Group IVA phospholipase A₂ optimizes ovulation and fertilization in rodents through induction of and metabolic coupling with prostaglandin endoperoxide synthase 2

Female mice lacking group IVA phospholipase A₂ (Pla2g4a ^-/-) have a smaller litter size, which is due, in part, to defective implantation. We examined PLA₂G4A dependence of the processes of ovulation and fertilization. Following induction of ovulation by equine chorionic gonadotropin (eCG)/human CG (hCG) treatment and mating, ovulation and fertilization rates were reduced significantly in Pla2g4a^-/- mice as compared to wild-type littermates. Human CG triggered robust ovarian prostaglandin (PG) E₂ production in the preovulatory period that was significantly attenuated in Pla2g4a^-/- mice. Human CG transiently enhanced ovarian expression of PLA₂G4A and prostaglandin endoperoxide synthase 2 (PTGS2) in wild-type mice. This PTGS2 induction was decreased in Pla2g4a^-/- mice and also in immature rats treated with the PLA ₂G4A inhibitor, archidonyl trifluoromethyl ketone. A close spatiotemporal association of PLA₂G4A with PTGS2 was found in mouse and rat preovulatory follicles examined by immunohistochemistry. Less association was observed with 4 other forms of PLA₂. Our data strongly suggest that PLA₂G4A amplifies hCG induction of PTGS2 and colocalizes with the induced PTGS2, thus contributing to robust PG production required for optimal ovulation and fertilization in rodents.