Cyclooxygenase-2 differentially directs uterine angiogenesis during implantation in mice.
Increased vascular permeability and angiogenesis at the site of blastocyst apposition in the uterus are two hallmarks of the implantation process. The present investigation shows that although the proangiogenic vascular endothelial growth factor (VEGF) and its receptor, Flk-1, are primarily important for uterine vascular permeability and angiogenesis prior to and during the attachment phase of the implantation process, VEGF in complementation with the angiopoietins and their receptor, Tie-2, directs angiogenesis during decidualization following implantation. Mice with null mutation for the gene encoding cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin (PG) biosynthesis, show implantation and decidualization failure. Using reporter and mutant mice, we show here that COX-2-derived prostaglandins (PGs) are important for uterine vascular permeability and angiogenesis during implantation and decidualization, suggesting that one cause of the failure of these latter processes in Cox-2-/- mice is the deregulated vascular events in the absence of COX-2. The attenuation of uterine angiogenesis in these mice is primarily due to defective VEGF signaling and not due to the defective angiopoietin system.
Matsumoto
Hiromichi
H
Department of Molecular and Integrative Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160-7336, USA.
Ma
Wen-Ge
WG
Daikoku
Takiko
T
Zhao
Xhume
X
Paria
Bibhash C
BC
Das
Sanjoy K
SK
Trzaskos
James M
JM
Dey
Sudhansu K
SK
D000818:Animals; D001755:Blastocyst / Q000473:pathology; D051546:Cyclooxygenase 2; D010064:Embryo Implantation; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007763:Lac Operon; D008222:Lymphokines / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009154:Mutation; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor; D013997:Time Factors; D014599:Uterus / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007527:Isoenzymes; D008222:Lymphokines; D011453:Prostaglandins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor