Prostaglandins are lipid compounds derived from fatty acids that are present in various tissues of horses. They are involved in a wide range of physiological processes, including the regulation of inflammation, blood flow, and reproductive functions. In equine medicine, prostaglandins are often studied for their role in modulating inflammatory responses and their potential therapeutic applications. These compounds can influence pain perception and are involved in processes such as parturition and the estrous cycle in mares. This page collects peer-reviewed research studies and scholarly articles that explore the synthesis, function, and clinical applications of prostaglandins in equine health.
Jaworska J, Ropka-Molik K, Kowalczyk-Zięba I, Boruszewska D, Wocławek-Potocka I, Siemieniuch M.Physiological parturition is characterized by sterile, inflammatory-like processes. During parturition, the placenta expresses various proinflammatory mediators, such as chemokines and IL-17. Nevertheless, inflammatory processes present in the parturient mare are poorly characterized. The aim of this study was to investigate the expression of selected chemokines and IL-17 in the allantochorion and the endometrium of mares that retained fetal membranes (RFM) and expelled them physiologically. We hypothesized that the expression of these mediators may be altered in the placenta of mares with RFM...
Szóstek-Mioduchowska A, Leciejewska N, Zelmańska B, Staszkiewicz-Chodor J, Ferreira-Dias G, Skarzynski D.Equine endometrosis is a chronic degenerative condition, described as endometrial fibrosis that forms in the stroma, under the basement membrane and around the endometrial glands. The role of lysophosphatidic acid (LPA) in the development of tissue fibrosis varies depending on the organ, and its profibrotic role in mare endometrosis remains unclear. The study aimed to establish the endometrial presence of LPA and its receptors (LPAR1-4), together with its effects on connective tissue growth factor (CTGF) and prostaglandins (PG) secretion from equine endometrium under physiological (estrous cyc...
Mançanares ACF, Cabezas J, Manríquez J, de Oliveira VC, Wong Alvaro YS, Rojas D, Navarrete Aguirre F, Rodriguez-Alvarez L, Castro FO.In mesenchymal stem cells (MSCs), it has been reported that prostaglandin E2 (PGE2) stimulation of EP2 and EP4 receptors triggers processes such as migration, self-renewal, survival, and proliferation, and their activation is involved in homing. The aim of this work was to establish a genetically modified adipose (aMSC) model in which receptor genes EP2 and EP4 were edited separately using the CRISPR/Cas9 system. After edition, the genes were evaluated as to if the expression of MSC surface markers was affected, as well as the migration capacity in vitro of the generated cells. Adipose MSCs we...
Lilliehöök I, Bröjer J, Nostell K, Kindahl H, Tvedten HW, Edner A, Hagman R.Endotoxemia is a common and severe disease of horses. Most previous studies have monitored changes caused by a bolus dose of endotoxin over short time periods. Objective: We aimed to describe inflammatory responses to endotoxin with inflammatory and hematologic markers monitored over a longer time than has been performed in the past using more prolonged endotoxin exposures. Methods: Escherichia coli O55:B5 endotoxin was administered as a 6-hour continuous intravenous infusion of lipopolysaccharide (LPS) to eight horses. Blood cell counts, and prostaglandin F -metabolite (PGM), serum amyloid A ...
Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B, Morán G, Plaza A, Henríquez C.Mesenchymal stem/stromal cells (MSCs) are increasingly explored for the treatment of degenerative and inflammatory diseases in human and veterinary medicine. One of the key characteristics of MSCs is that they modulate inflammation mainly through the secretion of soluble mediators. However, despite widespread clinical use, knowledge regarding the effector mechanisms of equine MSCs, and consequently their effectiveness in the treatment of diseases, is still unknown. The objectives of this study were to determine the mechanisms underlying inhibition of lymphocyte proliferation by equine bone mar...
Oliveira SN, Segabinazzi LGTM, Canuto L, Lisboa FP, Medrado FE, Dell'Aqua JA, Aguiar AJA, Papa FO.The goal of this study was to compare the efficiency of histrelin acetate (GnRH analog) and human chorionic gonadotropin (hCG) to hasten ovulation in Brazilian Northeastern jennies (Equus africanus asinus). Thirty cycles of ten jennies were randomly assigned in one of the three groups: G0 (control group), saline; G1, 250 μg of histrelin acetate; G2, 2500 IU of hCG. Jennies were evaluated by transrectal palpation and ultrasonography, and had the administration of an ovulation-inducing agent when a follicle measuring between 29 and 32 mm of diameter was diagnosed. Jennies were monitored every...
