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.
Ginther OJ.Prolonged luteal activity is one of the most formidable terminology challenges in mare reproductive biology. Prolonged luteal activity can be a result of persistence of an individual corpus luteum or the sequential development of luteal glands, each of which may have a normal life span. Luteal tissue can originate from an unovulated follicle or from an ovulation occurring during either follicular or luteal dominance. These complexities, together with ambiguous and inconsistent terminology, have resulted in confusion regarding those conditions which can be grouped broadly under the term prolong...
Watson ED, Sertich PL.Corpora lutea (CL) were collected from mares during early (Day 4-5), mid- (Day 8-9), and late (Day 12-13) dioestrus. Dispersed cell suspensions were obtained by enzymic digestion of tissue. Two distinct luteal cell populations (large and small) were observed. The proportion of small luteal cells significantly increased as age of CL advanced. Cells (2 x 10(6)) from CL which were incubated for 24 h secreted prostaglandin (PG) F, PGE-2 and 6-keto-PGF-1 alpha (the stable metabolite of prostacyclin). Higher concentrations of all PGs were produced by cells from CL at early dioestrus than from those ...
Wilde MH, Dinger JE, Hoagland TA, Graves-Hoagland RL, Woody CO.Transcervical diagnostic techniques may alter the length of the equine estrous cycle and affect subsequent luteal function. Therefore, nine mares were used to determine the effect of cervical dilation on plasma 13, 14-dihydro, 15-keto-prostaglandin F(2) (PGFM), progesterone (P(4)) and posttreatment duration of luteal function. Mares were given a daily score of 0 to 4 based on sexual receptivity. Five days following the end of receptivity, mares were randomly assigned to one of three, 3 x 3 latin squares. Control mares received no cervical dilation. Cervically stimulated mares recieved cervical...
Gilbert RO.Luteolysis with subsequent shortening of diestrus has been reported to follow equine endometrial biopsy performed early in the luteal phase of the estrous cycle, but a comprehensive study of the effect of endometrial biopsy on cycle length at different times of the cycle has not been reported. In this study, endometrial biopsies were obtained from four different pony mares on each of Days 0, 4, 8, 12, 16 and 20 after ovulation as determined by serial palpation per rectum. Compared with control cycles in the same mares, the ovulatory interval was shortened in mares from which biopsies were obta...
Pascoe DR, Stabenfeldt GH, Hughes JP, Kindahl H.Thirty mares with normal estrous cycles were allotted equally to 5 groups and infused with 250 ml of saline (NaCl) solution in utero on the seventh day after ovulation to test the effects of temperature, osmolarity, or pH of the saline solution on prostaglandin F2 alpha (PGF2 alpha) release and luteolysis. Intrauterine infusion of phosphate-buffered saline solution failed to alter the duration of the luteal phase, compared with the control group. Similarly, increasing the temperature of phosphate-buffered saline solution to 42 C or increasing (600 mosm) or decreasing osmolarity (less than 10 m...
Pascoe DR, Stover SM.A surgical technique for removal of one conceptus from mares with twin concepti more than 35 days of gestational age was evaluated. One conceptus was removed surgically from each of 15 mares carrying twin concepti that were 41 to 65 days of gestational age. As determined by ultrasonography, eight mares had bicornuate and seven mares had unicornuate twin concepti. For maintenance of pregnancy if surgical trauma should cause prostaglandin release and luteolysis, progesterone was administered prophylactically. Flunixin meglumine was administered perioperatively to minimize prostaglandin release. ...
McDowell KJ, Sharp DC, Grubaugh W, Thatcher WW, Wilcox CJ.Cycling pony mares were bred and used to test the effect of restricted conceptus mobility on luteal maintenance (i.e. maternal recognition of pregnancy). In Experiment 1, uterine horns were ligated to restrict conceptus mobility to one uterine horn, Group 1; one horn plus the uterine body, Group 2; or one horn, the body and approximately 80% of the second horn, Group 3. Pregnancies were monitored with real-time ultrasonography. Four of five mares in Group 1 and two of four mares in Group 2 returned to estrus (Day 16.0 +/- 1.9 and 14.5 +/- 0.7, respectively) and subsequently lost the embryonic ...
