Luteolysis in horses refers to the physiological process by which the corpus luteum, a temporary endocrine structure in the ovaries, undergoes regression. This process results in the cessation of progesterone production, a hormone necessary for maintaining pregnancy. In mares, luteolysis is typically initiated by the release of prostaglandin F2α from the uterine lining, which signals the corpus luteum to degenerate. The timing and regulation of luteolysis are integral to the equine estrous cycle, influencing the mare's reproductive status and fertility. This page compiles peer-reviewed research studies and scholarly articles that examine the mechanisms, hormonal regulation, and implications of luteolysis in equine reproductive health.
Beyer T, Rink BE, Scarlet D, Walter I, Kunert S, Aurich C.In the horse, it is still unclear if and to what extent low progestin concentration contributes to early conceptus loss. In the present study, we have investigated if reduced or elevated progestin concentration in the early luteal phase influences endometrial function and conceptus development. We hypothesized that reduced progestin concentration via delayed downregulation of endometrial progesterone receptors (PR) influences endometrial function in healthy fertile mares while progestin substitution does not. Genitally healthy estrous mares (n = 8; age 4-14 years) were inseminated and trea...
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...
Galvão A, Wolodko K, Rebordão MR, Skarzynski D, Ferreira-Dias G.In the present report we describe the involvement of transforming growth factor B1 (TGF) in functional regression and structural luteolysis in the mare. Firstly, TGF and its receptors activin-like kinase (ALK) 5 and TGF receptor 2 were identified in corpus luteum (CL) steroidogenic, endothelial and fibroblast-like cells. Also, TGF and ALK5 protein expression were shown to be increased in Mid-, and Late-CL (p < 0.05). Subsequently, using an in vitro model with Mid-CL cells, we studied the role of TGF on secretory activity and cell viability. Cell treatment with TGF decreased progesterone...
Betteridge KJ, Raeside JI, Waelchli RO, Christie HL, Hayes MA.Sixteen cases of spontaneous pregnancy loss (11 of singletons and five of pairs of twins) are described. The losses occurred between gestation Days 13 and 25 in 12 mares being monitored almost daily by transrectal ultrasonography (for measurement of conceptus growth) and blood sampling (for determination of maternal plasma progesterone concentrations as evidence of luteolysis) in experimental studies of early pregnancy. In 10 of the 16 cases the uterus was flushed and eight conceptuses were recovered for morphological assessment. Five of the 11 losses of singletons occurred before Day 16 and, ...
Oliveira Neto IV, Canisso IF, Segabinazzi LG, Dell'Aqua CPF, Alvarenga MA, Papa FO, Dell'Aqua JA.This study compared hormone treatments given to mares during anestrus, spring transition, and different stages of the estrous cycle, by assessing uterine features and pregnancy rates after embryo transfer (ET). Embryo recipient mares (n = 160) were equally arranged as follows: G1-spontaneous ovulation (control), G2-anestrus, G3-spring transition, G4-early estrus, G5-estrus, G6-diestrus, G7-early diestrus treated with a dose of dinoprost, and G8-early diestrus treated with two doses of dinoprost. At treatment initiation (Day-4), G2-7 were given dinoprost and estradiol-17β, thereafter, estr...
Ferreira JC, Filho LFN, Boakari YL, Canesin HS, Thompson DL, Lima FS, Meira C.The aim of the current project was to characterize the luteal vascularity and the plasma concentrations of progesterone (P4), prolactin (PRL) and 13,14-dihydro-15-keto-PGF (PGFM) in mares with luteal disturbances during early and mid-diestrus. In Experiment 1, twenty-one mares were treated with 2 mL of 0.9% NaCl, or 1 mg Dinoprost, or 10 mg Dinoprost on day two after ovulation (Control-D2, 1/10PGF-D2 and PGF-D2 groups, respectively; n = 7 mares/group). In Experiment 2, similar treatments were performed eight days post-ovulation using a different cohort of 21 mares (Control-D8, 1/10PGF-D8 ...
Garcia-Muñoz A, Valldecabres-Torres X, Newcombe JR, Cuervo-Arango J, Garcia-Rosello E.The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately...