Szóstek-Mioduchowska AZ, Baclawska A, Rebordão MR, Ferreira-Dias G, Skarzynski DJ.An increasing number of studies have shown that prostaglandins (PGs) exert multiple regulatory actions in the processes associated to tissue remodeling and fibrosis. Extracellular matrix (ECM) turnover is mediated by matrix metallopeptidases (MMPs). The knowledge about the regulation of their expression in mare endometrium is still limited. Thus, the aim of this study was to investigate whether: (i) profibrotic transforming growth factor (TGF)-β1 modulates PG production in equine endometrium; and (ii) PGE and PGF modulate MMPs, their tissue inhibitors (TIMPs), and collagen 1 (COL1) expression...
Piotrowska-Tomala KK, Jonczyk AW, Skarzynski DJ, Szóstek-Mioduchowska AZ.Prostaglandins (PGs) play crucial roles in the regulation of the oestrus cycle and establishment of pregnancy in animals. Luteinizing hormone (LH) and ovarian steroids are involved in regulating endometrial PG production in many species. Their effects on PG production and associated pathways in the mare myometrium and endometrium are the subjects of our interest. This study aimed to evaluate the specific effects of LH and ovarian steroids on equine myometrial and endometrial tissues on (i) PGE and PGF secretion and (ii) transcription of genes encoding specific enzymes responsible for PG synthe...
Sotelo EDP, Vendruscolo CP, Fülber J, Seidel SRT, Jaramillo FM, Agreste FR, Silva LCLCD, Baccarin RYA.Several studies in human and equine medicine have produced controversial results regarding the role of dimethylsulfoxide (DMSO) as a therapeutic agent. This study aimed to evaluate the effect of joint lavage with different DMSO concentrations on biomarkers of synovial fluid inflammation and cartilage degradation in joints with lipopolysaccharide (LPS)-induced synovitis. Twenty-six tibiotarsal joints of 13 horses were randomly distributed into four groups (lactated Ringer's solution; 5% DMSO in lactated Ringer's; 10% DMSO in lactated Ringer's; and sham). All animals were evaluated for the prese...
Cox S, Sommardahl C, Fortner C, Davis R, Bergman J, Doherty T.Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma. M...
Knych HK, Arthur RM, McKemie DS, Baden RW, Seminoff K, Kass PH.Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects. Objective: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. M...
Petrucci L, Maranesi M, Verini Supplizi A, Dall'Aglio C, Mandara MT, Quassinti L, Bramucci M, Miano A, Gobbetti A, Catone G, Boiti C, Zerani M.The objectives of this study were to evaluate in horse testes the expression of kisspeptin (KiSS) and GnRH1 neuropeptides and their cognate receptors, KiSS1R and GnRH1R, as well as their action on testosterone, GnRH1, prostaglandin F2α (PGF2α), and PGE2 synthesis and cyclooxygenase 1 (COX1) and COX2 activity by Leydig cells in vitro. Testes were obtained from 9 sexually mature horses by surgical castration. Immunohistochemistry, evidenced the presence of KiSS, KiSS1R, GnRH, and GnRH1R in Leydig cells, whereas germinal and Sertoli cells were positive only for GnRH1. Transcripts for both neur...
Tarko A, Fabová Z, Kotwica J, Valocký I, Alrezaki A, Alwasel S, Harrath AH, Sirotkin AV.The influence of environmental contaminant toluene and of plant fennel (Foeniculum vulgare Mill.) on reproduction are reported, but the mechanisms of their action and the protective effect of fennel on contaminant influence remain to be elucidated. In this study, we hypothesized that toluene and fennel directly affects basic ovarian cell functions, and that fennel can be used as an appropriate natural protective agent against the potential adverse effects of toluene. This study aimed to examine the action of toluene (20 μg/mL) and fennel extract (0, 1, 10, 100 μg/mL), and assess their comb...
