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Mol. Hum. Reprod. Advance Access published online on February 27, 2009
Molecular Human Reproduction, doi:10.1093/molehr/gap011
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© The Author 2009. 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 Expressions of Small Leucine-rich Repeat Proteoglycans and Fibulin-5 are Decreased in Pelvic Organ Prolapse

Marie Westergren Söderberg, M.D.1,2, Birgitta Byström, Lab. Engineer1, Sebastian Kalamajski, Ph.D.3, Anders Malmström, Ph.D.3 and Gunvor Ekman-Ordeberg, M.D., Ph.D.1

1Departments of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden 2Departments of Obstetrics and Gynecology, Karolinska Institutet, Stockholm South Hospital, S-118 83 Stockholm, Sweden 3Department of Experimental Medical Science, BMC, Lund University, S-221 84 Lund, Sweden

Corresponding author: Marie Westergren Söderberg, Department of Obstetrics and Gynecology, Södersjukhuset, S-118 83 Stockholm, Sweden. Telephone: +46 73 9625479. E-mail: marie.westergren-soderberg{at}sodersjukhuset.se

Few studies are performed on the sustainability of the pelvic floor extracellular matrix important for preventing development of pelvic organ prolapse . Collagen I and III, the elastin associated proteins fibrillin-1 and fibulin-5 and the small leucine-rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Para-urethral biopsies were obtained from 15 women, 6 pre- and 9 postmenopausal, with POP. Real-time RT-PCR and immunohistochemistry for collagen I, collagen III, fibrillin-1, fibulin-5, decorin, lumican and fibromodulin was performed and compared to 14 controls, 8 pre- and 6 postmenopausals. Statistical comparisons controlled for age changes in gene expressions. A 16-fold decrease in decorin mRNA expression, p=0.0001 and 8-fold in lumican mRNA expression, p=0.001, was discovered in premenopausal POP compared to matched controls. In all women with POP there were lower gene expressions of fibromodulin, p=0.004 and fibulin-5, p=0.001, compared to all controls. All proteins were detectable by immunohistochemistry, showing a weaker staining for decorin in pre-menopausal POP. For the first time we show substantially decreased gene signal for production of SLRPs, regulators of collagen fiber assembly and impairment in elastic fiber assembly by down-regulation of fibulin-5 in POP.

Key Words: prolapse/proteoglycan/elastin/collagen/extracellular matrix

Submitted on August 10, 2008; resubmitted on January 30, 2009; accepted on February 10, 2009.


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