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

Stephen G. Marx, Melissa J. Wentz, Lynette B. MacKay, Dietmar Schlembach, Holger Maul, Cordula Fittkow, Randal Given, Yurij Vedernikov, George Saade, Robert E. Garfield

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)623-639
Number of pages17
JournalJournal of Histochemistry and Cytochemistry
Volume54
Issue number6
DOIs
StatePublished - Jun 2006

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Nitric Oxide Synthase Type II
Cyclooxygenase 2
Cervix Uteri
Progesterone
Collagen
Premature Obstetric Labor
Messenger RNA
Cervical Ripening
Pregnancy
Parturition
Prolonged Pregnancy
Birefringence
Estrus
Vascular Smooth Muscle
Prostaglandins
Smooth Muscle
Sprague Dawley Rats
Nitric Oxide
Epithelium
Immunohistochemistry

Keywords

  • Cervical ripening
  • Cervix
  • COX-2
  • iNOS
  • Nitric oxide
  • Onapristone
  • Parturition
  • Progesterone
  • Prostaglandin
  • Rat

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Marx, S. G., Wentz, M. J., MacKay, L. B., Schlembach, D., Maul, H., Fittkow, C., ... Garfield, R. E. (2006). Effects of progesterone on iNOS, COX-2 and collagen expression in the cervix. Journal of Histochemistry and Cytochemistry, 54(6), 623-639. https://doi.org/10.1369/jhc.5A6759.2006

Effects of progesterone on iNOS, COX-2 and collagen expression in the cervix. / Marx, Stephen G.; Wentz, Melissa J.; MacKay, Lynette B.; Schlembach, Dietmar; Maul, Holger; Fittkow, Cordula; Given, Randal; Vedernikov, Yurij; Saade, George; Garfield, Robert E.

In: Journal of Histochemistry and Cytochemistry, Vol. 54, No. 6, 06.2006, p. 623-639.

Research output: Contribution to journalArticle

Marx, SG, Wentz, MJ, MacKay, LB, Schlembach, D, Maul, H, Fittkow, C, Given, R, Vedernikov, Y, Saade, G & Garfield, RE 2006, 'Effects of progesterone on iNOS, COX-2 and collagen expression in the cervix', Journal of Histochemistry and Cytochemistry, vol. 54, no. 6, pp. 623-639. https://doi.org/10.1369/jhc.5A6759.2006
Marx, Stephen G. ; Wentz, Melissa J. ; MacKay, Lynette B. ; Schlembach, Dietmar ; Maul, Holger ; Fittkow, Cordula ; Given, Randal ; Vedernikov, Yurij ; Saade, George ; Garfield, Robert E. / Effects of progesterone on iNOS, COX-2 and collagen expression in the cervix. In: Journal of Histochemistry and Cytochemistry. 2006 ; Vol. 54, No. 6. pp. 623-639.
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