Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARδ

  1. Hyunjung Lim,
  2. Rajnish A. Gupta,
  3. Wen-ge Ma,
  4. Bibhash C. Paria,
  5. David E. Moller,
  6. Jason D. Morrow,
  7. Raymond N. DuBois,
  8. James M. Trzaskos, and
  9. Sudhansu K. Dey
  1. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7338 USA; Department of Gastroenterology/Medicine, Vanderbilt University, Nashville, Tennessee 37232-2279 USA; Merck Research Laboratories, Rahway, New Jersey 07065 USA; Department of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6602 USA; The DuPont Pharmaceuticals Company, Wilmington, Delaware 19880 USA

Abstract

We have demonstrated previously that cyclo-oxygenase-2 (COX2), the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs), is essential for blastocyst implantation and decidualization. However, the candidate PG(s) that participates in these processes and the mechanism of its action remain undefined. Using COX2-deficient mice and multiple approaches, we demonstrate herein that COX2-derived prostacyclin (PGI2) is the primary PG that is essential for implantation and decidualization. Several lines of evidence suggest that the effects of PGI2 are mediated by its activation of the nuclear hormone receptor PPARδ, demonstrating the first reported biologic function of this receptor signaling pathway.

Keywords

Footnotes

  • Corresponding author.

  • E-MAIL sdey{at}kumc.edu; FAX (913) 588-5677.

    • Received March 23, 1999.
    • Accepted April 27, 1999.
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