Rebordão MR, Galvão A, Pinto-Bravo P, Pinheiro J, Gamboa S, Silva E, Mateus L, Ferreira-Dias G.Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin Fα, E and I synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Con...
Köhne M, Ille N, Erber R, Adib Razavi MS, Walter I, Aurich C.Progestin concentration in plasma during the early luteal phase is crucial for endometrial function and conceptus development. We hypothesized that periovulatory gonadotrophin treatment via support of luteal function affects endometrial gene expression in horses. Effect of age was analyzed as well. Shetland mares (n = 8, age 4-25 years) were assigned to the following treatments during five consecutive cycles in alternating order following a cross-over design: treatment hCG/-: preovulatory injection of hCG, but no gonadotrophin injection at detection of ovulation, treatment -/hCG: no preovulat...
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...
Kuhl J, Nagel C, Ille N, Aurich JE, Aurich C.In the present study we have evaluated a possible stress reaction in response to two different PGF2α analogs-luprostiol and D-cloprostenol--and their effects on estrous cycle characteristics. In a cross-over-design eight mares received in alternating order either luprostiol (Treatment LUP; 3.75 mg im), D-cloprostenol (Treatment CLO; 22.5μg im) or saline (Treatment CON; NaCl 0.9% 0.5ml im) on day 8 after ovulation. Injection of either LUP or CLO, but not of CON resulted in a significant decline of progesterone concentration in plasma to baseline concentrations within two days (time: p<0.00...
Kozai K, Tokuyama S, Szóstek AZ, Toishi Y, Tsunoda N, Taya K, Sakatani M, Takahashi M, Nambo Y, Skarzynski DJ, Yamamoto Y, Kimura K, Okuda K.In mares, prostaglandin F2α (PGF2α) secreted from the endometrium is a major luteolysin. Some domestic animals have an auto-amplification system in which PGF2α can stimulate its own production. Here, we investigated whether this is also the case in mares. In an in vivo study, mares at the mid-luteal phase (days 6-8 of estrous cycle) were injected i.m. with cloprostenol (250 µg) and blood samples were collected at fixed intervals until 72 h after treatment. Progesterone (P4) concentrations started decreasing 45 min after the injection and continued to decrease up to 24 h (P < 0.05). In t...
Diel de Amorim M, Nielsen K, Cruz RK, Card C.Intrauterine plant oil infusion, including fractionated coconut oil, has been previously found to be a safe, inexpensive, and reversible method of prolonging the luteal phase in mares when administered on Day 10 of the estrous cycle. Our objective was to understand the uteroovarian response to the administration of fractionated coconut oil infusion in the uterus of diestrous mares. We hypothesized that intrauterine coconut oil administration on Day 10 would prolong luteal life span in a dose-dependent fashion and would result in higher serum progesterone levels than untreated mares at the expe...
Ginther OJ, Baldrighi JM, Castro T, Wolf CA, Santos VG.In experiment 1, daily blood samples were available from Days 0 to 20 (Day 0 = ovulation) in mares with an interovulatory interval (IOI, n = 5) and in mares that developed idiopathic persistent corpus luteum (PCL, n = 5). The PCL was confirmed by maintenance of progesterone (P4) concentration until end of the experiment (Day 20). Significant interactions of group and day revealed the novel findings that luteinizing hormone (LH) was lower (P < 0.05) in the PCL group than that in the IOI group on Days 0 to 4, and prolactin was lower (P < 0.05) on Days 1, 4, 6, and 7. In experiment 2, treat...
Galvão A, Skarzynski D, Ferreira-Dias G.In the present work, we investigated the role of Nodal, an embryonic morphogen from the TGFβ superfamily in corpus luteum (CL) secretory activity using cells isolated from equine CL as a model. Expression pattern of Nodal and its receptors activin receptor A type IIB (ACVR2B), activin receptor-like kinase (Alk)-7, and Alk4, as well as the Nodal physiological role, demonstrate the involvement of this pathway in functional luteolysis. Nodal and its receptors were immune localized in small and large luteal cells and endothelial cells, except ACVR2B, which was not detected in the endothelium. Nod...
