Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta.
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.
Lim
H
H
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7338, USA.
Gupta
R A
RA
Ma
W G
WG
Paria
B C
BC
Moller
D E
DE
Morrow
J D
JD
DuBois
R N
RN
Trzaskos
J M
JM
Dey
S K
SK
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003656:Decidua; D019281:Dimerization; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium; D011464:Epoprostenol / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D007527:Isoenzymes; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D008156:Luciferases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase