Reproductive Sciences

, Volume 19, Issue 4, pp 354–359 | Cite as

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

  • Ching-Chung Liang
  • Hong-Yuan HuangEmail author
  • Shuenn-Dhy Chang
Original Articles


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.


antitrypsin elastin metalloproteinase uterine prolapse 


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  1. 1.
    DeLancey JOL. Anatomy and biomechanics of genital prolapse. Clin Obstet Gynecol. 1993;36(4):897–909.CrossRefGoogle Scholar
  2. 2.
    Vrhovski B, Weiss AS. Biochemistry of tropoelastin. Eur J Biochem. 1998;258(1):1–18.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  5. 5.
    Werb Z, Banda MJ, McKerrow JH, Sandhaus RA. Elastases and elastin degradation. J Invest Dermatol. 1982;79(suppl 1): 154S–159S.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.PubMedGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar
  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.CrossRefGoogle Scholar

Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Ching-Chung Liang
    • 1
    • 2
  • Hong-Yuan Huang
    • 1
    • 2
    Email author
  • Shuenn-Dhy Chang
    • 1
    • 2
  1. 1.Department of Obstetrics and GynecologyChang Gung Memorial Hospital, Linkou Medical CenterTao-YuanTaiwan
  2. 2.College of MedicineChang Gung UniversityTaoyuanTaiwan

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