry is sufficient to ascertain reasons for infertility in Icelandic mares. The objectives of this study were to examine the relationship between deviations in endometrial biopsies in terms of prostaglandin-endoperoxide synthase-2 (PTGS-2) and fibronec...
Equine mesenchymal stem cells derived from endometrial or adipose tissue share significant biological properties, but have distinctive pattern of surface markers and migration. 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, ...
Likelihood of pregnancy after embryo transfer is reduced in recipient mares with a short preceding oestrus. Previous surveys reported a positive association between the length of the follicular phase and subsequent fertility in embryo transfer donor and Thoroughbred mares. However, it is unclear whether a longer oestrus positively influences fertilisation and oviductal development (oocyte quality, oviductal environment), or uterine receptivity and survival of the embryo in the uterus. Objective: To determine the effect of length of oestrus (characterised by duration of endometrial oedema) on likelihood of pregnancy and early embryo loss (EEL) in recipient mares after embryo transfer (ET). Methods: R...
Milk-fat globule epidermal growth factor 8 (MFGE8) is expressed at the embryo- and fetal-maternal interface in equine pregnancy. Milk-fat globule epidermal growth factor (EGF) 8 protein (MFGE8), also known as lactadherin, promotes cell adhesion in an Arg-Gly-Asp (RGD)-dependent modus via integrins. In the present study, the expression of MFGE8 was examined in equine endometrium during oestrus and at Days 12 and 16 after ovulation in pregnant and non-pregnant mares and in mares during the 5th month of gestation. Results demonstrated that MFGE8 is expressed at the embryo- and fetal-maternal interface in equine pregnancy. In non-pregnant endometrium its expression was upregulated by oestrogen, a finding that was confirmed ...
Uterine clinical findings, fertility rate, leucocyte migration, and COX-2 protein levels in the endometrial tissue of susceptible mares treated with platelet-rich plasma before and after AI. Persistent mating-induced endometritis (PMIE) results in decreased fertility in horses, thereby causing a significant impact in the horse market. Platelet-rich plasma (PRP), a modulator of the inflammatory response, has been largely used in veterinary medicine. Here, we investigated the effects of PRP on uterine inflammation, conception rate, endometrial polymorphonuclear neutrophil (PMN) migration, and COX-2 protein levels in the endometrial tissue. Thirteen PMIE-susceptible mares were used for artificial insemination (AI). The mares were inseminated with fresh semen in three consecutive cycl...
The effects of intrauterine infusion of peanut oil on endometrial health, salivary cortisol and interovulatory period in mares. Intrauterine infusion of peanut oil at Day 10 post-ovulation has been reported to prolong dioestrus in mares. However, the effects of peanut oil treatment on the endometrium and whether the technique is painful have not been assessed. The objectives of this study were, (i) to determine the effect of intrauterine infusion of peanut oil on endometrial health, (ii) to determine whether use of intrauterine peanut oil is painful and (iii) to confirm that peanut oil causes prolonged dioestrus. Six mares aged 3-12 years old were used in a cross-over design with each mare administered both 1 ml of in...
Seasonal or pathological findings? Morphofunctional characteristics of the equine endometrium during the autumn and spring transition. The deep anoestrous phase in winter is part of the anovulatory season in mares and is bordered by the autumn and spring transitional periods (ATP/STP). To define an annual time span for effective prognostic biopsy sampling, the aim of this study was to provide a morphofunctional characterization of the endometrium during ATP and STP. To outline both transitional periods, endometrial specimens were taken in September, October and November (n = 76) as well as February, March and April (n = 184) with the requirement of a detailed clinical documentation. Tissue samples were examined histologic...
Administration of 2.5 mg of estradiol followed by 1,500 mg of progesterone to anovulatory mares promote similar uterine morphology, hormone concentrations and molecular dynamics to those observed in cyclic mares. To test the hypothesis that the administration of 2.5 mg of estradiol benzoate (EB) followed by 1500 mg of long acting progesterone (LA P4) causes similar uterine changes and molecular dynamics in anovulatory mares to those observed in cyclic ones, we evaluated the changes of estrogen (ERα and ERβ) and progesterone receptors (PR) in anestrous, transitional and cyclic mares by RT-qPCR and immunohistochemistry. In addition, we evaluated uterine edema, tonus and estrogens and progesterone plasma profile. Endometrial biopsies were taken from anestrous and transitional mares immediately before ...
Expression of Toll-like receptors 2, 4 and 6 in different cell populations of the equine endometrium. Subfertility in mares is mainly caused by endometrial diseases. Alterations of Toll-like receptors (TLRs) are associated with endometrial disorders in women. This study investigated TLRs 2, 4 and 6 in the equine endometrium. Endometria of 21 mares were examined by histology, PCR and immunohistochemistry. Tissues from 2 mares were considered normal. The remaining showed endometritis, endometrosis and/or angiosclerosis. TLRs 2, 4 and 6 were expressed as transcripts and proteins in all endometria. Immunohistochemistry detected TLRs 2, 4 and 6 in mast cells, luminal and glandular epithelial cells,...
