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Differential expression of fibulins in the uterosacral ligaments of women with uterine prolapse

  • General Gynecology
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Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To compare fibulin-3 (FIB-3) and fibulin-5 (FIB-5) expressions in uterosacral ligaments (USL) of women with and without uterine prolapse.

Study design

USL were sampled in a standardized fashion from women with (n = 8) or without (n = 8) uterine prolapse. Quantitative Real-Time PCR was performed to measure mRNA and immunohistochemistry to assess protein expression.

Results

FIB-3 mRNA expression and FIB-3 staining intensity was similar in the USL of women with and without uterine prolapse {[(FIB-3 mean ± SD mRNA relative units) 0.45 ± 0.41 vs. 0.46 ± 0.82, NS] and [Intensity score, median (range), 1(0–1) vs. 1(0–1), NS]}. Both FIB-5 mRNA expression and FIB-5 staining intensity was significantly decreased in USL from women with uterine prolapse compared to women without prolapse {[(FIB-5 mean ± SD mRNA relative units) 0.07 ± 0.02 vs. 0.26 ± 0.20, P = 0.02] and [Intensity score, median (range), 0(0–2) vs. 3(2–3), P = 0.002]}.

Conclusion

FIB-5 expression is decreased in USL of women with uterine prolapse.

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References

  1. Nygaard I et al (2008) Prevalence of symptomatic pelvic floor disorders in US women. JAMA 300:1311–1316

    Article  CAS  PubMed  Google Scholar 

  2. Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL (1997) Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 89:501–506

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Smith AR, Hosker GL, Warrell DW (1989) The role of partial denervation of the pelvic floor in the aetiology of genitourinary prolapse and stress incontinence of urine. A neurophysiological study. Br J Obstet Gynaecol 96:24–28

    CAS  PubMed  Google Scholar 

  5. DeLancey JO (1992) Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 166:1717–1724 (discussion 1724-8)

    CAS  PubMed  Google Scholar 

  6. Buller JL, Thompson JR, Cundiff GW, Krueger Sullivan L, Schon Ybarra MA, Bent AE (2001) Uterosacral ligament: description of anatomic relationships to optimize surgical safety. Obstet Gynecol 97:873–879

    Article  CAS  PubMed  Google Scholar 

  7. Takacs P, Nassiri M, Gualtieri M, Candiotti K, Medina C (2008) Uterosacral ligament smooth muscle cell apoptosis is increased in women with uterine prolapse. Reprod Sci 16:447–452

    Google Scholar 

  8. Rahn DD, Ruff MD, Brown SA, Tibbals HF, Word RA (2008) Biomechanical properties of the vaginal wall: effect of pregnancy, elastic fiber deficiency, and pelvic organ prolapse. Am J Obstet Gynecol 198:590, e591–e596

    Google Scholar 

  9. Liu X, Zhao Y, Pawlyk B, Damaser M, Li T (2006) Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am J Pathol 168:519–528

    Article  CAS  PubMed  Google Scholar 

  10. Rahn DD et al (2009) Failure of pelvic organ support in mice deficient in fibulin-3. Am J Pathol 174:206–215

    Article  CAS  PubMed  Google Scholar 

  11. McLaughlin PJ et al (2007) Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. Hum Mol Genet 16:3059–3070

    Article  CAS  PubMed  Google Scholar 

  12. Drewes PG et al (2007) Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am J Pathol 170:578–589

    Article  CAS  PubMed  Google Scholar 

  13. Hirai M et al (2007) Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. J Cell Biol 176:1061–1071

    Article  CAS  PubMed  Google Scholar 

  14. Timpl R, Sasaki T, Kostka G, Chu ML (2003) Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol 4:479–489

    Article  CAS  PubMed  Google Scholar 

  15. Gallagher WM, Currid CA, Whelan LC (2005) Fibulins and cancer: friend or foe? Trends Mol Med 11:336–340

    Article  CAS  PubMed  Google Scholar 

  16. Chu ML, Tsuda T (2004) Fibulins in development and heritable disease. Birth Defects Res C Embryo Today 72:25–36

    Article  CAS  PubMed  Google Scholar 

  17. Schiemann WP, Blobe GC, Kalume DE, Pandey A, Lodish HF (2002) Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades. J Biol Chem 277:27367–27377

    Article  CAS  PubMed  Google Scholar 

  18. Nakamura T et al (2002) Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415:171–175

    Article  CAS  PubMed  Google Scholar 

  19. Stone EM et al (1999) A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nat Genet 22:199–202

    Article  CAS  PubMed  Google Scholar 

  20. Elahi E et al (2006) Homozygous missense mutation in fibulin-5 in an Iranian autosoma recessive cutis laxa pedigree and associated haplotype. J Invest Dermatol 126:1506–1509