King SS, Evans JW.Follicular growth, circulating estradiol concentrations and endometrial prostaglandin F2 alpha (PGF2 alpha) production were measured to determine whether there is an interrelationship among these factors associated with luteolysis. Follicular growth was monitored by rectal palpation every other day during diestrus in 16 mares. Plasma estradiol was determined for daily samples during all estrous cycles. Endometrial tissue was removed for PGF2 alpha analysis by radioimmunoassay on d 10, 12, 14 or 16 during several normal cycles and after d 30 during spontaneously prolonged cycles. Circulating es...
Kastelic JP, Adams GP, Ginther OJ.Luteal progesterone was removed by an injection of prostaglandin F2alpha or bilateral ovariectomy on Day 12 of pregnancy in pony mares. The embryonic vesicle remained mobile in the uterus until loss occurred on Days 13, 13, 15, or 19 in four prostaglandin-treated mares and Days 15, 17, 19, or 26 in four ovariectomized mares. Exogenous progesterone given daily, starting on Day 12, maintained pregnancy until Day 40 in five of five prostaglandin-treated and three of four ovariectomized mares. During two-hour mobility trials on Day 14, embryonic vesicles in mares without luteal or exogenous proges...
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...
Adams GP, Kastelic JP, Bergfelt DR, Ginther OJ.The incidence of intrauterine fluid collections during dioestrus (12/43, 28%) and uterine cysts throughout the oestrous cycle (11/73, 15%) found in this study indicates that these ultrasonically detectable abnormalities are prevalent in mares. The hypothesis that uterine cysts do not affect pregnancy was not supported. Intrauterine fluid collections at dioestrus represented the presence of an inflammatory process as indicated by a high biopsy score, reduced progesterone concentrations, and a shorter interovulatory interval. Mares with fluid collections at dioestrus had a lower pregnancy rate a...
Jeffcott LB, Hyland JH, MacLean AA, Dyke T, Robertson-Smith G.Pregnant Standardbred mares were allocated to 2 groups. On Day 45 of gestation, 20-45 ml saline (240 g NaCl/l) were injected into the fetal sacs of 10 mares, and the other 10 mares were given sham treatment. Post-operative plasma oestrone sulphate concentrations were lower (P less than 0.01) on Days 48-55 in saline-treated mares than in sham-treated mares. Mean plasma progesterone profiles were similar in the two groups of mares, although post-operative luteolysis occurred in 4 saline-treated mares. There was no difference in plasma CG profiles between the 2 groups, except that CG concentratio...
Sirois J, Betteridge KJ, Goff AK.The outcome of 23 collections and reinsertions of conceptuses on Days 10.5-13.5, 4 transfers of Day-10.5, and 13 transfers of Day-6.5 embryos (ovulation = Day 0) was monitored in 30 mares. Blood samples were taken before and after each procedure to measure plasma 15-keto-13,14-dihydroprostaglandin F-2 alpha (PGFM), and then daily for progesterone determinations. Mares were also subjected to daily teasing for detection of oestrus, and to uterine ultrasonography for tracing the development of the conceptus. After the reinsertions, 12/23 conceptuses were detectable immediately after the procedure...
Tetzke TA, Ismail S, Mikuckis G, Evans JW.From a group of 11 cyclic mares, blood samples were collected at 3-min intervals for 2 h and at 15-min intervals for an additional 6 h during four stages of the oestrous cycle. Mean plasma oxytocin concentrations (pg/ml, LSM +/- se) were greater on Day 15 after ovulation (169.9 +/- 17.6) than on Day 0 (82.6 +/- 17.6; P less than 0.01), Day 3 (97.2 +/- 20.4, P less than 0.01) and Day 7 after ovulation (104.0 +/- 25.0, P less than 0.05). Oxytocin was secreted in a pulsatile manner throughout the oestrous cycle, with short (0-29 min), medium (30-89 min) and long (greater than 90 min) duration rhy...
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...
Driancourt MA, Palmer E.An experiment was carried out on pony mares to establish the time of the oestrous cycle at which ovarian follicles are recruited for ovulation. In one group (n=7), the cycle was interrupted at the preovulatory stage by removing the preovulatory follicle; in another group (n=13) the cycle was interrupted at day 6 of the luteal phase by inducing luteolysis with a prostaglandin injection (PG). In a subgroup (n=7) of those given PG, the ovary not bearing the corpus luteum was removed at the time of injection. A further group (n=6) served as surgical controls. The interval to the next ovulation and...
Zarrilli A, Lacalandra GM, Minoia P.In mare, sheep and bitch the action of PGF2 alpha have been studied in the early pregnancy. Prostin F2 alpha (Upjohn) and Gabbrostim (Vetem ) are commercial names of PGF2 alpha used at doses which are luteolytic in the non pregnant female. Seric progesterone showed a temporaneous decrease but after four or five days the initial values were restored and none of the experimental females aborted. In the opinion of authors, embryo per se and/or with its adnexa might have interacted blocking the mechanism of luteolysis induced by the administration of PGF2 alpha.
Mattioli M, Galeati G, Seren E.Prostaglandin F-2 alpha (PGF-2 alpha) receptors of bovine and equine corpora lutea (C.L.) were studied. From both the equilibrium binding data and the dissociation kinetics behaviour, two affinity classes of receptors are evident in the mare, with apparent dissociation constants (Kd) of 1,5 x 10(-9) M and 3.5 x 10(-8) M. Bovine PGF-2 alpha receptors present a homogeneous population of binding sites with Kd = 1 x 10(-8) M. Both bovine and equine C.L. receptors bind PGF-2 alpha in a specific manner; only 13, 14-dihydro-PGF-2 alpha considerably cross-reacts with these receptors. Since in the mare...
Howey WP, Jochle W, Barnes WJ.Alfaprostal (K 11941), a novel prostaglandin F2 alpha analogue was clinically tested in 24 dioestrous mares, 40 anoestrous mares and 31 postpartum mares, all being given 2 or 3 mg intramuscularly. Blood samples were taken for the determination of plasma progesterone levels and the objective confirmation of luteolytic drug effects. Two hundred and thirty-six mares at the same location were used for comparisons of the rates of pregnancy, early embryonic loss and foaling. Alfaprostol was found to act as a potent luteolytic agent with good oestrus induction, follicular development and normal conce...
Baker CB, Newton DI, Mather EC, Oxender WD.The length of diestrus was not changed in 4 mares by taking endometrial biopsy specimens during estrus. In contrast, taking endometrial biopsy specimens on postovulation day 4 induced premature luteolysis and significantly (P less than 0.05) reduced the length of diestrus. A concurrent decrease in serum progesterone occurred to verify the premature luteolysis in these mares. Bacterial cultures of endometrial swab samples from these mares were negative for growth at the first estrus before and after the last biopsy procedures, indicating that luteolysis was induced by the biopsy procedure and w...
Taverne MA, van der Weyden GC, Fontijne P, Dieleman SJ, Pashen RL, Allen WR.Uterine electromyography was performed by means of chronically implanted surface electrodes in 3 Pony mares during spontaneous oestrous cycles and following luteolysis induced by a prostaglandin analogue (fluprostenol). Three distinct patterns were recognized during the oestrous cycle. (1) During oestrus well defined phases of activity with closely grouped high-amplitude spikes were separated by long periods (10-45 min) of complete inactivity. (2) During dioestrus more diffuse phases of activity with low-amplitude spikes were separated by variable periods of relative inactivity. (3) During lut...
Neely DP, Stabenfeldt GH, Kindahl H, Hughes JP, Kendrick JW.The intrauterine infusion of 500 ml of warm sterile saline solution into mares on days 12, 13, or 14 after ovulation failed to alter the ovulatory interval, although intervals were shorter for days 12 and 13 (20.6 days) when compared with those in control mares (21.6 days). The IU fusion shortened luteal-life-span on days 12 (12.0 vs 13.8 days) and 13 (13.0 vs 14.4 days) (P is less than 0.05), but not day 14 (14.0 vs 13.5 days), when comparing the effects of IU infusion with an average of before and after base-line data. There was no effect on the interval from corpus luteum regression to ovul...
Neely DP, Stabenfeldt GH, Sauter CL.Daily injections of 150 units oxytocin administered to 6 mares on Days 4, 5, 6, 7 and 8 after ovulation (Day 0 = ovulation) failed to induced luteolysis as indicated by the maintenance of normal plasma progestagen concentrations and the occurrence of normal ovulatory intervals. Three additional mares were given oestrogen injections 24 h before an injection of oxytocin on Day 7 after ovulation, but this treatment also failed to induce luteolysis since plasma progestagen concentrations were maintained in all three mares. Two mares exhibited normal ovulatory intervals, while the third developed a...
Cuervo-Arango J, Newcombe JR.The objective of this study was to establish and characterize the relationship between the dose of cloprostenol (37.5, 250, 500 and 750 μg) and the age of the early corpus luteum (CL) (80, 88, 96, 104 and 112 h) on the luteolytic response of mares. Behavioural oestrus and ultrasonographic signs of return to oestrus were considered as the occurrence of full luteolysis. A total of 298 mares were divided into groups according to dose of cloprostenol and CL age. There was an effect of dose of cloprostenol (p < 0.001) and age of the CL at the time of treatment (p 0.05); and that of 500 similar...
