International Urogynecology Journal

, Volume 21, Issue 11, pp 1397–1404 | Cite as

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

  • May Alarab
  • Maria AT Bortolini
  • Harold Drutz
  • Stephen Lye
  • Oksana Shynlova
Original Article


Introduction and Hypothesis

The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle.


Total mRNAs and proteins extracted from the vaginal tissue were examined by real-time polymerase chain reaction and immunoblotting, and tissue specimens were analyzed by immunohistochemistry.


The expression of LOX, LOXL1, and LOXL3 genes as well as LOX and LOXL3 proteins were significantly reduced in POP patients (P < 0.05). Immunolocalization of LOX family proteins was confirmed in all vaginal specimens.


We proposed that reduced expression of LOX enzymes may result in defective assembly of pelvic tissues and development of POP.


ECM LOX enzymes POP Premenopausal Vagina 



The study funding was provided by the Research Fund, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto. There is no conflict of interest to be disclosed.

We thank Dr. V. Miranda for assisting us in the statistical analysis.

Conflicts of interest


Supplementary material

192_2010_1199_Fig4_ESM.gif (22 kb)
Supplemental Fig. 1

Double immunostaining for CD68 and LOXL1 proteins. Immunofluorescence microscopy stained with antibodies against LOXL1 (C, red color), CD68 (B, green color), and nuclear staining (A, blue color). Coexpression of LOXL1 and CD68 by the same cell is indicated by yellow color (overlap of green and red). Magnification is ×400; scale bar = 25 μm (GIF 22 kb)