Ginther OJ, Castro T, Baldrighi JM, Wolf CA, Santos VG.Five mares that developed idiopathic persistent corpus luteum (PCL) were compared with 5 mares with apparently normal interovulatory intervals (IOIs). Progesterone (P4) and a metabolite of prostaglandin F2α (PGFM) were assayed daily beginning on the day of ovulation (Day 0). Transition between the end of an initial progressive P4 increase and the beginning of a gradual decrease in P4 occurred on mean Day 6. The gradual decrease in P4 between Days 6 and 12 was less (approached significance, P < 0.06) in the PCL group than in the IOI group. The P4 concentration on Day 12 (before luteolysis i...
Santos VG, Bettencourt EM, Ginther OJ.Persistent CL (PCL; n = 10) in mares was studied daily from Day 20 (Day 0 = ovulation) to the ending ovulation. In addition, the 10 days before ovulation at the end of a PCL were compared with the end of an interovulatory interval (IOI; n = 28) during the same months. Concentration of P4, cross-sectional area of CL, and percentage of CL with Doppler signals of blood flow during PCLs remained constant from 64 to about 33 days before the end of luteolysis and then decreased linearly. Concentration of LH between Day 20 and beginning of the ovulatory LH surge increased linearly. A dominant follicl...
Ginther OJ, Wolf CA, Baldrighi JM, Greene JM.Hourly circulating concentrations of a PGF2α metabolite (PGFM), progesterone (P4), and LH were obtained from a reported project, and concentrations of nitric oxide (NO) metabolites (NOMs; nitrates and nitrites) were determined in eight mares. Unlike the reported project, hormone concentrations were normalized to the peak of the first PGFM pulse of luteolysis (early luteolysis), second PGFM pulse (late luteolysis), and a pulse after luteolysis. The duration of luteolysis was 23.1 ± 1.0 hours, and the peak of the first and second PGFM pulses occurred 6.5 ± 0.9 and 14.8 ± 0.8 hours after the ...
Cuervo-Arango J, Mateu-Sánchez S, Aguilar JJ, Nielsen JM, Etcharren V, Vettorazzi ML, Newcombe JR.The objective of this study was to determine the effect of the interval from induced luteolysis to ovulation on fertility of mares from two different farms. At farm 1, 215 mares were inseminated with frozen/thawed semen during 513 estrous cycles over seven consecutive breeding seasons. Estrus was induced with analogues of PGF2α in 179 cycles. At farm 2, 375 embryo flushings were performed in 65 donor mares inseminated with fresh semen; of which, 327 were performed following artificial insemination after PGF-induced luteolysis. In both farms, the intervals from PGF treatment to ovulation (ITO)...
Santos VG, Castro T, Bettencourt EM, Ginther OJ.A procedure for oxytocin (OT) administration on Day 13 postovulation was developed in mares for stimulation of a pulse of PGFM (a PGF2α metabolite) that mimics a natural PGFM pulse during luteolysis. Bolus treatment with each of five OT doses (1-10 IU/mare, n = 3) stimulated a burst of PGFM that was maximum in 4 minutes and was unlike a natural pulse. A 2-hour OT infusion of 1.25, 2.5, or 5 IU/100 kg (n = 4) induced a PGFM pulse similar to reported pulses; lower doses did not. The peak of an induced pulse (approximately 260-380 pg/mL) seemed similar to reported natural peaks (approxima...
Santos VG, Bettencourt EM, Ginther OJ.Mares with persistent CL (PCL) with no known etiology (idiopathic) were matched with mares with an interovulatory interval (IOI) of apparent physiological length, so that ovulation at the beginning of each PCL and IOI occurred during the same month (n = 6/group). Blood samples were collected daily from Days 12 to 22 (Day 0 = ovulation). Mean progesterone (P4) decreased in both groups on Days 14 and 15 and then diverged with a continued decrease in the IOI group and the beginning of constant and greater (P < 0.05) P4 concentration on each day in the PCL group. Before P4 divergence betw...
Coffman EA, Pinto CR, Snyder HK, Leisinger CA, Cole K, Whisnant CS.A single dose of PGF2α does not consistently induce luteolysis in the equine CL until at least 5 days after ovulation, leading to the erroneous assumption that the early CL is refractory to the luteolytic effects of PGF2α. We hypothesized that serial administration of PGF2α in early diestrus would induce a return to estrus similar to mares treated with a single injection in mid-diestrus, and fertility of the induced estrus would not differ. The objectives of the study were to evaluate the effects of the 2 approaches as reflected by: (1) concentrations of plasma progesterone; (2) interovulat...
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...
Flores-Flores G, Velázquez-Cantón E, Boeta M, Zarco L.The effects of repeated cloprostenol administration were compared in mares impregnated by horses and mares impregnated by donkeys in order to assess the role of eCG on the development of pregnancy-associated resistance to the luteolytic and abortifacient effects of PGF2α. Eleven mares impregnated by donkey (mule pregnancy) and 9 mares impregnated by horse (horse pregnancy) were used. Six mares with mule pregnancy and four with horse pregnancy were injected with cloprostenol (0.25 mg) when they were between day 65 and day 75 of pregnancy, and the treatment was repeated 48, 72 and 96 h latter...
Kozai K, Hojo T, Tokuyama S, Szóstek AZ, Takahashi M, Sakatani M, Nambo Y, Skarzynski DJ, Okuda K.Regression of the corpus luteum (CL) is characterized by a decay in progesterone (P4) production (functional luteolysis) and disappearance of luteal tissues (structural luteolysis). In mares, structural luteolysis is thought to be caused by apoptosis of luteal cells, but functional luteolysis is poorly understood. 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes P4 into its biologically inactive form, 20α-hydroxyprogesterone (20α-OHP). In mares, aldo-keto reductase (AKR) 1C23, which is a member of the AKR superfamily, has 20α-HSD activity. To clarify whether AKR1C23 is associated wi...
Thorson JF, Prezotto LD, Cardoso RC, Allen CC, Alves BR, Amstalden M, Williams GL.Onset of the winter anovulatory period in mares is associated with a marked diminution in adenohypophyseal synthesis and release of LH. Native GnRH, unlike its synthetic agonists, stimulates the synthesis and secretion of LH in mares without pituitary refractoriness. Herein we tested the hypotheses that (1) the average Julian day of pregnancy can be accelerated by up to 2 months in winter anovulatory mares treated continuously with native GnRH beginning on February 1 and (2) mares will sustain luteal function and pregnancy after treatment withdrawal. Forty-two winter anovulatory mares were str...
Toishi Y, Tsunoda N, Tagami M, Hashimoto H, Kato F, Suzuki T, Nagaoka K, Watanabe G, Tokuyama S, Okuda K, Taya K.Evaluation of a new chemiluminescent enzyme immunoassay, the PATHFAST assay system (PATHFAST), for measurement of circulating progesterone in mares was performed. Five mares at the mid-luteal stage were administrated a single i.m. injection of prostaglandin F2α analog (PGF2α; cloprostenol 250 μg/ml), and then blood samples were collected from the jugular vein at 0, 15, 30 and 45 min, at one-hour intervals until 24 and at 48 hr via a catheter in the jugular vein. To monitor the physiological changes in circulating progesterone in mares after induced luteolysis, concentrations of progesterone...
Santos VG, Beg MA, Bettencourt EM, Ginther OJ.The effects of inhibition of PGF2α synthesis on luteolysis in mares and on the incidence of prolonged luteal activity were studied in controls and in a group treated with flunixin meglumine (FM), a PGF2α inhibitor (n = 6/group). The FM was given every 8 hours (1.0 mg/kg) on each of Days 14.0 to 16.7. Concentration (pg/mL) of PGF2α metabolite averaged over 8 hours of hourly blood sampling at the beginning of each day, was lower in the FM group than in the controls on Day 14 after ovulation (6.7 ± 1.3 vs. 13.8 ± 2.9, P < 0.05), Day 15 (15.0 ± 3.9 vs. 35.2 ± 10.4, P < 0.10), and Day 16 (21...