Rapacz-Leonard A, Leonard M, Chmielewska-Krzesińska M, Siemieniuch M, Janowski TE.Despite their importance in mammalian reproduction, substances in the oxytocin-prostaglandins pathways have not been investigated in the horse placenta during most of pregnancy and parturition. Therefore, we quantified placental content of oxytocin (OXT), oxytocin receptor (OXTR), and prostaglandin E2 and F2 alpha during days 90-240 of pregnancy (PREG), physiological parturition (PHYS), and parturition with fetal membrane retention (FMR) in heavy draft horses (PREG = 13, PHYS = 11, FMR = 10). We also quantified OXTR and prostaglandin endoperoxide synthase-2 (PTGS2) mRNA expression ...
Delco ML, Goodale M, Talts JF, Pownder SL, Koff MF, Miller AD, Nixon B, Bonassar LJ, Lundgren-Åkerlund E, Fortier LA.Early intervention with mesenchymal stem cells (MSCs) after articular trauma has the potential to limit progression of focal lesions and prevent ongoing cartilage degeneration by modulating the joint environment and/or contributing to repair. Integrin α10β1 is the main collagen type II binding receptor on chondrocytes, and MSCs that are selected for high expression of the α10 subunit have improved chondrogenic potential. The ability of α10β1-selected (integrin α10high) MSCs to protect cartilage after injury has not been investigated. To investigate integrin α10high MSCs to prevent postt...
Millican AA, Leatherwood JL, Coverdale JA, Arnold CE, Bradbery AN, Larson CK, Lamprecht ED, White SH, Paulk CB, Welsh TH, Wickersham TA.Sixteen weanling Quarter Horses (255 ± 22 kg) were utilized in a 56-d trial to evaluate the effects of trace mineral (TM) source on intra-articular inflammation following a single acute inflammatory insult. Horses were stratified by age, sex, and BW and then randomly assigned to dietary treatment: concentrate formulated with Zn, Mn, Cu, and Co as inorganic sources (CON; n = 8) or complexed TMs (CTM; n = 8). Added TM were formulated at iso-levels across treatments and intakes met or exceeded NRC requirements. Horses were offered 1.75% BW (as-fed) of treatment concentrate and 0.75% BW (as-fed) ...
Brunner TJ, Lescun TB, Moore GE, Grady SE, Davern AJ, Taylor SD.The mechanism by which nonsteroidal anti-inflammatory drugs mitigate pain caused by a heart bar shoe (HBS) model of lameness is unknown. The purpose of this study was to determine if this HBS model of lameness induces inflammation in horses. Five healthy adult horses from a university teaching herd were enrolled. A custom HBS was applied to the left front foot of each horse, followed by induction of the American Association of Equine Practitioners Lameness Score of 4. Inflammatory markers including serum amyloid A (SAA) concentration, local venous tumor necrosis factor alpha and prostaglandin ...
Neuenschwander HM, Moreira JJ, Vendruscolo CP, Fülber J, Seidel SRT, Michelacci YM, Baccarin RYA.The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treat...
Fernandes CB, Ball BA, Loux SC, Boakari YL, Scoggin KE, El-Sheikh Ali H, Cogliati B, Esteller-Vico A.Anatomical and molecular changes in the cervical barrier in women are a fundamental part of the pathogenesis of pregnancy loss associated with chorioamnionitis. However, there is little information regarding changes in the cervix associated with ascending infection in pregnant mares. To better characterize morphological and molecular changes in the cervix during placentitis, we examined full thickness histology and mRNA expression for a number of inflammatory and endocrine factors in the mucosa and stroma of the cervix of mares (n = 5) after experimental induction of placentitis via transc...
Klohonatz KM, Coleman SJ, Islas-Trejo AD, Medrano JF, Hess AM, Kalbfleisch T, Thomas MG, Bouma GJ, Bruemmer JE.Equine maternal recognition of pregnancy (MRP) is a process whose signal remains unknown. During MRP the conceptus and endometrium communicate to attenuate prostaglandin F (PGF) secretion, sparing the corpus luteum and maintaining progesterone production. Recognition of a mobile conceptus by the endometrium is critical by days 14-16 post-ovulation (PO), when endometrium produces PGF, initiating luteolysis. The objective of this study was to evaluate endometrial gene expression changes based upon pregnancy status via RNA sequencing. This experiment utilized a cross-over design with each mare se...