    Article  CAS  PubMed  Google Scholar 

  21. Hu Q et al (2006) Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa. Hum Mol Genet 15:3379–3386

    Article  CAS  PubMed  Google Scholar 

  22. Paladini D et al (2007) Association of cutis laxa and genital prolapse: a case report. Int Urogynecol J Pelvic Floor Dysfunct 18:1367–1370

    Article  PubMed  Google Scholar 

  23. Bump RC et al (1996) The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 175:10–17

    Article  CAS  PubMed  Google Scholar 

  24. Bai SW, Jung YW, Kwon HS et al (2004) The role of estrogen receptor, progesterone receptor and p53 in development of stress urinary incontinence. Yonsei Med J 45:885–890

    CAS  PubMed  Google Scholar 

  25. Vincek V, Nassiri M, Nadji M, Morales A (2003) A tissue fixative that protects macromolecules (DNA, RNA, and protein) and histomorphology in clinical samples. Lab Invest 83:1427–1435

    Article  CAS  PubMed  Google Scholar 

  26. Klutke J et al (2008) Decreased endopelvic fascia elastin content in uterine prolapse. Acta Obstet Gynecol Scand 87:111–115

    Article  CAS  PubMed  Google Scholar 

  27. Takacs P, Nassiri M, Viciana A, Candiotti K, Fornoni A, Medina CA (2009) Fibulin-5 expression is decreased in women with anterior vaginal wall prolapse. Int Urogynecol J Pelvic Floor Dysfunct 20:207–211

    Article  PubMed  Google Scholar 

  28. Jung HJ, Jeon MJ, Yim GW, Kim SK, Choi JR, Bai SW (2009) Changes in expression of fibulin-5 and lysyl oxidase-like 1 associated with pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol 145:117–122

    Article  CAS  PubMed  Google Scholar 

  29. Soderberg MW, Bystrom B, Kalamajski S, Malmstrom A, Ekman-Ordeberg G (2009) Gene expressions of small leucine-rich repeat proteoglycans and fibulin-5 are decreased in pelvic organ prolapse. Mol Hum Reprod 15:251–257

    Article  PubMed  Google Scholar 

  30. Swartz MA, Tschumperlin DJ, Kamm RD, Drazen JM (2001) Mechanical stress is communicated between different cell types to elicit matrix remodeling. Proc Natl Acad Sci USA 98:6180–6185

    Article  CAS  PubMed  Google Scholar 

  31. Kuang PP, Goldstein RH, Liu Y, Rishikof DC, Jean JC, Joyce-Brady M (2003) Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair. Am J Physiol Lung Cell Mol Physiol 285:L1147–L1152

    CAS  PubMed  Google Scholar 

  32. Wieslander CK, Acevedo JF, Drewes PG, Yanagisawa HK, Word RA (2006) Pelvic organ prolapse severity increases with age in fibulin-5 knockout mice. Int Urogynecol J 17:S371–S372

    Google Scholar 

  33. Man WC, Ho JY, Wen Y, Sokol ER, Polan ML, Chen B (2009) Is lysyl oxidase-like protein-1, alpha-1 antitrypsin, and neutrophil elastase site specific in pelvic organ prolapse? Int Urogynecol J Pelvic Floor Dysfunct. 2009 Sep 10. [Epub ahead of print]

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Conflict of interest statement

The authors do not have any conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology (D-50), Miller School of Medicine, Jackson Memorial Hospital, University of Miami, P.O. Box 016960, Miami, FL, 33010, USA

    Peter Takacs, Sujata Yavagal & Carlos A. Medina

  2. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Mehdi Nassiri

  3. Department of Anesthesiology, Miller School of Medicine, University of Miami, Miami, FL, USA

    Keith Candiotti & Jinfeng Yang

Authors
  1. Peter Takacs
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  2. Mehdi Nassiri
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  3. Keith Candiotti
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  4. Jinfeng Yang
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  5. Sujata Yavagal
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  6. Carlos A. Medina
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Correspondence to Peter Takacs.

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Takacs, P., Nassiri, M., Candiotti, K. et al. Differential expression of fibulins in the uterosacral ligaments of women with uterine prolapse. Arch Gynecol Obstet 282, 389–394 (2010). https://doi.org/10.1007/s00404-009-1262-2

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  • DOI: https://doi.org/10.1007/s00404-009-1262-2

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