Al-Zi'abi MO, Fraser HM, Watson ED.In mares, little information is available on the type of cell death that occurs during natural and induced luteal regression. Corpora lutea were collected from mares in the early luteal phase, days 3-4 (n = 4); mid-luteal phase, day 10 (n = 5); early regression, day 14 (n = 4); late regression, day 17 (n = 4); and 12 and 36 h (n = 3 per group) after PGF2alpha administration on day 10. Histological and ultrastructural sections were examined and TUNEL was used to detect DNA fragmentation. In early luteal regression, there were more pyknotic luteal cells and extracellular round dense bodies compa...
Behrendt-Adam CY, Adams MH, Simpson KS, McDowell KJ.A positive-feedback loop between luteal oxytocin and uterine prostaglandin F2 alpha (PGF) is a major signal for luteolysis in ruminants. Likewise, uterine PGF causes luteolysis in mares, but the involvement of oxytocin in this process is unclear. We wanted: 1) to determine if the oxytocin-neurophysin I (OT-NP I) gene is transcribed into mRNA in the endometrium of mares; and, if so, 2) to analyze relative changes in abundance of endometrial OT-NP I mRNA throughout the estrous cycle and during early stages of pregnancy. Endometrial biopsies were obtained from nonbred mares during estrus, and 5, ...
Ginther OJ, Gastal MO, Gastal EL, Jacob JC, Beg MA.A follicular wave and luteolysis were induced in mares by ablation of follicles > or =6 mm and treatment with prostaglandin F(2alpha) (PGF) on Day 10 (where ovulation = Day 0). The incidence of haemorrhagic anovulatory follicles (HAFs) in the induced waves (20%) was greater (P < 0.007) than in preceding spontaneous waves (2%). Hormone and follicle dynamics were compared between induced follicular waves that ended in ovulations (ovulating group; n = 36) v. HAFs (HAF group; n = 9). The day of the first ovulation or the beginning of HAF formation at the end of an induced wave was designated as po...
Vanderwall DK, Silvia WJ, Fitzgerald BP.The reproductive tracts of nine thoroughbred mares were examined by ultrasound to determine the day of ovulation (day 0). Mares were fitted with intercavernous sinus cannulae on the day before the start of sample collection of pituitary venous effluent rich in oxytocin. Intercavernous sinus blood samples were collected for at least 36 h at 5 min intervals beginning at noon on day 13 (n = 2), day 15 (n = 5) or day 16 (n = 2) after ovulation. Concentrations of oxytocin and 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM) in plasma were determined by radioimmunoassay. Three high-magnitude surg...
Bergfelt DR, Woods JA, Ginther OJ.Characteristics of spontaneous embryonic loss in 21 mares were compared with those of 52 contemporary mares that maintained pregnancy. Embryonic losses were, in retrospect, grouped according to day of loss and length of the interovulatory interval, respectively, as follows: group 1, less than or equal to day 20 and less than or equal to 30 days (n = 10); group 2, less than or equal to day 20 and greater than 30 days (n = 3); and group 3, greater than day 20 and greater than 30 days (n = 8); ovulation was day 0. Mean diameter of the embryonic vesicle in group 1 was smaller (P less than 0.05) on...
Flores-Flores G, Velázquez-Cantón E, Boeta M, Zarco L.The effects of repeated cloprostenol administration were compared in mares impregnated by horses and mares impregnated by donkeys in order to assess the role of eCG on the development of pregnancy-associated resistance to the luteolytic and abortifacient effects of PGF2α. Eleven mares impregnated by donkey (mule pregnancy) and 9 mares impregnated by horse (horse pregnancy) were used. Six mares with mule pregnancy and four with horse pregnancy were injected with cloprostenol (0.25 mg) when they were between day 65 and day 75 of pregnancy, and the treatment was repeated 48, 72 and 96 h latter...
Kozai K, Tokuyama S, Szóstek AZ, Toishi Y, Tsunoda N, Taya K, Sakatani M, Takahashi M, Nambo Y, Skarzynski DJ, Yamamoto Y, Kimura K, Okuda K.In mares, prostaglandin F2α (PGF2α) secreted from the endometrium is a major luteolysin. Some domestic animals have an auto-amplification system in which PGF2α can stimulate its own production. Here, we investigated whether this is also the case in mares. In an in vivo study, mares at the mid-luteal phase (days 6-8 of estrous cycle) were injected i.m. with cloprostenol (250 µg) and blood samples were collected at fixed intervals until 72 h after treatment. Progesterone (P4) concentrations started decreasing 45 min after the injection and continued to decrease up to 24 h (P < 0.05). In t...
