79 A single intrauterine infusion of flunixin meglumine on gestational day 29 results in pregnancy loss in beef cows

Late embryonic mortality (LEM) is a major concern in the beef cattle industry, yet the underlying physiological mechanisms by which this occurs are still largely unknown. Cows undergoing LEM have decreased circulating concentrations of prostaglandin F2a metabolite (PGFM) and increased concentrations of prostaglandin E2 metabolite (PGEM) from gestational days (GD) 30–38, corresponding to the period of active pregnancy termination. The overall objective of this study was to analyze the physiological effects of inhibiting local prostaglandin (PG) synthesis during late embryonic development in beef cows. We hypothesized that infusion of flunixin meglumine (FM), a COX 1 and 2 inhibitor, on GD 29 would alter the local PG secretion and negatively affect placentation and ultimately terminate pregnancy. All cows were submitted to a 7-day COsync + CIDR protocol (GD −10) and induced to ovulate and artificially inseminated on GD 0 (n = 18). On GD 27, pregnant cows were fitted with coccygeal vein polyethylene catheters. Pregnancy was confirmed by the presence of a fetal heartbeat on GD 27 via ultrasonography, and subsequent blood collections began every 8 h via venipuncture (n = 7) or every 4 h via tail cannula (n = 2). Cows were randomly assigned to receive an intrauterine infusion of either 240 mg of FM diluted in 10 mL of flush medium (ABT; FMTrt; n = 6), or 10 mL of flush medium (CON; n = 3) every 8 h beginning on GD 29. Both infusion solutions were corrected to a pH of 7.2. Plasma concentrations of PGEM and PGFM were quantified using a validated commercial ELISA (Cayman Chemical). To measure the rate at which FM entered circulation following intrauterine infusion, serum was sent to a commercial laboratory for analysis of peripheral FM (TVMDL). Data were analyzed in SAS (version 9.4) using PROC MIXED. All pregnant cows in the FMTrt group had their pregnancies terminated after a single infusion of FM; however, all CON cows maintained their pregnancies. Failed pregnancies were confirmed via ultrasound by the absence of a viable fetal heartbeat 8 h after the initial infusion. Peripheral FM was detectable as early as 2 h after intrauterine infusion. In FMTrt cows, there was a significant decline in PGFM and a tendency for PGEM to be reduced after one infusion of FM (50.48 vs. 14.86 pg mL⁻¹; P = 0.0004 and 8.50 vs. 3.74 pg mL⁻¹; P = 0.06, respectively). However, upon pregnancy failure induced by a single FM infusion, concentrations of PGEM in the FMTrt group increased compared with CON cows (7.27 vs. 1.37 pg mL⁻¹; P < 0.0001). The increase in PGEM observed following FM infusion accords with previous data and may indicate a compensatory mechanism to rescue the dying embryo. In conclusion, intrauterine FM infusion perturbs the secretion of PGs from the uterus and results in pregnancy failure. These data suggest that PGs are critically important for this period of pregnancy and placental development. Further research is required to fully understand the physiological contributions of PGs to pregnancy and placentation in cattle.