Diversification of Cyclooxygenase-2-Derived Prostaglandins in Ovulation and Implantation

• Published in: Biology of reproduction Vol. 64; no. 5; pp. 1557 - 1565
• Main Authors: MATSUMOTO, Hiromichi, MA, Wen-Ge, SMALLEY, Whitney, TRZASKOS, James, BREYER, Richard M, DEY, Sudhansu K
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01.05.2001
• Subjects: Animals; Biological and medical sciences; Blastocyst - physiology; Chorionic Gonadotropin - pharmacology; Cyclooxygenase 2; Decidua - physiology; Embryo Implantation; Embryo Transfer; Female; Fertilization in Vitro; Fundamental and applied biological sciences. Psychology; Humans; Isoenzymes - deficiency; Isoenzymes - genetics; Isoenzymes - physiology; Membrane Proteins; Mice; Mice, Knockout; Mother. Fetoplacental unit. Mammary gland. Milk; Oocytes - physiology; Ovary - drug effects; Ovulation; Pregnancy. Parturition. Lactation; Prostaglandin-Endoperoxide Synthases - deficiency; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - physiology; Prostaglandins - physiology; Receptors, Cytoplasmic and Nuclear - physiology; Receptors, Prostaglandin E - deficiency; Receptors, Prostaglandin E - genetics; Receptors, Prostaglandin E - physiology; Receptors, Prostaglandin E, EP2 Subtype; Superovulation; Transcription Factors - physiology; Vertebrates: reproduction; Prostaglandin-endoperoxide synthase; Enzyme; Arachidonic acid derivatives; Rodentia; Fecundation; Ovulation; Decidualization; Pregnancy; Vertebrata; Mammalia; Ovum implantation; Mouse; Eicosanoid; Oxidoreductases
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod64.5.1557

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 δ.