Diel de Amorim M, Bramer SA, Rajamanickam GD, Klein C, Card C.Our understanding of the temporal changes in endometrial and luteal gene transcripts related to the actions of oxytocin and prostaglandin during early equine pregnancy is incomplete. Additionally, the role of oxytocinase, also known as Leucyl-cystinyl aminopeptidase (LNPEP), during early pregnancy in mares has not been previously investigated. Luteal and endometrial biopsies were obtained on Day (D)8, D10, D12 and D15 post-ovulation in pregnant (PREG) and diestrus (DIEST) mares for real-time qPCR. Differences in endometrial gene expression occurred over time in: SLC2A4, SLC2A1, PTGES, OXTR and...
Bergfelt DR, Pierson RA, Ginther OJ.The present study was designed to characterize and compare the physiology and ultrasonographic morphology of the corpus luteum (CL) during regression and resurgence following a single dose of native prostaglandin F2alpha (PGF) given 3 days after ovulation, with a more conventional treatment given 10 days after ovulation. On the day of pre-treatment ovulation (Day 0), horse mares were randomly assigned to receive PGF (Lutalyse; 10 mg/mare, i.m.) on Day 3 (17 mares) or Day 10 (17 mares). Beginning on either Days 3 or 10, follicle and CL data and blood samples were collected daily until post-trea...
Ginther OJ.During an ovulatory follicular wave in the monovulatory species of heifers, mares, and women, the two largest follicles deviate in diameter at the end of a common follicle growth phase. The largest follicle before deviation becomes the future ovulatory follicle in most ovulatory waves. In 10-30% of the ovulatory waves, the destiny of the two follicles switches just before or at deviation so that the second-largest follicle becomes the future ovulatory follicle, and the largest follicle becomes a subordinate. In FSH-driven switching in heifers, mares, and women, the wave-stimulating FSH surge d...
Ginther OJ, Utt MD, Bergfelt DR, Beg MA.The interrelationships of progesterone, estradiol, and LH were studied in mares (n=9), beginning at the first ovulation (Day 0) of an interovulatory interval. An increase in mean progesterone concentrations began on Day 0 and reached maximum on Day 6, with luteolysis beginning on Day 14. A common progesterone threshold concentration of about 2 ng/ml for a negative effect on LH occurred at the beginning and end of the luteal phase. Progesterone and LH concentrations decreased at a similar rate from Day 6 until the onset of luteolysis on Day 14, consistent with a decreasing positive effect of LH...
Bae SE, Watson ED.It has been reported that oxytocin is produced not only in the hypothalamus and posterior pituitary but also in outside the classical hypothalamo-neurohypophyseal axis such as the ovary, testis, placenta and in some nonreproductive sites. In the mare, oxytocin-mRNA has been identified in the endometrium, and oxytocin and its neurophysin have been identified in the uterus. In the present study, oxytocin was localised in the endometrium of the mare at the light microscopic and ultrastructural level by immunostaining and immunogold labelling of endometrial biopsy specimens collected during estrus...
McCue PM, Farquhar VJ, Carnevale EM, Squires EL.Deslorelin implants, approved for use in inducing ovulation in mares, have been associated with prolonged interovulatory intervals in some mares. Administration of prostaglandins in the diestrous period, following a deslorelin-induced ovulation, has been reported to increase the incidence of delayed ovulations. The goals of the present study were: (1) to determine the percentage of mares given deslorelin that experience delayed ovulations with or without subsequent prostaglandin treatment, and (2) to determine if removal of the implant 48 h after administration would effect the interval to sub...