Podico G, Canisso IF, Ellerbrock RE, Dias NW, Mercadante VRG, Lima FS.The present study aimed to compare two methods of prostaglandin-induced abortion in mares by determining blood markers (progesterone, estradiol-17β, alpha-fetoprotein, 13,14-dihydro-15-keto-prostaglandin-F2α (PGFM)), B-mode ultrasonographic parameters, and time until loss of fetal heartbeat. It was hypothesized that intrauterine infusion of cloprostenol results in earlier fetal compromise than intramuscular administration. Ovarian structures (number and sizes of follicles and corpora lutea area), fetal heartbeat, and fetal mobility of thirteen singleton pregnancies were assessed daily by tra...
Grzanna MW, Au RY, Au AY, Rashmir AM, Frondoza CG.Tendinopathy, a common disorder in man and horses, is characterized by pain, dysfunction, and tendon degeneration. Inflammation plays a key role in the pathogenesis of tendinopathy. Tendon cells produce proinflammatory molecules that induce pain and tissue deterioration. Currently used nonsteroidal anti-inflammatory drugs are palliative but have been associated with adverse side effects prompting the search for safe, alternative compounds. This study determined whether tendon-derived cells' expression of proinflammatory cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE) could be a...
Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL.Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuc...
Martínez-Boví R, Zagrajczuk A, Donadeu FX, Skarzynski DJ, Piotrowska-Tomala K, Cuervo-Arango J.Haemorrhagic anovulatory follicles (HAFs) are the most common pathological anovulatory condition in the mare. To enhance understanding of the physiopathology of HAFs, the aim of the present study was to determine the effects of an induced-follicular wave on LH concentrations and follicular fluid factors relevant to the ovulatory process. Mares were allocated to treatment or control groups (n = 7/group) in a crossed over design during 14 oestrous cycles with a period of one cycle occurring when there were no treatments between the times when treatments were administered. In the treatment gr...
Machado TSL, Massoco CO, Silva LCLC, Fülber J, Moreira JJ, Baccarin RYA.To compare effects of platelet-rich plasma (PRP), interleukin-1 receptor antagonist protein (IRAP), autologous processed plasma (APP), and sodium hyaluronate treatments on synovial fluid cells in vitro and on synovial fluid obtained from osteochondrotic joints of horses. Methods: Synovial fluid cells from 8 healthy equine tibiotarsal joints (in vitro experiment) and synovial fluid samples from 40 tibiotarsal joints of 25 horses with osteochondrosis dissecans (in vivo experiment). Methods: Effects of various treatments on concentrations of prostaglandin (PG) E2, interleukin (IL)-1β, tumor necr...
Pietrani M, Losinno L, Cuervo Arango J.In the present study, 2.228 cycles of 180 Polo Argentino donor mares from an embryo transfer program in Argentina were examined to evaluate the effects of: (1) Interval from Prostaglandin F2alpha analog treatment to ovulation (ITO) on embryo recovery rate (ERR); (2) ITO on number of embryos per flushing (EPF); (3) ITO on multiple ovulation (MO) rate; (4) ITO from donor mare on pregnancy rate (PR) in recipient mares. Mares were inseminated with fresh semen from 31 fertile stallions in the induced estrus. Embryo flushing was performed 7-8 days postovulation. Following embryo flushing, donor mar...
Ginther OJ, Domingues RR, Kennedy VC, Dangudubiyyam SV.An inhibitor of PGF2α biosynthesis (flunixin meglumine, FM) was used to study the role of endogenous PGF2α on the luteolytic effect of exogenous PGF2α in mares. A 2-h infusion of PGF2α at a constant rate (total dose, 0.1 mg) on Day 10 (ovulation = Day 0) was used to mimic the maximal concentrations of a spontaneous pulse of a PGF2α metabolite (PGFM). Treatment with FM (1.7 mg/kg) was done 1 h before and 5 h after the start of PGF2α infusion. In hourly blood samples beginning 1 h before the start of PGF2α infusion, progesterone decreased (P < 0.05) similarly by 5 h in each of t...
