Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation.
Previous observations of ovulation and fertilization defects in cyclooxygenase-2 (COX-2)-deficient mice suggested that COX-2-derived ovarian prostaglandins (PGs) participate in these events. However, the specific PG and its mode of action were unknown. Subsequent studies revealed that mice deficient in EP(2), a PGE(2)-receptor subtype, have reduced litter size, apparently resulting from poor ovulation but more dramatically from impaired fertilization. Using a superovulation regimen and in vitro culture system, we demonstrate herein that the ovulatory process, not follicular growth, oocyte maturation, or fertilization, is primarily affected in adult COX-2- or EP(2)-deficient mice. Furthermore, our results show that in vitro-matured and -fertilized eggs are capable of subsequent preimplantation development. However, severely compromised ovulation in adult COX-2- or EP(2)-deficient mice is not manifested in immature (3-wk-old) COX-2- or EP(2)-deficient mice, suggesting that the process of ovulation is more dependent on PGs in adult mice. Although the processes of implantation and decidualization are defective in COX-2(-/-) mice, our present results demonstrate that these events are normal in EP(2)-deficient mice, as determined by embryo transfer and experimentally induced decidualization. Collectively, previous and present results suggest that whereas COX-2-derived PGE(2) is essential for ovulation via activation of EP(2), COX-2-derived prostacyclin is involved in implantation and decidualization via activation of peroxisome proliferator-activated receptor delta.
Matsumoto
H
H
Department of Molecular and Integrative Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160-7338, USA.
Ma
W
W
Smalley
W
W
Trzaskos
J
J
Breyer
R M
RM
Dey
S K
SK
D000818:Animals; D001755:Blastocyst / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D003656:Decidua / Q000502:physiology; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000502:physiology; D010053:Ovary / Q000187:drug effects; D010060:Ovulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013480:Superovulation; D014157:Transcription Factors / Q000502:physiology
D006063:Chorionic Gonadotropin; D007527:Isoenzymes; D008565:Membrane Proteins; C545644:PTGER2 protein, human; D011453:Prostaglandins; C545645:Ptger2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases