Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation

Previous observations of ovulation and fertilization defects in cyclooxygen ase-2 (COX-2)-deficient mice suggested that COX-2-derived ovarian prostagla ndins (PGs) participate in these events. However, the specific PG and its m ode of action were unknown. Subsequent studies revealed that mice deficient in EP2, a PCE2-receptor subtype, have reduced litter size, apparently resu lting from poor ovulation but more dramatically from impaired fertilization . Using a superovulation regimen and in vitro culture system, we demonstrat e herein that the ovulatory process, not follicular growth, oocyte maturati on, or fertilization, is primarily affected in adult COX-2- or EP2-deficien t mice. Furthermore, our results show that in vitro-matured and -fertilized eggs are capable of subsequent preimplantation development. However, sever ely compromised ovulation in adult COX-2- or EP2-deficient mice is not mani fested in immature (3wk-old) COX-2- or EP2-deficient mice, suggesting that the process of ovulation is more dependent on PGs in adult mice. Although t he processes of implantation and decidualization are defective in COX-2(-/- ) mice, our present results demonstrate that these events are normal in EP2 -deficient mice, as determined by embryo transfer and experimentally induce d decidualization. Collectively, previous and present results suggest that whereas COX-2-derived PGE(2) is essential for ovulation via activation of E P2, COX-2-derived prostacyclin is involved in implantation and decidualizat ion via activation of peroxisome proliferator-activated receptor delta.