Segabinazzi LGTM, Landers M, Kent A, Peterson E, Gilbert R, French H.Due to the limited literature available evaluating doses of Prostaglandin F2α in donkeys, doses for horses have been extrapolated and used as guidelines. This study aimed to assess the efficacy and side effects of four different cloprostenol sodium and dinoprost tromethamine doses to induce luteolysis in jennies. Sixty-three cycles of seven Jennies (nine cycles per jenny) were used in this study. Seven days after ovulation, jennies randomly received one of the treatments in a crossover design as follows: Control, no treatment was administered; C1, 250 µg of cloprostenol sodium (CS, Estrumate...
Ginther OJ, Beg MA.The temporal relationships between a pulse of 13,14-dihydro-15-keto-PGF(2alpha) (PGFM) and the concentrations of circulating hormones during the luteolytic period were studied for 11 pulses in 11 mares (Equus caballus) using samples collected hourly. Mean PGFM pulses encompassed 4h before to 4h after the peak, and hormone data were normalized to the PGFM peak (Hour 0). Concentration of progesterone decreased (P < 0.05) between Hours -4 and -3 and continued to decrease linearly throughout the PGFM pulse. The concentrations of cortisol and prolactin increased (P < 0.004) during Hours -4 to...
Hannan MA, Haneda S, Murata K, Takeuchi S, Cheong SH, Nambo Y.Until now, there have been no reports of foals born through embryo transfer after artificial insemination using frozen semen in Japan. The aims of this study were to develop a riding crossbred horse and evaluate the prospects of embryo transfer technology in multiplying horse population. In both donor and recipient mares, luteolysis was induced by the administration of 0.1 mg Cloprostenol to synchronize the onset of estrus, and ovulation was induced by administering 2000 IU human chorionic gonadotropin (hCG) or 0.75 mg Deslorelin. Frozen semen from an Irish Connemara pony stallion was used to ...
Silvia PJ, Meyer SL, Fitzgerald BP.Twelve horse mares were used in a repeated-measures design consisting of 3 replicates of 4 mares each. On Day 6 following ovulation, luteolysis was initiated with an i.m. injection of prostaglandin F2 alpha (PGF2 alpha; Lutalyse, 10 mg). Either 12 (-12) or 36 (-36) h before PGF2 alpha (PRE), blood samples were collected simultaneously from the intercavernous sinus (ICS) and jugular (JUG) vein at 10-min intervals for an 8-h period. Pituitary capacity to exogenous GnRH (2 micrograms/kg BW, i.v.) was evaluated at the alternate time point within this period. Frequent sampling and GnRH challenge we...
Ginther OJ.The estrous cycles of heifers and mares are used for illustrating pitfalls at the animal level in research in reproductive biology. Infrequent monitoring for characterizing the change in hormone concentrations or for detecting a reproductive event can be a pitfall when the interval for obtaining data exceeds the interval between events. For example, hourly collection of blood samples has shown that the luteolytic period (decreasing progesterone) encompasses 24 hours in heifers and mares. Collection of samples every 6-24 hours results in the illusion that luteolysis requires 2-3 days, owing to ...
Lawler DF, Brazil TJ, Dagleish MP, Watson ED.This study investigated the chemotactic activity of equine CL at different stages of the oestrous cycle. The purpose of this was to ascertain whether luteal tissue itself contributes to the massive influx of leucocytes around the time of natural and induced luteal regression. Corpora lutea were collected at different stages of dioestrus and after treatment with PGF2alpha. Culture medium harvested after incubation of luteal tissue for 20 h was chemotactic for both polymorphonuclear and mononuclear cells in late dioestrus (before functional regression) as well as after natural and induced luteal...
Watson ED, Bae SE, Al-Zi'abi MO, Hogg CO, Armstrong DG.The insulin-like growth factors, IGF-I and -II, have been shown to play a key role in luteal function in some species. The IGF binding proteins, IGFBP-2 and -3, have been shown to inhibit binding of IGF-I and -II to bovine luteal cells and decrease progesterone production. We have recently shown that equine follicles have the genetic capacity to produce IGFBP-2, and that levels decrease in healthy preovulatory follicles. In the present study expression of mRNAs encoding IGFBP-2, as well as the rate-limiting steroidogenic enzyme, P450scc, were studied in equine corpora lutea to investigate whet...