Histopathological features of endometritis eosinophilica in mares. 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...
Expression of Toll-like receptors 2, 4 and 6 in equine endometrial epithelial cells: A comparative in situ and in vitro study. Endometrial epithelial cells form a luminal barrier and are exposed to pathogens and non-infectious antigens. Toll-like receptors (TLRs) mediate pathogen defenses and tissue homeostasis, but are also involved in the pathogenesis of inflammatory and fibrosing alterations. Endometrial diseases are important causes of subfertility in mares. The pathogenesis of some types of persistent inflammation and periglandular fibrosis (endometrosis) is unknown. The aim of this study was to compare by in situ and in vitro immunohistochemistry the expression of TLRs 2, 4 and 6 in equine endometrial epithelial...
Hexokinase 2 drives glycogen accumulation in equine endometrium at day 12 of diestrus and pregnancy. Secretion of histotroph during the prolonged pre-implantation phase in mares is crucial to pregnancy maintenance, manifested as increased embryonic loss in mares with age-related endometrial degeneration. Glycogen content of uterine histotroph is higher during the progesterone-dominated phase of the estrous cycle in mares, but regulatory mechanisms are not well understood. Methods: mRNA expression of glycogen-metabolizing enzymes (HK1, HK2, GSK3B, GYS1, PEPCK, PKM, PYGM) in endometrial samples were compared among mares in anestrus, estrus, and at Day 12 of diestrus and pregnancy. In addition, ...
Localisation of epidermal growth factor (EGF), its specific receptor (EGF-R) and aromatase at the materno-fetal interface during placentation in the pregnant mare. Implantation and placentation in the mare does not commence until as late as day 40 after ovulation. The reasons for this and the growth factors and/or hormones which drive placentation when it does finally occur are of considerable academic and practical interest. Placental interface tissues recovered from 11 accurately aged and perfused-fixed horse uteri between 20 and 68 days of gestation were stained immunocytochemically for Epidermal Growth Factor (EGF), its specific receptor (EGF-R) and for the steroid hormone enzyme, aromatase. EGF was present in endometrial gland and lumenal epithelia ...
Expression of uterine lipocalin 2 and its receptor during early- to mid-pregnancy period in mares. From previous cDNA subtraction studies analyzing gene expression in equine endometrium, high lipocalin 2 (LCN2) mRNA expression was found in the gravid endometrium. In the uterus, LCN2 may transport hydrophobic molecules and siderophores with iron, or may form a complex with another protein, however, the expression of uterine LCN2 beyond day 20 of equine pregnancy and its receptor has not been characterized. To study the expression and potential roles of uterine LCN2 from pre-implantation to mid-gestation period, stage-specific endometrial samples were obtained from day 13 (day 0 = ovulation) ...
Preattachment Embryos of Domestic Animals: Insights into Development and Paracrine Secretions. In mammalian species, endometrial receptivity is driven by maternal factors independently of embryo signals. When pregnancy initiates, paracrine secretions of the preattachment embryo are essential both for maternal recognition and endometrium preparation for implantation and for coordinating development of embryonic and extraembryonic tissues of the conceptus. This review mainly focuses on domestic large animal species. We first illustrate the major steps of preattachment embryo development, including elongation in bovine, ovine, porcine, and equine species. We next highlight conceptus secret...
Dose-dependent inhibition of uterine contractility by nitric oxide: A potential mechanism underlying persistent breeding-induced endometritis in the mare. Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and...
Oestrous cycle-dependent equine uterine immune response to induced infectious endometritis. Infectious endometritis is a major cause of reduced pregnancy rates in horses. The objectives of this study were to establish a timeline of the innate immune response in the uterus of healthy horses and to investigate the oestrous cycle effect on this. Endometrial biopsies were collected from five horses before and at 3, 12, 24, 48 and 72 h after inoculation of Escherichia coli, once in oestrus and once in dioestrus. They were analysed by quantitative real-time PCR, microbiology and histology. Neutrophil numbers increased from very low levels in the absence of inflammation to severe neutrophi...
Endometritis: Diagnostic Tools for Infectious Endometritis. Infectious endometritis is among the leading causes of subfertility in the mare. However, the best way to reliably diagnose these cases of infectious endometritis can be confusing to the veterinary practitioner. The goal of this article is to describe how to perform various sample collection techniques, what analyses can be performed on these samples, and how to interpret the results of these analysis. Additionally, future technologies will be presented that are not currently used in equine reproduction practice.
Endometritis: Managing Persistent Post-Breeding Endometritis. Endometritis was rated as the third most common medical problem encountered in adult horses in North America. It is the leading cause of subfertility in broodmares and is a major contributor to economic loss in the horse breeding industry, with pregnancy rates reported to be as low as 21% in mares with severe endometritis. Endometritis may be categorized as: endometrosis (chronic degenerative endometritis), acute, chronic, active, dormant, subclinical, clinical, and persistent post-breeding. These classifications are not mutually exclusive, and mares may change categories within breeding seaso...
