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Estrogen-related genome-based expression profiling study of uterosacral ligaments in women with pelvic organ prolapse

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Abstract

Introduction and hypothesis

The aim of the study was to identify the differential expression of estrogen-related genes that may be involved in the menopause and pelvic organ prolapse (POP) using microarray analysis.

Methods

An age, parity, and menopausal status-matched case–control study with 12 POP patients and 5 non-POP patients was carried out. The study was conducted from January to December 2010 at Yonsei University, Severance Hospital. We examined microarray gene expression profiles in uterosacral ligaments (USLs) from POP and non-POP patients. Total RNA was extracted from USL samples to generate labeled cDNA, which was hybridized to microarrays and analyzed for the expression of 44,049 genes. We identified differentially expressed genes and performed functional clustering. After clustering, we focused on transcriptional response and signal transduction gene clusters, which are associated with estrogen, and then validated the changes of gene expression levels observed with the microarray analysis using quantitative polymerase chain reaction (qPCR).

Results

The data from the microarray analysis using more than a 1.5-fold change with p value <0.05 resulted in 143 upregulated genes and 87 downregulated genes. Of 59 genes identified to be associated with signal transduction and transcription, 4 genes were chosen for qPCR that have been classified to be associated with estrogen. We found that estrogen receptor-related receptor-α (ERRα) was downregulated and that the expression of death-associated protein kinase 2 (DAPK 2), signal-transducing adaptor protein-2 (STAP-2), and interleukin (IL)-15 were upregulated.

Conclusions

We found four differentially expressed genes by microarray analysis that may account for the way in which changes in estrogen level affect POP pathophysiology.

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References

  1. Wu JM, Hundley AF, Fulton RG, Myers ER (2009) Forecasting the prevalence of pelvic floor disorders in U.S. women: 2010 to 2050. Obstet Gynecol 114(6):1278–1283

    Article  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(4):501–506

    Article  PubMed  CAS  Google Scholar 

  3. Jelovsek JE, Maher C, Barber MD (2007) Pelvic organ prolapse. Lancet 369(9566):1027–1038

    Article  PubMed  Google Scholar 

  4. DeLancey JO (1992) Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 166(6 Pt 1):1717–1724, discussion 1724–1718

    Article  PubMed  CAS  Google Scholar 

  5. Moon YJ, Choi JR, Jeon MJ, Kim SK, Bai SW (2011) Alteration of elastin metabolism in women with pelvic organ prolapse. J Urol 185(5):1786–1792

    Article  PubMed  CAS  Google Scholar 

  6. Suzme R, Yalcin O, Gurdol F, Gungor F, Bilir A (2007) Connective tissue alterations in women with pelvic organ prolapse and urinary incontinence. Acta Obstet Gynecol Scand 86(7):882–888

    Article  PubMed  CAS  Google Scholar 

  7. Sze EH, Hobbs G (2012) A prospective cohort study of pelvic support changes among nulliparous, multiparous, and pre- and post-menopausal women. Eur J Obstet Gynecol Reprod Biol 160(2):232–235

    Article  PubMed  Google Scholar 

  8. Jackson S, James M, Abrams P (2002) The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence. BJOG 109(3):339–344

    Article  PubMed  CAS  Google Scholar 

  9. Hundley AF, Yuan L, Visco AG (2008) Gene expression in the rectus abdominus muscle of patients with and without pelvic organ prolapse. Am J Obstet Gynecol 198(2):220.e221–220.e227

    Article  Google Scholar 

  10. Brizzolara SS, Killeen J, Urschitz J (2009) Gene expression profile in pelvic organ prolapse. Mol Hum Reprod 15(1):59–67

    Article  PubMed  CAS  Google Scholar 

  11. Tseng LH, Chen I, Lin YH, Chen MY, Lo TS, Lee CL (2010) Genome-based expression profiles study for the pathogenesis of pelvic organ prolapse: an array of 33 genes model. Int Urogynecol J 21(1):79–84

    Article  PubMed  Google Scholar 

  12. Hendrix SL, Cochrane BB, Nygaard IE, Handa VL, Barnabei VM, Iglesia C et al (2005) Effects of estrogen with and without progestin on urinary incontinence. JAMA 293(8):935–948

    Article  PubMed  CAS  Google Scholar 

  13. Goldstein SR, Nanavati N (2002) Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Am J Obstet Gynecol 187(3):521–527

    Article  PubMed  CAS  Google Scholar 

  14. Chen H, Chung Y, Lin W, Chen W, Tsai F, Tsai C (2008) Estrogen receptor alpha polymorphism is associated with pelvic organ prolapse risk. Int Urogynecol J Pelvic Floor Dysfunct 19(8):1159–1163

    Article  PubMed  Google Scholar 

  15. Skala CE, Petry IB, Albrich S, Puhl A, Naumann G, Koelbl H (2011) The effect of genital and lower urinary tract symptoms on steroid receptor expression in women with genital prolapse. Int Urogynecol J Pelvic Floor Dysfunct 22(6):705–712

    Article  Google Scholar 

  16. Bonnelye E, Aubin JE (2005) Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone. J Clin Endocrinol Metab 90(5):3115–3121

    Article  PubMed  CAS  Google Scholar 

  17. Bonnelye E, Merdad L, Kung V, Aubin JE (2001) The orphan nuclear estrogen receptor-related receptor alpha (ERRalpha) is expressed throughout osteoblast differentiation and regulates bone formation in vitro. J Cell Biol 153(5):971–984

    Article  PubMed  CAS  Google Scholar 

  18. Verma S, Hiby SE, Loke YW, King A (2000) Human decidual natural killer cells express the receptor for and respond to the cytokine interleukin 15. Biol Reprod 62(4):959–968

    Article  PubMed  CAS  Google Scholar 

  19. Chegini N, Ma C, Roberts M, Williams RS, Ripps BA (2002) Differential expression of interleukins (IL) IL-13 and IL-15 throughout the menstrual cycle in endometrium of normal fertile women and women with recurrent spontaneous abortion. J Reprod Immunol 56(1–2):93–110

    Article  PubMed  CAS  Google Scholar 

  20. Kitaya K, Yasuda J, Yagi I, Tada Y, Fushiki S, Honjo H (2000) IL-15 expression at human endometrium and decidua. Biol Reprod 63(3):683–687

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. Lin Y, Hupp TR, Stevens C (2010) Death-associated protein kinase (DAPK) and signal transduction: additional roles beyond cell death. FEBS J 277(1):48–57

    Article  PubMed  CAS  Google Scholar 

  23. Liu SB, Zhang N, Guo YY, Zhao R, Shi TY, Feng SF et al (2012) G-protein-coupled receptor 30 mediates rapid neuroprotective effects of estrogen via depression of NR2B-containing NMDA receptors. J Neurosci 32(14):4887–4900

    Article  PubMed  CAS  Google Scholar 

  24. Levy D, Plu-Bureau G, Decroix Y, Hugol D, Rostene W, Kimchi A et al (2004) Death-associated protein kinase loss of expression is a new marker for breast cancer prognosis. Clin Cancer Res 10(9):3124–3130

    Article  PubMed  CAS  Google Scholar 

  25. Tanaka T, Bai T, Yukawa K (2010) Death-associated protein kinase is essential for the survival of various types of uterine cancer cells. Int J Oncol 37(4):1017–1022

    Article  PubMed  CAS  Google Scholar 

  26. Takacs P, Nassiri M, Gualtieri M, Candiotti K, Medina CA (2009) Uterosacral ligament smooth muscle cell apoptosis is increased in women with uterine prolapse. Reprod Sci 16(5):447–452

    Article  PubMed  Google Scholar 

  27. Sekine Y, Ikeda O, Mizushima A, Ueno Y, Muromoto R, Yoshimura A et al (2012) STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis. Oncogene 31:(40)4384–4396

    Article  PubMed  CAS  Google Scholar 

  28. Ikeda O, Sekine Y, Mizushima A, Nakasuji M, Miyasaka Y, Yamamoto C et al (2010) Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. J Biol Chem 285(49):38093–38103

    Article  PubMed  CAS  Google Scholar 

  29. Visco AG, Yuan L (2003) Differential gene expression in pubococcygeus muscle from patients with pelvic organ prolapse. Am J Obstet Gynecol 189(1):102–112

    Article  PubMed  CAS  Google Scholar 

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Funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (2010–008482).

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seonsan-ro 250, Seodaemun-gu, Seoul, Korea, 120-749

    Yeo Jung Moon & Sang Wook Bai

  2. Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea

    Yeo Jung Moon & Chul Hoon Kim

  3. College of Medicine, Yonsei University, Seoul, Korea

    Chan-Young Jung

Authors
  1. Yeo Jung Moon
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  2. Sang Wook Bai
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  3. Chan-Young Jung
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Corresponding author

Correspondence to Sang Wook Bai.

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Moon, Y.J., Bai, S.W., Jung, CY. et al. Estrogen-related genome-based expression profiling study of uterosacral ligaments in women with pelvic organ prolapse. Int Urogynecol J 24, 1961–1967 (2013). https://doi.org/10.1007/s00192-013-2124-9

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  • DOI: https://doi.org/10.1007/s00192-013-2124-9

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