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...
Kenney RM, Ganjam VK, Cooper WL, Lauderdale JW.Seventy-three Standardbred and Thoroughbred mares in clinical anoestrus during the breeding season were treated with PGF2alpha. The mares were divided into four categories; foaling, barren, maiden and unknown. The response was consistent in all groups. Mares at Days 2 to 4 of dioestrus showed no decrease in plasma progesterone levels, and those at Days 6 to 8 showed a return of progesterone to baseline levels (less than 1 ng/ml) in 24 to 48 hr after treatment. Plasma progesterone levels returned to basal levels in 24 to 48 hr in 93% of mares; progesterone levels had not changed by 96 hr in 7% ...
Woodley SL, Burns PJ, Douglas RH, Oxender WD.This study was designed to test if oestradiol treatment would prevent or delay luteolysis in mares. Mares (5/group) received 0, 0.1, 1.0 or 10.0 mg oestradiol-17 beta daily from the day of ovulation until the next ovulation or for a maximum of 32 days. This treatment did not prevent luteolysis which occurred 15.8, 16.8, 15.8 and 17.3 days after the previous ovulation for the mares treated with 0, 0.1, 1.0 and 10.0 mg oestradiol respectively. Although oestradiol treatment failed to alter oestrous behaviour after luteolysis, daily treatment with 10.0 mg oestradiol prevented follicular growth and...
Ginther OJ.Recent findings on the luteolytic process in mares are reviewed and differences from other farm species are noted. It is well known that the luteolysin, PGF2α (PGF), is secreted from the endometrium in the absence of pregnancy in farm animal species. But PGF is a potent chemical and safeguards have evolved so that only the corpus luteum (CL) is affected. The safeguards include a short PGF half-life and secretion in two or three pulses per day. In mares, endogenous PGF travels from the uterus to the CL through the systemic circulation, but the luteal-cell membranes are highly efficient in capt...
Baker CB, Newton DI, Mather EC, Oxender WD.The length of diestrus was not changed in 4 mares by taking endometrial biopsy specimens during estrus. In contrast, taking endometrial biopsy specimens on postovulation day 4 induced premature luteolysis and significantly (P less than 0.05) reduced the length of diestrus. A concurrent decrease in serum progesterone occurred to verify the premature luteolysis in these mares. Bacterial cultures of endometrial swab samples from these mares were negative for growth at the first estrus before and after the last biopsy procedures, indicating that luteolysis was induced by the biopsy procedure and w...
Vernon MW, Strauss S, Simonelli M, Zavy MT, Sharp DC.The binding of prostaglandin (PG) F-2 alpha to corpora lutea (CL) from pregnant and non-pregnant Pony mares was examined. Studies of the rates of association and dissociation indicated that [3H]PGF was bound specifically and reversibly to a luteal cell membrane preparation (MP) that was isolated by high speed (100,000 g) ultracentrifugation. Various PGs and PG metabolites displaced [3H]PGF from the receptors in the following decreasing order: PGF-2 alpha greater than 13, 14-dihydro-PGF-2 alpha = 13,14-dihydro-15-keto PGF-2 alpha greater than PGD-2 greater than PGF-1 alpha = PGE-2 greater than ...
Zarrilli A, Lacalandra GM, Minoia P.In mare, sheep and bitch the action of PGF2 alpha have been studied in the early pregnancy. Prostin F2 alpha (Upjohn) and Gabbrostim (Vetem ) are commercial names of PGF2 alpha used at doses which are luteolytic in the non pregnant female. Seric progesterone showed a temporaneous decrease but after four or five days the initial values were restored and none of the experimental females aborted. In the opinion of authors, embryo per se and/or with its adnexa might have interacted blocking the mechanism of luteolysis induced by the administration of PGF2 alpha.
King SS, Evans JW.Follicular growth, circulating estradiol concentrations and endometrial prostaglandin F2 alpha (PGF2 alpha) production were measured to determine whether there is an interrelationship among these factors associated with luteolysis. Follicular growth was monitored by rectal palpation every other day during diestrus in 16 mares. Plasma estradiol was determined for daily samples during all estrous cycles. Endometrial tissue was removed for PGF2 alpha analysis by radioimmunoassay on d 10, 12, 14 or 16 during several normal cycles and after d 30 during spontaneously prolonged cycles. Circulating es...