Gene Expression and Immunoreactivity of Elastolytic Enzymes in the Uterosacral Ligaments From Women With Uterine Prolapse


Altered elastin metabolism has been documented in pelvic tissues from women with pelvic floor dysfunction. This study was conducted to quantify the expression of elastolytic enzymes in uterine cervix and uterosacral ligaments from women with uterine prolapse compared to asymptomatic normal controls. Paired tissues of uterosacral ligament and cervical tissues were obtained from 27 women with uterine prolapse and 14 normal controls. Steady state of matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinase 2 (TIMP-2), neutrophil elastase, α-1 antitrypsin immunoreactivity, and messenger RNA (mRNA) expression were analyzed by immunohistochemistry and real-time polymerase chain reaction, respectively. When compared with controls, women with uterine prolapse had a significantly greater level of MMP-2 immunoreactivity and mRNA expression, but less TIMP-2 and α-1 antitrypsin immunoreactivity and mRNA expression in their uterosacral ligaments. However, neutrophil elastase mRNA expression was similar between uterine prolapse and control tissue. Our results showed that there was a close relationship between expressions of MMP-2, TIMP-2, and α-1 antitrypsin in uterosacral ligament and the occurrence of uterine prolapse.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 510

This is the net price. Taxes to be calculated in checkout.


  1. 1.

    DeLancey JOL. Anatomy and biomechanics of genital prolapse. Clin Obstet Gynecol. 1993;36(4):897–909.

  2. 2.

    Vrhovski B, Weiss AS. Biochemistry of tropoelastin. Eur J Biochem. 1998;258(1):1–18.

  3. 3.

    Yamamoto K, Yamamoto M, Akazawa K, Tajima S, Wakimoto H, Aoyagi M. Decrease in elastin gene expression and protein synthesis in fibroblasts derived from cardinal ligaments of patients with prolapsus uteri. Cell Biol Int. 1997;21(9):605–611.

  4. 4.

    Chen BH, Wen Y, Polan ML. Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse. Neurourol Urodyn. 2004:23(2):119–126.

  5. 5.

    Werb Z, Banda MJ, McKerrow JH, Sandhaus RA. Elastases and elastin degradation. J Invest Dermatol. 1982;79(suppl 1): 154S–159S.

  6. 6.

    Jensen SA, Andersen P, Vrhovski B, Weiss AS. Rational design of tropoelastin peptide-based inhibitors of metalloproteinases. Arch Biochem Biophys. 2003;409(2):335–340.

  7. 7.

    Chen B, Wen Y, Yu X, Polan ML. The role of neutrophil elastase in elastin metabolism of pelvic tissues from women with stress urinary incontinence. Neurourol Urodyn. 2007;26(2):274–279.

  8. 8.

    Bump RC, Mattiasson A, Bø K, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol. 1996;175(1):10–17.

  9. 9.

    Liang CC, Chang YL, Chang SD, Lo TS, Soong YK. Pessary test to predict post-operative urinary incontinence in women undergoing hysterectomy for prolapse. Obstet Gynecol. 2004;104(4):795–800.

  10. 10.

    Chen BH, Wen Y, Li H, Polan ML. Collagen metabolism and turnover in women with stress urinary incontinence and pelvic prolapse. Int Urogynecol J. 2002;13(2):80–87.

  11. 11.

    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–408.

  12. 12.

    Song Y, Hong X, Yu Y, Lin Y. Changes of collagen type III and decorin in paraurethral connective tissue from women with stress urinary incontinence and prolapse. Int Urogynecol J. 2007;18:1459–1463.

  13. 13.

    Liang CC, Ro LS, Lee TH. Effects of pelvic nerve neurectomy and estrogen on the M2 muscarinic receptor of the urinary bladder. Chang Gung Med J. 2005;28:786–793.

  14. 14.

    Chen B, Wen Y, Yu X, Polan ML. Elastin metabolism in pelvic tissues: Is it modulated by reproductive hormones? Am J Obstet Gynecol. 2005;192(5):1605–1613.

  15. 15.

    Philips CH, Anthony F, Benyon C, Monga A. Collagen metabolism in the uterosacral ligaments and vaginal skin of women with uterine prolapse. BJOG. 2006;113(1):39–46.

  16. 16.

    Budatha M, Roshanravan S, Zheng Q, et al. Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest. 2011;121(5):2048–2059.

  17. 17.

    Gabriel B, Watermann D, Hancke K, et al. Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2006;17(5):478–482.

  18. 18.

    Ewies AA, Al-Azzawi F, Thompson J. Changes in extracellular matrix proteins in the cardinal ligaments of post-menopausal women with or without prolapse: a computerized immunohisto-morphometric analysis. Human Reprod. 2003;18(10):2189–2195.

  19. 19.

    Karam JA, Vazquez DV, Lin VK, Zimmern PE. Elastin expression and elastic fiber width in the anterior vaginal wall of postmenopausal women with and without prolapse. BJU Int. 2007;100(2):346–350.

  20. 20.

    Lin SY, Tee YT, Ng SC, Chang H, Lin P, Chen GD. Changes in the extracellular matrix in the anterior vagina of women with or without prolapse. Int Urogynecol J. 2007;18(1):43–48.

  21. 21.

    Klutke J, Ji Q, Campeau J, et al. Decreased endopelvic fascia elastin content in uterine prolapse. Acta Obstet Gynecol. 2008;87(1):111–115.

Download references

Author information

Correspondence to Hong-Yuan Huang MD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liang, C., Huang, H. & Chang, S. Gene Expression and Immunoreactivity of Elastolytic Enzymes in the Uterosacral Ligaments From Women With Uterine Prolapse. Reprod. Sci. 19, 354–359 (2012).

Download citation


  • antitrypsin
  • elastin
  • metalloproteinase
  • uterine prolapse