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Mol. Hum. Reprod. Advance Access published online on December 4, 2008
Molecular Human Reproduction, 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

S. S. Brizzolara, MD

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

J. Killeen, MD

1319 Punahou Street, Department of Pathology, John A. Burns School of Medicine, University of Hawaii Honolulu, Hawaii 86824, USA

J. Urschitz, PhD

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

Corresponding author: Shawna S. BRIZZOLARA, MD, FACOG, 1319 Punahou Street #824, Honolulu, Hawaii, USA 96826, (808) 203-6539, unlisted home phone, Fax (808) 955-2174, Email: 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) 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 thirty-four 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 Quantitative PCR confirmed 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 comprised 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

Reprints will not be available.

We have no corporate or commercial affiliations.

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


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