IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY


37.5g of d-cloprostenolc induced complete luteolysis, similar to that in mares receiving 250 g of a d,l- cloprostenol preparation.12 The recommended la- beled doses for d-cloprostenol and d,l-cloprostenol are 37.5 g per mare (0.5-mL injection volume) and 250g (1-mL injection volume), respectively, admin- istered subcutaneously or intramuscularly.


4. Luteolytic Effects of PGF and Stage of the Estrous Cycle


The results presented in the early studies in the 1970s provided the basis for the assumption that PGF formulations would not induce luteolysis or affect CL function if administered before day 5 or 6 after ovulation. Interestingly, some of these stud- ies reported that some mares actually responded to PGF-induced luteolysis when treated on day 3 after ovulation3; however, the notion that the early CL was not responsive to PGF administration remained ingrained in the scientific and veterinary profes- sional community. In 1974, Thompson and With- erspoon13 briefly reported another phenomenon that has recently gained attention: the ability of PGF to induce partial luteolysis followed by resurgence in CL function characterized by a transient increase in concentrations of blood progesterone. In that study, two mares receiving a relatively low dose of a synthetic PGF analogue 9 days after ovulation be- gan to have a decrease in concentrations of plasma progesterone at 12 hours after PGF treatment, fol- lowed by a resurgence in progesterone concentra- tions at 48 hours after treatment; progesterone concentrations then remained at 30% to 50% of that before PGF treatment. More recently, 32 years from that initial report, Bergfelt et al14 (2006) com- pared the pattern of luteolysis after PGF treatment as a single bolus injection on day 3 after ovulation with that of mares treated on day 10. In the day 3 group, 75% (12/16) of mares had CL resurgence. Among those, six mares with “minor” progesterone resurgence had treatment-to-ovulation intervals similar to that in control mares. In summary, CL resurgence after PGF treatment results in partial luteolysis of the CL. Partial luteolysis is evident by decreasing concentrations of blood progesterone and followed by CL function resurgence. The resur- gence is denoted by a moderate increase in proges- terone concentrations. Partial luteolysis followed by CL resurgence may occur after administration of sub-luteolytic boluses doses of PGF during mid di- estrus,13,15,16 or after administration of single injec- tions at day 3 after ovulation.14


5. Effects of Exogenous PGF on Steroid and Gonadotropin Secretion


Administration of PGF in mares with a functional CL 5 days is followed by functional luteolysis (sig- nificant decrease in progesterone) 24 hours after treatment that is, however, preceded by an immedi- ate, transient rise in progesterone shortly after PGF treatment. Noden et al17 reported that functional


luteolysis was preceded by a transient increase in progesterone, estradiol, and leuteinizing hormone at 10, 30, and 60 minutes after PGF treatment of di- estrual mares. In a more recent study by Ginther et al,18 administration of a single luteolytic intrave- nous bolus of PGF resulted in an immediate increase in circulating progesterone concentrations within 10 minutes after the bolus injection, accompanied by an increase in concentrations of follicle-stimulating hormone, leuteinizing hormone, and cortisol. Con- versely, mares infused with PGF for 2 hours, mim- icking a natural pulse of endogenous PGF action, did not show increases in the same hormones; however, both treatments, bolus injection and infusion, re- sulted in similar luteolytic effects. These effects on steroids and gonadotropin secretion associated with supraphysiologic doses of PGF may partially explain the results of one study that found that mares treated in estrus with a synthetic PGF, fenpros- talene, had shorter estrus-to-ovulation intervals than did control mares.19


6. PGF Treatment and Antiluteogenesis


Recently, it has been reported that luteolysis or pre- vention of luteal formation may be accomplished with PGF administration beginning as early as the day ovulation is detected. This effect is dependent on the dose and frequency of PGF treatments. On the basis that the early developing CL5 days is actually responsive to luteolytic effects of PGF, a series of experiments conducted in our laboratory produced data that support the hypothesis that the early developing CL is indeed responsive to exoge- nous PGF as early as within the first 24 hours from ovulation.20,21 Because of this early luteolytic re- sponsiveness to PGF administration before the CL is fully functional, we named this phenomenon as (PGF-induced) “antiluteogenesis.” Mares treated once or twice daily for 3 days with 2.5 or 10 mg of PGF dinoprost failed to show a significant rise in concentrations of plasma progesterone during the treatment period. Approximately 60% of mares treated twice daily for 3 days with 10 mg of PGF had complete luteolysis; all mares receiving once- daily 2.5 mg of PGF for 3 days showed CL resur- gence. Therefore, the antiluteogenesis effect of PGF is dependent on the dose and frequency of PGF treatments.


7. Clinical Applications of PGF in Broodmare Management


Use of PGF to Induce Luteolysis and Return to Estrus


Termination of the luteal phase (“short-cycling”) with exogenous PGF may be attempted for planned breeding of a single mare or as an approach to syn- chronize estrus and ovulation in a group of mares. If reproductive examinations with palpation per rectum and transrectal ultrasonography are avail- able, the predictability of onset of estrus and ovula-


AAEP PROCEEDINGS  Vol. 59  2013 339


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