Studies on the extracellular matrix of the dysfunctional pelvic floor
Author: Söderberg, Marie Westergren
Date: 2008-12-12
Location: Skandiasalen, Astrid Lindgrens Barnsjukhus, Karolinska Universitetssjukhuset, Solna
Time: 09.00
Department: Institutionen för kvinnors och barns hälsa / Department of Women's and Children's Health
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thesis.pdf (4.193Mb)
Abstract
Objective: Pelvic floor dysfunction cause impaired quality of life of
many women and is one of the most common reasons for gynaecological
surgery on benign indications. Little is known about the pelvic floor
extracellular matrix as a pre-requisite for mechanical sustainability
through vaginal delivery, age and hormonal changes. For this reason,
pelvic floor extracellular matrix was investigated in women suffering
from the two major dysfunctional conditions, pelvic organ prolapse (POP )
and stress urinary incontinence (SUI), regarding molecules responsible
for tensile strength and elasticity.
Methods: Para-urethral biopsies were collected from women with POP , SUI and compared to healthy controls matched according to menopausal status or age. The collagen concentration and extractability by pepsin digestion were analyzed in women with POP . Real-time RT -PCR revealed the gene signals and immunohistochemistry the protein expressions of collagen I, collagen III , the small leucin-rich proteoglycans (SLRP s) decorin, lumican and fibromodulin as well as the elastin associated proteins fibrillin-1 and fibulin-5 in POP and SUI. In SUI the sex steroid hormone receptor isoforms and subtypes ER-alpha, ER-beta, PR-(A+B), PR-B and AR were identified and quantified by scoring and image analysis (ER-alpha and ER-beta) completed by mRNA expressions analyze of ER-alpha, ER-beta, PR and AR by real-time RT -PCR .
Results: The collagen concentration was 30 % lower in the pelvic floor ECM of women younger than 53 years suffering from POP . There were lower mRNA expressions of all the investigated SLRP s and the elastin associated fibulin-5 in pre-menopausal women with POP . A 16-fold reduction of decorin mRNA was most prominent with a corresponding weaker protein expression of decorin. Postmenopausal women with POP exposed significantly lower mRNA expressions of fibromodulin and fibulin-5. A significant reduction of the mRNA expression of fibrillin-1 seen in women with SUI irrespective of menopausal status was confirmed by a lower immunoreactivity. All hormone receptor isoforms or subtypes were expressed in the pelvic floor ECM with ER-beta showing an increased expression in pre-menopausal women with SUI. A corresponding elevation in gene expression was not discovered.
Conclusion: Evidence for POP and SUI deriving from different alterations in the pelvic floor ECM has been found. The results therefore suggest different pathophysiological backgrounds to these conditions on the tissue level. Furthermore are the greatest changes found in pre-menopausal POP , reflecting the severity of pelvic floor dysfunction in this group. All investigated hormone receptor isoforms or subtypes were expressed. The ER-beta protein was more expressed by in pre-menopausal women with SUI.
Methods: Para-urethral biopsies were collected from women with POP , SUI and compared to healthy controls matched according to menopausal status or age. The collagen concentration and extractability by pepsin digestion were analyzed in women with POP . Real-time RT -PCR revealed the gene signals and immunohistochemistry the protein expressions of collagen I, collagen III , the small leucin-rich proteoglycans (SLRP s) decorin, lumican and fibromodulin as well as the elastin associated proteins fibrillin-1 and fibulin-5 in POP and SUI. In SUI the sex steroid hormone receptor isoforms and subtypes ER-alpha, ER-beta, PR-(A+B), PR-B and AR were identified and quantified by scoring and image analysis (ER-alpha and ER-beta) completed by mRNA expressions analyze of ER-alpha, ER-beta, PR and AR by real-time RT -PCR .
Results: The collagen concentration was 30 % lower in the pelvic floor ECM of women younger than 53 years suffering from POP . There were lower mRNA expressions of all the investigated SLRP s and the elastin associated fibulin-5 in pre-menopausal women with POP . A 16-fold reduction of decorin mRNA was most prominent with a corresponding weaker protein expression of decorin. Postmenopausal women with POP exposed significantly lower mRNA expressions of fibromodulin and fibulin-5. A significant reduction of the mRNA expression of fibrillin-1 seen in women with SUI irrespective of menopausal status was confirmed by a lower immunoreactivity. All hormone receptor isoforms or subtypes were expressed in the pelvic floor ECM with ER-beta showing an increased expression in pre-menopausal women with SUI. A corresponding elevation in gene expression was not discovered.
Conclusion: Evidence for POP and SUI deriving from different alterations in the pelvic floor ECM has been found. The results therefore suggest different pathophysiological backgrounds to these conditions on the tissue level. Furthermore are the greatest changes found in pre-menopausal POP , reflecting the severity of pelvic floor dysfunction in this group. All investigated hormone receptor isoforms or subtypes were expressed. The ER-beta protein was more expressed by in pre-menopausal women with SUI.
List of papers:
I. Söderberg MW, Falconer C, Byström B, Malmström A, Ekman G (2004). "Young women with genital prolapse have a low collagen concentration." Acta Obstet Gynecol Scand 83(12): 1193-8
Pubmed
II. Söderberg MW , Byström B, Kalamajski S, Malmström A, Ekman-Ordeberg G (2008). "Down-regulations of small leucine rich repeat proteoglycans and fibulin‑5 in pelvic organ prolapse." (Submitted)
III. Söderberg MW , Byström B, Hammarström M, Malmström A, Ekman‑Ordeberg G (2008). "Decreased expression of fibrillin-1 in stress urinary incontinence." (Submitted)
IV. Söderberg MW, Johansson B, Masironi B, Byström B, Falconer C, Sahlin L, Ordeberg GE (2007). "Pelvic floor sex steroid hormone receptors, distribution and expression in pre- and postmenopausal stress urinary incontinent women." Acta Obstet Gynecol Scand 86(11): 1377-84
Pubmed
I. Söderberg MW, Falconer C, Byström B, Malmström A, Ekman G (2004). "Young women with genital prolapse have a low collagen concentration." Acta Obstet Gynecol Scand 83(12): 1193-8
Pubmed
II. Söderberg MW , Byström B, Kalamajski S, Malmström A, Ekman-Ordeberg G (2008). "Down-regulations of small leucine rich repeat proteoglycans and fibulin‑5 in pelvic organ prolapse." (Submitted)
III. Söderberg MW , Byström B, Hammarström M, Malmström A, Ekman‑Ordeberg G (2008). "Decreased expression of fibrillin-1 in stress urinary incontinence." (Submitted)
IV. Söderberg MW, Johansson B, Masironi B, Byström B, Falconer C, Sahlin L, Ordeberg GE (2007). "Pelvic floor sex steroid hormone receptors, distribution and expression in pre- and postmenopausal stress urinary incontinent women." Acta Obstet Gynecol Scand 86(11): 1377-84
Pubmed
Issue date: 2008-11-21
Rights:
Publication year: 2008
ISBN: 978-91-7409-235-6
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