Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation.

Matsumoto H, Ma W, Smalley W, Trzaskos J, Breyer RM, Dey SK
Biol Reprod. 2001 64 (5): 1557-65

PMID: 11319164 · 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 delta.

MeSH Terms (24)

Animals Blastocyst Chorionic Gonadotropin Cyclooxygenase 2 Decidua Embryo Implantation Embryo Transfer Female Fertilization in Vitro Humans Isoenzymes Membrane Proteins Mice Mice, Knockout Oocytes Ovary Ovulation Prostaglandin-Endoperoxide Synthases Prostaglandins Receptors, Cytoplasmic and Nuclear Receptors, Prostaglandin E Receptors, Prostaglandin E, EP2 Subtype Superovulation Transcription Factors

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