Daels PF, Starr M, Kindahl H, Fredriksson G, Hughes JP, Stabenfeldt GH.The infusion of Salmonella typhimurium endotoxin into pregnant mares resulted in a biphasic release pattern of PGF-2 alpha as determined by 15-keto-13,14-dihydro-PGF-2 alpha concentrations. The initial phase of 1 h duration was followed by accentuated release by 2 h after infusion; concentrations reached basal levels by 6 h. In 7 mares at 23, 26, 29, 33, 36, 53 and 55 days of gestation, fetal death occurred between 36 and 120 h after infusion; 12 mares at 46, 51, 56, 59, 65, 71, 73, 85, 103, 138, 283 and 318 days of gestation did not abort after endotoxin infusion. Luteal activity was compromi...
Ginther OJ, Gastal EL, Gastal MO, Beg MA.The effect of a single injection of prostaglandin F2alpha (PGF) during mid-diestrus on systemic concentrations of progesterone, LH, FSH, estradiol, and cortisol and on blood flow to the corpus luteum was studied in 10 controls and 10 PGF-treated mares. Blood flow was assessed by estimating the percentage of corpus luteum with color-Doppler signals of blood flow during real-time scanning of the entire structure and by the diameter of the vascular pedicle near its attachment to the ovary. Treatment was done 8 days after ovulation and 0 h was immediately before the treatment. Examinations and col...
Ginther OJ, Rodrigues BL, Ferreira JC, Araujo RR, Beg MA.Blood collections for characterising 13,14-dihydro-15-keto-PGF2alpha (PGFM) pulses in mares and colour-Doppler examinations for estimating percentage of corpus luteum with blood-flow signals were done hourly for a 24-h session on Day 15 (ovulation = Day 0; n = 13 mares) or during 12-h sessions from Days 12 to 16 (n= 10 mares). Luteolysis was defined as extending from the beginning of a precipitous decrease in progesterone until progesterone was <2 ng mL(-1). Comparisons were made among preluteolysis, luteolysis, and postluteolysis. Greater prostaglandin F2alpha activity (mean PGFM concentra...
Daels PF, DeMoraes JJ, Stabenfeldt GH, Hughes JP, Lasley BL.Thirty pregnant mares were assigned to 3 groups: Group 1 (n = 10) mares served as controls; Group 2 (n = 10) mares were treated with altrenogest (44 mg/day) from Day 16 to 80 and Group 3 (n = 10) mares were treated with a luteolytic dose of PGF2 alpha on Day 16 followed by altrenogest (44 mg/day) until Day 80. Concentrations of progesterone and chorionic gonadotrophin (CG) in plasma and oestrogen conjugate (OC) in urine were determined between Days 16 and 80 of gestation. In Group 3, complete luteolysis occurred in all 10 mares following administration of PGF2 alpha. Six of the 10 mares did no...
Cuervo-Arango J, Mateu-Sánchez S, Aguilar JJ, Nielsen JM, Etcharren V, Vettorazzi ML, Newcombe JR.The objective of this study was to determine the effect of the interval from induced luteolysis to ovulation on fertility of mares from two different farms. At farm 1, 215 mares were inseminated with frozen/thawed semen during 513 estrous cycles over seven consecutive breeding seasons. Estrus was induced with analogues of PGF2α in 179 cycles. At farm 2, 375 embryo flushings were performed in 65 donor mares inseminated with fresh semen; of which, 327 were performed following artificial insemination after PGF-induced luteolysis. In both farms, the intervals from PGF treatment to ovulation (ITO)...
Walewska E, Wołodko K, Skarzynski D, Ferreira-Dias G, Galvão A.The regulation of corpus luteus (CL) luteolysis is a complex process involving a myriad of factors. Previously, we have shown the involvement of Nodal in functional luteolysis in mares. Presently, we ask the extent of which Nodal mediation of luteolysis is done through regulation of angioregression. We demonstrated the interaction between Nodal and hypoxia-inducible factor 1 α (HIF1α) and thrombospondin 1/thrombospondin receptor (TSP1/CD36) systems, could mediate angioregression during luteolysis. First, we demonstrated the inhibitory effect of Nodal on the vascular marker platelet/endotheli...
