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1 May 2001 Diversification of Cyclooxygenase-2-Derived Prostaglandins in Ovulation and Implantation
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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 EP2, a PGE2-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 EP2-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 EP2-deficient mice is not manifested in immature (3-wk-old) COX-2- or EP2-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 EP2-deficient mice, as determined by embryo transfer and experimentally induced decidualization. Collectively, previous and present results suggest that whereas COX-2-derived PGE2 is essential for ovulation via activation of EP2, COX-2-derived prostacyclin is involved in implantation and decidualization via activation of peroxisome proliferator-activated receptor δ.

Hiromichi Matsumoto, Wen-ge Ma, Whitney Smalley, James Trzaskos, Richard M. Breyer, and Sudhansu K. Dey "Diversification of Cyclooxygenase-2-Derived Prostaglandins in Ovulation and Implantation," Biology of Reproduction 64(5), 1557-1565, (1 May 2001).
Received: 24 October 2000; Accepted: 1 January 2001; Published: 1 May 2001

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