Thompson DL, Valencia NA, Walker NL, Oberhaus EL.Five experiments were performed to test the hypothesis that α-melanocyte-stimulating hormone (MSH) is secreted in response to various stressors in horses similar to prolactin, growth hormone, and adrenocorticotropin (ACTH). There was considerable variation in resting concentrations of MSH and in the degree of stimulation in responders; thus all data sets were tested for heterogeneity of variance and corrected for as needed before analysis. In experiment 1, 12 mares were used in a switchback design to test the effect of a 2-minute exercise bout on MSH secretion. Plasma MSH concentrations were ...
Klohonatz KM, Nulton LC, Hess AM, Bouma GJ, Bruemmer JE.Maternal recognition of pregnancy (MRP) in the mare is an unknown process. In a non-pregnant mare on day 14 post-ovulation (PO), prostaglandin F2α (PGF) is secreted by the endometrium causing regression of the corpus luteum. Prior to day 14, MRP must occur in order to attenuate secretion of PGF. The embryo is mobile throughout the uterus due to uterine contractions from day of entry to day 14. It is unknown what signaling is occurring. Literature stated that infusing oil or placing a glass marble into the equine uterus prolongs luteal lifespan and that in non-pregnant mares, serum exosomes co...
Siemieniuch MJ, Kozdrowski R, Szóstek-Mioduchowska AZ, Raś A, Nowak M.Endometritis is one of the most important causes of infertility in mares. Mares may suffer from endometritis outside the breeding season; however, pathological condition is often undiagnosed in anestrus. The aim of this study was to examine whether the secretion profiles of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), and a metabolite of prostacyclin I2 (6-keto-PGF1α) differ in endometrial tissue cultures of heavy draft mares in anestrus with endometritis compared to those without endometritis. The endometrial biopsies were collected from 51 heavy draft mares. Inclusion criteria for ...
Bazer FW, Vallet JL, Roberts RM, Sharp DC, Thatcher WW.Conceptuses produce steroids, prostaglandins, proteins and possibly other unidentified agents which may play a role in the establishment and maintenance of pregnancy. A key event in this process is protection of the corpus luteum (CL) from the luteolytic activity of prostaglandin (PG) F-2 alpha of uterine origin. Oestrogens produced by the pig conceptuses between Days 11 and 16 appear to exert an antiluteolytic effect resulting in the sequestering of PGF-2 alpha within the uterine lumen. Failure of the pregnant uterus to release PGF-2 alpha in an endocrine fashion, therefore, allows for mainte...
de Ruijter-Villani M, van Tol HT, Stout TA.Endometrial oxytocin receptors (OXTR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are central components of the luteolytic pathway in cyclic mares, and their suppression is thought to be critical to luteal maintenance during early pregnancy. We examined the effect of pregnancy on endometrial expression of potential regulators of prostaglandin (PG) F2α secretion in mares. Expression of the nuclear progesterone receptor and oestrogen receptor ERα was high during oestrus, and depressed when progesterone was elevated; the opposite applied to the membrane progesterone receptor. PTGS2 was up...
Nash DM, Sheldon IM, Herath S, Lane EA.Reproductive efficiency in mares is low and persistent mating-induced endometritis (PMIE) is an important cause of subfertility. Mating-induced endometritis (MIE) an obligate precursor to PMIE, is a ubiquitous, transient inflammatory response to the presence of sperm, seminal components and pathogens. However, the specific inflammatory pathways that derive from MIE and that may also be precursors to PMIE are not clear. The ability to identify and measure robust, repeatable markers of inflammation integral to MIE may be key to understanding the progression to PMIE. The aim of the study was to (...
Belknap JK, Giguère S, Pettigrew A, Cochran AM, Van Eps AW, Pollitt CC.Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure in human sepsis, early inflammatory mechanisms may lead to downstream events resulting in lamellar failure. Characterisation of the type of immune response (i.e. innate vs. adaptive) is essential in order to develop therapeutic strategies to counteract these deleterious events. Objective: To quantitate gene expression of pro-inflammatory cytokines known to be important in the innate and adaptive immune response during the early stages of laminitis, using both the bla...
Aurich C, Budik S.Early equine pregnancy shares many features with that of more intensively assessed domestic animals species, but there are also characteristic differences. Some of those are poorly understood. Descent of the equine conceptus into the uterine lumen occurs at day 5 to 6 after ovulation but is only possible when the embryo secretes prostaglandin E2. Although maintenance of equine pregnancy probably involves secretion of a conceptus derived anti-luteolytic factor, this agent has not been identified. Rapid growth, conceptus mobility and presence of an acellular capsule at the time of maternal recog...
