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Lim, H, Gupta, RA, Ma, WG, Paria, BC, Moller, DE, Morrow, JD, DuBois, RN, Trzaskos, JM and Dey, SK (1999) Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev. 13:1561-74
We have demonstrated previously that cyclo-oxygenase-2 (COX2), the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs), is essential for blastocyst implantation and decidualization. However, the candidate PG(s) that participates in these processes and the mechanism of its action remain undefined. Using COX2-deficient mice and multiple approaches, we demonstrate herein that COX2-derived prostacyclin (PGI2) is the primary PG that is essential for implantation and decidualization. Several lines of evidence suggest that the effects of PGI2 are mediated by its activation of the nuclear hormone receptor PPARdelta, demonstrating the first reported biologic function of this receptor signaling pathway.
Animals; Cell Nucleus/metabolism; Cyclooxygenase 2; Cytochrome P-450 Enzyme System/genetics; Cytochrome P-450 Enzyme System/metabolism; Decidua; Dimerization; Embryo Implantation/physiology; Endometrium; Epoprostenol/genetics; Epoprostenol/metabolism; Female; Gene Expression; Genes, Reporter; Intramolecular Oxidoreductases/genetics; Intramolecular Oxidoreductases/metabolism; Isoenzymes/genetics; Isoenzymes/metabolism; Luciferases/genetics; Mice; Mice, Knockout; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Prostaglandin-Endoperoxide Synthases/genetics; Prostaglandin-Endoperoxide Synthases/metabolism; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Epoprostenol; Receptors, Prostaglandin/metabolism; Receptors, Retinoic Acid/genetics; Retinoid X Receptors; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic