Cyclooxygenase-2 derived PGE2 and PGI2 play an important role via EP2 and PPARdelta receptors in early steps of oil induced decidualization in mice

Placenta. 2008 Jun;29(6):523-30. doi: 10.1016/j.placenta.2008.03.001. Epub 2008 Apr 14.

Abstract

Differentiation of endometrial stromal cells into decidual cells (decidualization) is prerequisite for blastocyst implantation. Different prostanoids are shown to be involved in the cascade of events found in implantation and decidualization. Previous reports described that cyclooxygenase-2 (COX2) derived prostacyclin (PGI2) plays an important role via peroxisome proliferator activated receptor (PPARdelta) nuclear receptor in implantation and decidualization. Herein, we investigated the role of COX2 derived PGE2 and PGI2 and examined the protein expression and regulation of COX1, COX2, membrane-bound prostaglandin E synthase (mPGES-1), prostaglandin I synthase (PGIS), PGE2 receptor (EP2) and PPARdelta in hormone primed oil infused uterine horn as well as in non-infused uterine horn (control horn). Our results show that selective COX2 inhibitor (Nimesulide) inhibits decidualization while COX1 inhibitor (SC560) does not affect decidualization. COX2, mPGES-1, PGIS, EP2 and PPARdelta immunostaining are strongly observed at 24 h and 48 h in oil-induced horn and than significantly reduced at 72 h and 120 h and absent in non-infused horn. However COX1 immunostaining is observed in infused as well as in non-infused horn. Our immunohistochemical studies corroborated well with follow up western blotting of the same proteins. PGE2 and PGI2 products were also elevated at 24h and 48 h after oil induction in infused horn in comparison to control horn. Our data suggest that COX2 derived both PGE2 and PGI2 mediate its function via EP2 and PPARdelta receptors in early steps of decidualization in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 1 / physiology
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 / physiology
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Decidua / drug effects*
  • Decidua / metabolism
  • Decidua / physiology
  • Dinoprostone / metabolism
  • Dinoprostone / physiology*
  • Epoprostenol / metabolism
  • Epoprostenol / physiology*
  • Female
  • Intramolecular Oxidoreductases / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Mice
  • Mineral Oil / pharmacology*
  • PPAR delta / metabolism
  • PPAR delta / physiology*
  • Prostaglandin-E Synthases
  • Pyrazoles / pharmacology
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E / physiology*
  • Receptors, Prostaglandin E, EP2 Subtype
  • Time Factors

Substances

  • Cyclooxygenase 2 Inhibitors
  • Membrane Proteins
  • PPAR delta
  • Ptger2 protein, mouse
  • Pyrazoles
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • SC 560
  • Mineral Oil
  • Epoprostenol
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Ptgs1 protein, mouse
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Ptges protein, mouse
  • Dinoprostone