Endogenous and exogenous effects of PGF2α during luteolysis in mares.
Abstract: 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 the PGF2α and PGF2α+FM groups but not in the controls (n = 5). In a study of spontaneous luteolysis, the same FM dose was given every 6 h from Day 13 until Day 17 or earlier if CL regression was indicated by an 80% decrease in luteal blood-flow signals. Blood was sampled for progesterone assay each day and 8 h of hourly blood sampling was done each day to characterize PGFM concentrations and pulses. Progesterone (P4) was lower (P < 0.05) in controls than in an FM group (n = 7) by Day 15. Luteolysis (P4 < 1 ng/mL) ended on Days 14-19 in individual controls. In contrast, luteolysis did not end until after Day 20 in 4 of 7 FM-treated mares. In the three mares with completion of luteolysis before Day 20 in the FM group, the interval from beginning to end of luteolysis was longer (P < 0.02) (4.5 ± 0.6 days) than in the controls (3.0 ± 0.4 days). During 8-h sessions of hourly blood sampling on Day 14, concentration of PGFM was significantly lower in the FM group for the minimal, mean, and maximal per session. Pulses of PGFM were identified by a CV methodology on each day in 7 of 7 and 3 of 7 mares in the controls and FM group, respectively. The four FM-treated mares without a CV-identified pulse were the four mares in which luteolysis did not occur before Day 20. In mares with detected pulses, PGFM was lower at each nadir and at the peak (86% lower) in the FM group than in controls, but the interval between nadirs or base of a pulse was not different between groups. Hypothesis 1 that endogenous PGF plays a role in the luteolytic effect of exogenous PGF2α was not supported. Hypothesis 2 that an inhibitor of PGF2α biosynthesis prevented or minimized the prominence of PGFM pulses and increased the frequency of persistent CL was supported.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication Date: 2019-04-09 PubMed ID: 30991168DOI: 10.1016/j.theriogenology.2019.04.004Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Clinical Trial
- Veterinary
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research explores the impact of an inhibitor of Prostaglandin F2 alpha (PGF2α), flunixin meglumine (FM), on the luteolytic effect of exogenous PGF2α in mares. It concludes that this inhibitor does not appear to impact the luteolytic effect but does seem to minimize PGF2α pulses and extend the lifecycle of corpora lutea.
Research Objective and Methods
- The study aimed to understand the role of endogenous hormones, specifically PGF2α, during luteolysis—the degradation of the corpus luteum—in mares. Researchers attempted to determine whether an inhibitor of PGF2α synthesis (FM) might affect the luteolytic effect, and how this might reveal the role of endogenous PGF2α in this process.
- Pulses of PGF2α and its metabolite, PGFM, were tracked via an infusion system that mimicked the natural occurrence of such pulses. In addition, the study examined the impact of administering FM 1 hour before and 5 hours after these infusions.
Results and Outcomes
- The study showed that the decrease in progesterone was similar in both the PGF2α and the PGF2α+FM groups, indicating that FM did not affect the luteolytic action of PGF2α.
- In a sub-study of spontaneous luteolysis, when the same dose of FM was administered repeatedly, progesterone levels dropped less than in the control group, suggesting a slowing down of the luteolytic process.
- In the mares treated with FM, luteolysis tended to occur later than in untreated mares, and the interval from beginning to end of luteolysis was significantly longer.
- During hourly blood sampling on Day 14, the concentration of PGFM was significantly lower in the FM group, suggesting that the drug may affect PGF2α production or release.
- Pulses of PGFM were lowered in the FM-treated mares compared to the control group, supporting the idea that FM can minimize PGFM pulses while also increasing the frequency of a persisting corpus luteum.
Conclusions
- The study did not support the idea that endogenous PGF plays a role in the luteolytic effect of exogenous PGF2α. This means that inhibiting PGF2α did not affect the degradation of the corpus luteum.
- The experiment supported the hypothesis that an inhibitor of PGF2α biosynthesis could minimize the prominence of PGFM pulses and lead to a longer-lived corpus luteum. This result suggests that PGF2α inhibitor may be a potential therapeutic agent for mares who have difficulty maintaining pregnancy due to premature luteolysis.
Cite This Article
APA
Ginther OJ, Domingues RR, Kennedy VC, Dangudubiyyam SV.
(2019).
Endogenous and exogenous effects of PGF2α during luteolysis in mares.
Theriogenology, 132, 45-52.
https://doi.org/10.1016/j.theriogenology.2019.04.004 Publication
Researcher Affiliations
- Eutheria Foundation, Cross Plains, WI, 53528, USA; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA. Electronic address: oj.ginther@wisc.edu.
- Eutheria Foundation, Cross Plains, WI, 53528, USA; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA.
- Eutheria Foundation, Cross Plains, WI, 53528, USA.
- Eutheria Foundation, Cross Plains, WI, 53528, USA.
MeSH Terms
- Abortifacient Agents, Nonsteroidal / administration & dosage
- Abortifacient Agents, Nonsteroidal / metabolism
- Abortifacient Agents, Nonsteroidal / pharmacology
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Clonixin / administration & dosage
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Corpus Luteum / metabolism
- Dinoprost / administration & dosage
- Dinoprost / metabolism
- Dinoprost / pharmacology
- Female
- Horses
- Luteolysis / drug effects
- Ovulation / drug effects
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
