Effects of progesterone on iNOS, COX-2, and collagen expression in the cervix

J Histochem Cytochem. 2006 Jun;54(6):623-39. doi: 10.1369/jhc.5A6759.2006. Epub 2006 Jan 6.

Abstract

This study examines the relationship between inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the control of cervical ripening and parturition under normal (normal term pregnancy) and abnormal (preterm labor and prolongation of pregnancy) conditions by (a) measuring changes in the collagen both visually and quantitatively, (b) localizing and characterizing iNOS and COX-2 under normal conditions, and (c) characterizing the changes in iNOS and COX-2 under abnormal conditions. Cervices are obtained from estrus and timed pregnant Sprague-Dawley rats (n=4-10 per group). Preterm labor is induced with Onapristone (3 mg/rat; progesterone antagonist) and the prolongation of pregnancy with progesterone (2.5 mg, twice daily). Collagen changes are measured and visualized with the picrosirius polarization method. RT-PCR is used to characterize the mRNA expression (p<0.05), and immunohistochemistry is used to localize the protein expression for iNOS and COX-2. The organization and birefringence of the collagen during pregnancy decreased and is supported by changes in the luminosity (p<0.001). The iNOS and COX-2 enzymes were localized in cervical smooth muscle, vascular smooth muscle, and epithelium. Under normal conditions, iNOS mRNA levels decreased as COX-2 mRNA levels increased demonstrating an inverse correlation (Spearman r = -0.497; p=0.00295). Onapristone stimulated preterm labor, increasing the iNOS and COX-2 mRNA (p<0.05). The increase demonstrated a positive correlation (Spearman r = 0.456; p=0.03). Progesterone prolonged pregnancy, decreasing the iNOS and COX-2 mRNA (p=0.036). In conclusion, there may be an interaction between the nitric oxide and prostaglandin pathways in cervical ripening and parturition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Azo Compounds
  • Cervical Ripening / drug effects
  • Cervical Ripening / metabolism
  • Cervix Uteri / drug effects*
  • Cervix Uteri / metabolism
  • Collagen / biosynthesis*
  • Collagen / genetics
  • Coloring Agents
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • Female
  • Gonanes / pharmacology
  • Immunohistochemistry
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Nitric Oxide Synthase Type II / genetics
  • Obstetric Labor, Premature / chemically induced
  • Obstetric Labor, Premature / metabolism
  • Organ Specificity
  • Parturition / drug effects
  • Parturition / metabolism
  • Pregnancy
  • Pregnancy, Prolonged / chemically induced
  • Pregnancy, Prolonged / metabolism
  • Progesterone / antagonists & inhibitors
  • Progesterone / pharmacology*
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Azo Compounds
  • Coloring Agents
  • Gonanes
  • RNA, Messenger
  • C.I. direct red 80
  • Progesterone
  • Collagen
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • onapristone