Scaravaggi I, Borel N, Romer R, Imboden I, Ulbrich SE, Zeng S, Bollwein H, Bauersachs S.Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showe...
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...
Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G.Prostaglandin E (PGE) has contradictory effects in many organs. It may have proinflammatory, anti-inflammatory, or anti-fibrotic roles, depending on the type of receptors to which it binds. By signaling through its receptors EP2 and EP4, PGE mediates anti-inflammatory and anti-fibrotic actions. In spite of chronic endometrial fibrosis (endometrosis) being a major cause of mare infertility, its pathogenesis is not fully understood. We have shown that contact of mare endometrium in vitro with neutrophil extracellular traps (NETs) proteases favors endometrial collagen type I production. Therefor...
Moraes AP, Moreira JJ, Brossi PM, Machado TS, Michelacci YM, Baccarin RY.This study aimed to verify whether transient inflammatory reactions incited by the administration of intra-articular platelet-rich plasma (PRP) affected joint components through short- and long-term in vivo evaluation of inflammatory biomarkers and extracellular matrix degradation products in synovial fluid. The effects of PRP were analyzed in a short phase protocol (SPP) and in a prolonged phase protocol (PPP), using saline-injected joints as controls. In the SPP, higher white blood cell counts and prostaglandin E2 and total protein concentrations were observed in the synovial fluid of PRP-tr...
Klohonatz KM, Coleman SJ, Islas-Trejo AD, Medrano JF, Hess AM, Kalbfleisch T, Thomas MG, Bouma GJ, Bruemmer JE.Equine maternal recognition of pregnancy (MRP) is a process whose signal remains unknown. During MRP the conceptus and endometrium communicate to attenuate prostaglandin F (PGF) secretion, sparing the corpus luteum and maintaining progesterone production. Recognition of a mobile conceptus by the endometrium is critical by days 14-16 post-ovulation (PO), when endometrium produces PGF, initiating luteolysis. The objective of this study was to evaluate endometrial gene expression changes based upon pregnancy status via RNA sequencing. This experiment utilized a cross-over design with each mare se...
Orth MW, Peters TL, Hawkins JN.Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Carti...
Galvão A, Henriques S, Pestka D, Lukasik K, Skarzynski D, Mateus LM, Ferreira-Dias GM.We hypothesized that cytokines influence luteal angiogenesis in mares, while angiogenic factors themselves can also regulate luteal secretory capacity. Therefore, the purpose of this study was to evaluate the role of cytokines--tumor necrosis factor alpha (TNF), interferon gamma (IFNG) and Fas ligand (FASL)--on in vitro modulation of angiogenic activity and mRNA level of vascular endothelial growth factor A (VEGF), its receptor VEGFR2, thrombospondin 1 (TSP1), and its receptor CD36 in equine corpus luteum (CL) throughout the luteal phase. After treatment, VEGF protein expression was determined...
Weber JA, Freeman DA, Vanderwall DK, Woods GL.The hypothesis that treatment of pregnant mares with prostaglandin E2 (PGE2) hastens the oviductal transport of equine embryos was tested by treating bred mares with PGE2 on Day 3 after ovulation and subsequently measuring the rate of hastened oviductal transport (estimated by the uterine embryo recovery rate on Day 4 after ovulation). In a preliminary, noncontrolled experiment, oviductal transport was apparently not hastened after intramuscular, intrauterine, or intraperitoneal PGE2 administration to bred mares (0/6, 0/3, and 0/3 mares, respectively). Oviductal transport appeared to be hasten...
Amaral A, Fernandes C, Lukasik K, Szóstek-Mioduchowska A, Baclawska A, Rebordão MR, Aguiar-Silva J, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G.We have shown that bacteria induce neutrophil extracellular traps (NETs) in mare endometrium. Besides killing pathogens, NETs may contribute for endometrosis (chronic endometrium fibrosis). Since elastase (ELA) is a NETs component that regulates fibrosis and prostaglandin (PG) output, the aim was to evaluate if inhibition of ELA would affect collagen 1 (COL1) transcription and PGs secretion by endometrium explants, in different estrous cycle phases. Follicular-FP (n = 8) and mid luteal-MLP (n = 7) phases explants were cultured for 24-48 hr with medium alone (Control), ELA (0.5 μg/ml,1 ...