  1. 1.
    Hendrix SL, Clark A, Nygaaard I et al (2002) Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity. Am J Obstet Gynecol 186:1160–1166CrossRefPubMedGoogle Scholar
  2. 2.
    Luber KM, Boero S, Choe JY (2001) The demographics of pelvic floor disorders: current observations and future projections. Am J Obstet Gynecol 184:1496–1501CrossRefPubMedGoogle Scholar
  3. 3.
    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 Gynecol 96:24–28Google Scholar
  4. 4.
    Swift SE, Tate SB, Nicholas J (2003) Correlation of symptoms with degree of pelvic organ support in a general population of women: what is pelvic organ prolapse? Am J Obstet Gynecol 198:372–377CrossRefGoogle Scholar
  5. 5.
    Moalli PA, Jones Ivy S, Meyn LA, Zyczynski HM (2003R) Risk factors associated with pelvic floor disorders in women undergoing surgical repair. Obstet Gynecol 101:869–874CrossRefGoogle Scholar
  6. 6.
    Harris RL, Cundiff GW, Coates KW, Bump RC (1998) Urinary incontinence and pelvic organ Prolapse in nulliparous women. Obstet Gynecol 92:951–954CrossRefPubMedGoogle Scholar
  7. 7.
    O'Boyle AL, Woodman PJ, O'Boyle JD, Davis GD, Swift SE (2002) Pelvic organ support in nulliparous and nonpregnant women: a case control study. Am J Obstet Gynecol 187:99–102CrossRefPubMedGoogle Scholar
  8. 8.
    Norton P, Baker J, Sharp H, Warenski J (1995) Genitourinary prolapse and joint mobility in women. Obstet Gynecol 85(2):225–228CrossRefPubMedGoogle Scholar
  9. 9.
    Carley ME, Schaffer J (2000) Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers Danlos syndrome. Am J ObstetGynecol 182(5):1021–1023CrossRefGoogle Scholar
  10. 10.
    Chen BH, Wen Y, Polan ML (2004) Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse. Neurourol Urodyn 23:119–126CrossRefPubMedGoogle Scholar
  11. 11.
    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(2):519–528CrossRefPubMedGoogle Scholar
  12. 12.
    Kobak W, Lu J, Hardart A, Zhang C, Stanczyk F, Felix JC (2005) Expression of lysyl oxidase and transforming growth factor B2 in women with severe pelvic organ prolapse. J Rep Med 50(11):827–831Google Scholar
  13. 13.
    Zhang SQ, Zhang LL, Yu H (2008) Expression of elastin, lysyl oxidase and elafin in the cardinal ligament of women with pelvic organ prolapse. Zhonghua Fu Chan Ke Za Zhi 43(9):675–679PubMedGoogle Scholar
  14. 14.
    Kagan HM, Li W (2003) Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem 88:660–672CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang H, Hu W, Ramirez F (1995) Developmental expression of fibrillin genes suggests heterogeneity of extra-cellular microfibrils. J Cell Biol 129:1165–1176CrossRefPubMedGoogle Scholar
  16. 16.
    Nakamura T, Lozano P, Ikeda Y et al (2002) Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415:171–175CrossRefPubMedGoogle Scholar
  17. 17.
    Phillips C, Anthony F, Benyon C, Monga A (2006) Collagen metabolism in uterosacral ligaments and vaginal skin of women with uterine prolapse. Br J Obstet Gynecol 113:39–46Google Scholar
  18. 18.
    Chen B, Wen Y, Zhang Z, Guo Y, Warrington JA, Polan ML (2006) Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women. Hum Reprod 21(1):22–29CrossRefPubMedGoogle Scholar
  19. 19.
    Bump RC, Mattiasson A, Bo K et al (1996) The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 175:10–17CrossRefPubMedGoogle Scholar
  20. 20.
    Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA (2002) Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol 187(1):56–63CrossRefPubMedGoogle Scholar
  21. 21.
    Miller M, Vadachkoria S, Luthy DA, Williams MA (2005) Evaluation of housekeeping genes in placental comparative expression studies. Placenta 26:601–607CrossRefGoogle Scholar
  22. 22.
    Vandesompele J, De Preter K, Pattyn F et al (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):34CrossRefGoogle Scholar
  23. 23.
    Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108CrossRefPubMedGoogle Scholar
  24. 24.
    Chen B, Wen Y, Zhang Z, Wang H, Warrington JA, Polan ML (2003) Menstrual phase-dependent gene expression differences in periurethral vaginal tissue from women with stress incontinence. Am J Obstet Gynecol 189(1):89–97CrossRefPubMedGoogle Scholar
  25. 25.
    Görögh T, Weise JB, Holtmeier C et al (2007) Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma. J Pathol 212(1):74–82CrossRefPubMedGoogle Scholar
  26. 26.
    Lee JE, Kim Y (2006) A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity. J Biol Chem 281(49):37282–37290CrossRefPubMedGoogle Scholar
  27. 27.
    Borel A, Eichenberger D, Farjanel J et al (2001) Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1. J Biol Chem 276(52):48944–48949CrossRefPubMedGoogle Scholar
  28. 28.
    Thomassin L, Werneck CC, Broekelmann TJ et al (2005) The pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. J Biol Chem 280(52):42848–42855CrossRefPubMedGoogle Scholar
  29. 29.
    Shanley CJ, Gharaee-Kermani M, Sarkar R, Welling TH, Kriegel A, Ford JW, Stanley JC, Phan SH (1997) Transforming growth factor-beta 1 increases lysyl oxidase enzyme activity and mRNA in rat aortic smooth muscle cells. J Vasc Surg 25(3):446–452CrossRefPubMedGoogle Scholar
  30. 30.
    Nellaiappan K, Risitano A, Liu G, Nicklas G, Kagan HM (2000) Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells. J Cell Biochem 79:576–582CrossRefPubMedGoogle Scholar

Copyright information

© The International Urogynecological Association 2010

Authors and Affiliations

  • May Alarab
    • 1
    • 2
    • 3
  • Maria AT Bortolini
    • 1
    • 2
  • Harold Drutz
    • 1
    • 2
  • Stephen Lye
    • 2
    • 3
  • Oksana Shynlova
    • 3
  1. 1.Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and GynecologyMount Sinai Hospital, University of TorontoTorontoCanada
  2. 2.Department of Obstetrics and GynecologyUniversity of TorontoTorontoCanada
  3. 3.Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada

Personalised recommendations