An early single dose of progesterone agonist attenuates endogenous progesterone surge and reduces ovulation rate in immature rat model of induced ovulation

Abstract

Inhibition of preovulatory synthesis and action of progesterone impairs ovulation in rodents. We evaluated effects of supplementation of exogenous progesterone on human chorionic gonadotropin (hCG)-induced ovulatory response in immature rats. Equine CG-primed mature follicles responded to hCG with induction of immunoreactive steroidogenic acute regulatory protein (StAR) mainly in thecal layers and a transient enhancement in progesterone synthesis peaking at 6h after hCG (hCG6h). A single dose of natural progesterone or a synthetic agonist (MP) at hCG0h both decreased ovulation rates in dose-dependent manners. MP was still effective when treated at hCG4h. Treatment with these agents at hCG0h reduced circulating progesterone and thecal expression of StAR at hCG6h. The treatments further attenuated induction of cyclooxygenase (COX)-2 in mural granulosa cells and ovarian prostaglandin (PG) E(2) level at hCG8h. We also found a significant reduction in bromo-deoxyuridine incorporation by mural granulosa cells. Obtained results show that the early treatment with exogenous progesterone agonist caused attenuated amplitude of endogenous progesterone surge, reduced COX-2/PGE(2) system, dysregulated mitosis of granulosa cells, and decreased oocytes release. We suggest that optimal progesterone synthesis and action are an early critical component of hCG-initiated ovulatory cascade that regulates biochemical function of granulosa cells.