Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Blastocyst / physiology
-
Cholera Toxin / pharmacology
-
Cyclooxygenase 1
-
Cyclooxygenase 2
-
Decidua / drug effects
-
Dose-Response Relationship, Drug
-
Embryo Implantation / drug effects
-
Embryo Implantation / genetics*
-
Enzyme Inhibitors / pharmacology
-
Epoprostenol / pharmacology
-
Female
-
Fertilization / drug effects
-
Fertilization / genetics*
-
Gene Expression Regulation / physiology
-
Isoenzymes / deficiency
-
Isoenzymes / genetics*
-
Membrane Proteins
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout / physiology*
-
Ovulation / drug effects
-
Ovulation / genetics*
-
Peroxidases / deficiency
-
Peroxidases / genetics
-
Platelet Aggregation Inhibitors / pharmacology
-
Pregnancy
-
Prostaglandin-Endoperoxide Synthases / deficiency
-
Prostaglandin-Endoperoxide Synthases / genetics*
-
Pseudopregnancy
-
RNA, Messenger / analysis
-
Receptors, Prostaglandin E / genetics
-
Steroids / physiology
-
Uterus / physiology
Substances
-
Enzyme Inhibitors
-
Isoenzymes
-
Membrane Proteins
-
Platelet Aggregation Inhibitors
-
RNA, Messenger
-
Receptors, Prostaglandin E
-
Steroids
-
Cholera Toxin
-
Epoprostenol
-
Peroxidases
-
Cyclooxygenase 1
-
Cyclooxygenase 2
-
Prostaglandin-Endoperoxide Synthases
-
Ptgs1 protein, mouse