Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

Abstract

In late pregnant cows, progesterone (P-4) is mainly of luteal origin. However, the trophoblast may provide high local P-4 concentrations in the uterus. To test for the importance of a complete P-4 withdrawal for parturition-related processes and placental release, the P-4 receptor (PGR) blocker aglepristone (Ap) was administered to three cows on days 270 and 271 of pregnancy. A complete opening of the cervix was observed 46.5 +/- 7.3 h after the start of treatment. However, expulsion of the calves was impaired obviously because of insufficient myometrial activity, and placental membranes were retained for at least 10 days. Measurement of P-4 concentrations indicated that PGR blockage induced luteolysis. To investigate the role of P-4 withdrawal for the prepartal tissue remodeling of the placentomes, the caruncular epithelium was evaluated by morphometry, and the percentage of trophoblast giant cells (TGCs) relative to the total number of trophoblast cells were assessed. Caruncular epithelium in Ap-treated cows (D272 + Ap) was immature (30.5 +/- 3.3%) and not different from untreated controls (elected cesarean section (CS) on day 272; D272-CS; 31.5 +/- 1.4%), whereas it was significantly reduced at normal term (D280.5 +/- 1.3; 21.0 +/- 6.1%; P=0.011). Correspondingly, the percentage of TGCs were 20.1 +/- 1.4 in D272 + Ap, 22.1 +/- 4.8 in D272-CS, and 9.8 +/- 3.9 at term (P=0.001). No effect was detected on placental estrogen synthesis. The results showed that in late pregnant cows, P-4 withdrawal only induces a limited spectrum of the processes related to normal parturition and is not a crucial factor for the prepartal tissue remodeling in placentomes and the timely release of the placenta.