Tangtrongsup S, Kisiday JD.Dexamethasone is known to support mesenchymal stem cell (MSC) chondrogenesis, although the effects of dose and timing of exposure are not well understood. The objective of this study was to investigate these variables using a laboratory model of MSC chondrogenesis. Methods: Equine MSCs were encapsulated in agarose and cultured in chondrogenic medium with 1 or 100 nM dexamethasone, or without dexamethasone, for 15 days. Samples were analyzed for extracellular matrix (ECM) accumulation, prostaglandin E2 and alkaline phosphatase secretion, and gene expression of selected collagens and catabolic e...
Watson ED, Sertich PL.Embryos, endometrial biopsies, and uterine lavage fluid were collected from pregnant and non-pregnant mares 14 days after ovulation. Embryos were cultured for 20.5 h with and without endometrial tissue from pregnant mares, and endometrial tissue was cultured alone. Endometrial content of PGF tended to be higher (P = 0.06) in non-pregnant than in pregnant mares, but the amount of PGF released from tissue during culture was similar for pregnant and non-pregnant mares. Lavage fluid from non-pregnant mares also tended (P = 0.08) to contain higher concentrations of PGF. Coincubation of embryos with...
Klohonatz KM, Nulton LC, Hess AM, Bouma GJ, Bruemmer JE.Maternal recognition of pregnancy (MRP) in the mare is an unknown process. In a non-pregnant mare on day 14 post-ovulation (PO), prostaglandin F2α (PGF) is secreted by the endometrium causing regression of the corpus luteum. Prior to day 14, MRP must occur in order to attenuate secretion of PGF. The embryo is mobile throughout the uterus due to uterine contractions from day of entry to day 14. It is unknown what signaling is occurring. Literature stated that infusing oil or placing a glass marble into the equine uterus prolongs luteal lifespan and that in non-pregnant mares, serum exosomes co...
Sharp DC, McDowell KJ, Weithenauer J, Thatcher WW.Endometria from pregnant mares are able to produce PGF in vitro, but when co-incubated with conceptus membranes the amount and rate of PGF production is considerably reduced. To estimate the molecular weight of conceptus factors that inhibited PGF production, Day-14 conceptus membranes were placed inside bags constructed of dialysis tubing and co-incubated with endometria from Day-14 pregnant mares. PGF production was significantly reduced when membranes were in bags with molecular weight exclusion limits of 12,000, 6000, and 3500, but not of 1000, suggesting that conceptus PGF-inhibitory fact...
Hawkins DL, MacKay RJ, Gum GG, Colahan PT, Meyer JC.In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyz...
Kouba JM, Burns TA, Webel SK.The effects of dietary marine-derived n-3 fatty acids (FA) on mare milk and mare and foal plasma FA, postpartum ovarian follicular growth and prostaglandin concentrations were evaluated. Sixty days prior to expected foaling dates, mares were assigned to one of three diets: corn oil (CORN, n = 6), docosahexaenoic acid (DHA) diet (D; 12.64 g/d, n = 7), or eicosapentaenoic acid (EPA) and DHA (ED; 8.84 g EPA, 10.43 g DHA/d, n = 7). Milk and plasma were collected for FA analysis. Follicular data were recorded through the first postpartum ovulation. Post-ovulation serial blood samp...
Ealy AD, Eroh ML, Sharp DC.The equine embryo must signal its presence to the uterus for pregnancy to continue to term. Mobility of the conceptus throughout the uterus is crucial for its survival, and this action presumably permits the conceptus to transmit its antiluteolytic signal to the endometrium. Studies were completed to establish whether this unidentified antiluteolytic signal targets prostaglandin G/H synthase 2 (PGHS2), a rate limiting enzyme in converting arachidonic acid to prostaglandins (PGs). In the first study, quantitative RT-PCR was used to determine the relative abundance of PGHS2 mRNA in endometrium d...
Neuenschwander HM, Moreira JJ, Vendruscolo CP, Fülber J, Seidel SRT, Michelacci YM, Baccarin RYA.The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treat...
