Multiple female reproductive failures in cyclooxygenase 2-deficient mice.
Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In spite of long-standing speculation, definitive roles of PGs in various events of early pregnancy remain elusive. We demonstrate herein that the targeted disruption of COX-2, but not COX-1, in mice produces multiple failures in female reproductive processes that include ovulation, fertilization, implantation, and decidualization. Using multiple approaches, we conclude that these defects are the direct result of target organ-specific COX-2 deficiency but are not the result of deficiency of pituitary gonadotropins or ovarian steroid hormones, or reduced responsiveness of the target organs to their respective hormones.
Lim
H
H
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Paria
B C
BC
Das
S K
SK
Dinchuk
J E
JE
Langenbach
R
R
Trzaskos
J M
JM
Dey
S K
SK
D000818:Animals; D001755:Blastocyst / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003656:Decidua / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D005306:Fertilization / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects / Q000235:genetics*; D010544:Peroxidases / Q000172:deficiency / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics*; D011555:Pseudopregnancy; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000235:genetics; D013256:Steroids / Q000502:physiology; D014599:Uterus / Q000502:physiology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D013256:Steroids; D002772:Cholera Toxin; D011464:Epoprostenol; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse