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Mol. Hum. Reprod. Advance Access originally published online on December 4, 2008
Molecular Human Reproduction 2009 15(1):59-67; doi:10.1093/molehr/gan074
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Gene expression profile in pelvic organ prolapse{dagger}

S.S. Brizzolara1,3, J. Killeen2 and J. Urschitz1

1Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, 1319 Punahou Street #824, Honolulu, HI 96826, USA 2Department of Pathology, John A. Burns School of Medicine, University of Hawaii, 1319 Punahou Street, Hawaii, HI 86824, USA

3 Correspondence address. Fax: +1-808-955-2174; E-mail: brizzola{at}hawaii.edu

It was hypothesized that the processes contributing to pelvic organ prolapse (POP) may be identified by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. In order to test this, we performed a frequency-matched case–control study of women undergoing hysterectomy for POP and controls. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32 878 genes. Significance Analysis of Microarrays (Stanford University, CA, USA) identified differentially expressed genes used for ontoanalysis. Quantitative PCR (qPCR) confirmed results. Light microscopy confirmed the tissue type and assessed inflammatory infiltration. The analysis of 34 arrays revealed 249 differentially expressed genes with fold changes (FC) larger than 1.5 and false discovery rates ≤5.2%. Immunity and defense was the most significant biological process differentially expressed in POP. qPCR confirmed the elevated steady-state mRNA levels for four genes: interleukin-6 (FC 9.8), thrombospondin 1 (FC 3.5) and prostaglandin-endoperoxide synthase 2 (FC 2.4) and activating transcription factor 3 (FC 2.6). Light microscopy showed all the samples were composed of fibromuscular connective tissue with no inflammatory infiltrates. In conclusion, genes enriched for ‘immunity and defense’ contribute to POP independent of inflammatory infiltrates.

Key words: connective tissue/gene expression/ontoanalysis/pelvic organ prolapse/transcription profiling

{dagger} This was previously presented at the American Urogynecologic Society's annual meeting, 17 October 2006, Palm Springs, CA, USA.

Submitted on September 21, 2008; resubmitted on November 22, 2008; accepted on November 30, 2008.


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