Galvão A, Skarzynski D, Ferreira-Dias G.In the present work, we investigated the role of Nodal, an embryonic morphogen from the TGFβ superfamily in corpus luteum (CL) secretory activity using cells isolated from equine CL as a model. Expression pattern of Nodal and its receptors activin receptor A type IIB (ACVR2B), activin receptor-like kinase (Alk)-7, and Alk4, as well as the Nodal physiological role, demonstrate the involvement of this pathway in functional luteolysis. Nodal and its receptors were immune localized in small and large luteal cells and endothelial cells, except ACVR2B, which was not detected in the endothelium. Nod...
Castro T, Jacob JC, Stefani G, Domingues RR, Ginther OJ.The concentrations of progesterone (P4) and a metabolite of PGF2α (PGFM) in mares were compared between the interovulatory interval (IOI; n = 8) and the corresponding days of pregnancy (n = 9). In daily blood samples, P4 increased between the day of ovulation (Day 0) and ∼Day 6 and then gradually decreased until the beginning of luteolysis in the IOI group. Before the beginning of luteolysis, there were no significant differences in P4 concentrations between the IOI and early pregnancy. In the IOI, PGFM concentration on the day before the beginning of luteolysis began to increase (P <Â...
Nie GJ, Goodin AN, Braden TD, Wenzel JG.To determine whether administration of a microdose of prostaglandin at the BAI HUI acupuncture point offers any advantage over IM injections for luteolysis, ovulatory interval, or systemic response in mares. Methods: 17 mature cycling mares, 3 to 20 years of age and weighing 400 to 500 kg. Methods: Conventional and microdoses of the prostaglandin dinoprost tromethamine (PGF2alpha), the analogue cloprostenol, or sterile water (control) were administered to mares in 7 treatment groups. Treatments were assigned by dose, administration site (semimembranosus, semitendinosus, or lumbosacral region),...
Santos VG, Castro T, Bettencourt EM, Ginther OJ.A procedure for oxytocin (OT) administration on Day 13 postovulation was developed in mares for stimulation of a pulse of PGFM (a PGF2α metabolite) that mimics a natural PGFM pulse during luteolysis. Bolus treatment with each of five OT doses (1-10 IU/mare, n = 3) stimulated a burst of PGFM that was maximum in 4 minutes and was unlike a natural pulse. A 2-hour OT infusion of 1.25, 2.5, or 5 IU/100 kg (n = 4) induced a PGFM pulse similar to reported pulses; lower doses did not. The peak of an induced pulse (approximately 260-380 pg/mL) seemed similar to reported natural peaks (approxima...
Hershman L, Douglas RH.Two experiments were performed to deterine the critical time at which the equine blastocyst must be present within the uterus of the mare to prevent regression of the corpus luteum, and thus establish the critical time for the maternal recognition of pregnancy. A non-surgical blastocyst collection technique was developed to study this relationship between the blastocyst and the maternal ovary. Results from these experiments demonstrated that the cyclic life-span of the corpus luteum is not affected by the presence of the blastocyst within the mare's uterus until after Day 14 after ovulation. L...
Kozai K, Hojo T, Tokuyama S, Szóstek AZ, Takahashi M, Sakatani M, Nambo Y, Skarzynski DJ, Okuda K.Regression of the corpus luteum (CL) is characterized by a decay in progesterone (P4) production (functional luteolysis) and disappearance of luteal tissues (structural luteolysis). In mares, structural luteolysis is thought to be caused by apoptosis of luteal cells, but functional luteolysis is poorly understood. 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes P4 into its biologically inactive form, 20α-hydroxyprogesterone (20α-OHP). In mares, aldo-keto reductase (AKR) 1C23, which is a member of the AKR superfamily, has 20α-HSD activity. To clarify whether AKR1C23 is associated wi...
Gastal EL, Gastal MO, Nogueira GP, Bergfelt DR, Ginther OJ.The effect of altered LH concentrations on the deviation in growth rates between the 2 largest follicles was studied in pony mares. The progestational phase was shortened by administration of PGF2alpha on Day 10 (Day 0=ovulation; n=9) or lengthened by daily administration of 100 mg of progesterone on Days 10 to 30 (n=11; controls, n=10). All follicles > or = 5 mm were ablated on Day 10 in all groups to initiate a new follicular wave. The interovulatory interval was not altered by the PGF2alpha treatment despite a 4-day earlier decrease in progesterone concentrations. Time required for growt...
