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PMID:10385625

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Citation

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

Abstract

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.

Links

PubMed PMC316805

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PTGIS

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PTGIS

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PTGIS

acts_upstream_of_or_within

GO:0007566: embryo implantation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PTGIS

acts_upstream_of_or_within

GO:0046697: decidualization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RXRA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P35396

F

Seeded From UniProt

complete

MOUSE:RXRA

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PPARD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P28700

F

Seeded From UniProt

complete

MOUSE:PPARD

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PPARD

acts_upstream_of_or_within

GO:0007566: embryo implantation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PPARD

enables

GO:0046982: protein heterodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P28700

F

Seeded From UniProt

complete

MOUSE:PPARD

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PGH2

acts_upstream_of_or_within

GO:0046697: decidualization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857239

P

Seeded From UniProt

complete

MOUSE:PGH2

acts_upstream_of_or_within

GO:0007566: embryo implantation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857239

P

Seeded From UniProt

complete

Notes

See also

References

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