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Mol. Hum. Reprod. Advance Access originally published online on February 27, 2009
Molecular Human Reproduction 2009 15(4):251-257; 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 Söderberg1,2,4, Birgitta Byström1, Sebastian Kalamajski3, Anders Malmström3 and Gunvor Ekman-Ordeberg1

1Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital Solna, Södersjukhuset, S-171 76 Stockholm, Sweden 2Department 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

4 Corresponding author. Tel: +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 (POP). Collagens 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 post-menopausal, with POP. Real-time reverse transcription–polymerase chain reaction and immunohistochemistry for collagen I, collagen III, fibrillin-1, fibulin-5, decorin, lumican and fibromodulin were performed and compared with 14 controls, 8 pre- and 6 post-menopausal. 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, were discovered in premenopausal POP compared with matched controls. In all women with POP, there were lower gene expressions of fibromodulin, P = 0.004, and fibulin-5, P = 0.001, compared with all controls. All proteins were detectable by immunohistochemistry, showing a weaker staining for decorin in premenopausal 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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