Endogenous and exogenous effects of PGF2α during luteolysis in mares

An inhibitor of PGF2 alpha biosynthesis (flunixin meglumine, FM) was used to study the role of endogenous PGF2 alpha on the luteolytic effect of exogenous PGF2 alpha in mares. A 2-h infusion of PGF2 alpha 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 PGF2 alpha metabolite (PGFM). Treatment with FM (1.7 mg/kg) was done 1 h before and 5 h after the start of PGF2 alpha infusion. In hourly blood samples beginning 1 h before the start of PGF2 alpha infusion, progesterone decreased (P < 0.05) similarly by 5 h in each of the PGF2 alpha and PGF2 alpha+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 PGF2 alpha was not supported. Hypothesis 2 that an inhibitor of PGF2 alpha biosynthesis prevented or minimized the prominence of PGFM pulses and increased the frequency of persistent CL was supported. (C) 2019 Elsevier Inc. All rights reserved.