Wilsher S, Allen WR.The maternal recognition of pregnancy (MRP) signal in the mare has not been determined, although oestrogens have been proposed as a potential candidate. Objective: To determine effects of intrauterine administration of oestrogen and various oils on cyclic luteolysis in the mare. Objective: Intrauterine oestradiol or fatty acids may suppress luteolysis in the cycling mare when administered during late dioestrus. Methods: A single 1 ml dose of slow-release oestradiol (10 mg/ml) in fractionated coconut oil was infused into the uterine lumen of cycling mares on Days 6, 8, 10, 12 or 14 post ovulati...
Klein C."Maternal recognition of pregnancy" (MRP) is commonly used to describe the ongoing embryo-maternal communication during early pregnancy that culminates in prevention of luteolysis and ensures ongoing progestin support. The conceptus-derived pregnancy recognition signal has not yet been identified in the mare. Although equine conceptuses produce substantial amounts of estrogens, there is a lack of evidence that estrogens are the pregnancy recognition signal in mares. Conceptus mobility is integral to MRP and is driven by conceptus-derived prostaglandin production. Cessation of conceptus mobilit...
Lees P, Landoni MF.Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) ...
MacNicol JL, Lindinger MI, Pearson W.Exercise is a physiological stress resulting in reactive oxygen species and inflammatory mediators, the accumulation of which are thought to contribute to degenerative articular diseases. The horse is of particular interest in this regard as equine athletes are frequently exposed to repetitive bouts of high-intensity exercise. The purpose of this study was to provide a detailed description of the response of articular and systemic oxidative and inflammatory biomarkers following high-intensity, exhaustive exercise in horses. A group of horses (Ex) underwent repeated bouts of high-intensity exer...
Baccarin RY, Rasera L, Machado TS, Michelacci YM.Osteoarthritis (OA) of the metacarpophalangeal joint is the most common articular disease in polo ponies leading to early retirement. A biomarker that would discriminate between pathological and physiological changes secondary to exercise could be helpful in OA prevention. The aim of this study was to investigate the effects of polo training on synovial fluid biomarkers of inflammation and cartilage turnover in polo ponies of different skill levels. Synovial fluid samples were collected from metacarpophalangeal joints of polo ponies before and during the polo season (320 d). Nucleated cells, s...
Frisbie DD, Kawcak CE, Baxter GM, Trotter GW, Powers BE, Lassen ED, McIlwraith CW.To determine effects of intra-articularly administered 6alpha-methylprednisolone acetate (MPA) in exercised horses with carpal osteochondral fragmentation. Methods: 18 horses: 3 groups of 6 each. Methods: An osteochondral (chip) fragment was created in 1 randomly chosen middle carpal joint of each horse. Polyionic fluid (PF) was injected into both middle carpal joints of horses in the control group. In horses of the MPA-control group, MPA was injected into the middle carpal joint without an osteochondral fragment; a similar volume of PF was injected into the contralateral middle carpal joint. ...
Silva ES, Scoggin KE, Canisso IF, Troedsson MH, Squires EL, Ball BA.The objective of this study was to compare expression of estrogen receptor alpha (ER-α), β (ER-β), progesterone receptor (PR), as well as prostaglandin E2 type 2 (EP2) and 4 (EP4) receptors in the equine myometrium and endometrium during estrus, diestrus and early pregnancy. Tissues were collected during estrus, diestrus, and early pregnancy. Transcripts for ER-α (ESR1), ER-β (ESR2), PR (PGR), EP2 (PTGER2) and EP4 (PTGER4) were quantified by qPCR. Immunohistochemistry was used to localize ER-α, ER-β, PR, EP2 and EP4. Differences in transcript in endometrium and myometrium were compared ...
King JN, Gerring EL.Post operative ileus (POI) is a common and serious complication of colic surgery in the horse. There is a high correlation between the incidence of POI and the presence of ischaemic bowel, suggesting a role for endotoxin. 0.1 micrograms/kg endotoxin was administered intravenously to six ponies with chronically implanted gastrointestinal electromechanical recording devices. It produced profound disruption of normal fasting bowel motility patterns, with an inhibition of gastric contraction amplitude and rate, left dorsal colon contraction product and small colon spike rate. In the small intestin...
