Different organization of collagen fibrils in stress-incontinent women of fertile age
The objective was to test the hypothesis that stress urinary incontinence in women is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.
Transvaginal biopsies were obtained from the paraurethral connective tissue in women of fertile age with stress urinary incontinence and in matched continent controls. All the stress-incontinent women were characterized with urodynamic investigation. In the biopsies, collagen concentration, measured as hydroxyproline, and the degree of extraction by pepsin digestion were quantified. Proteoglycan composition and concentration were analyzed using Alcian blue precipitation, followed by electrophoretic separation and quantification. Using Northern blots mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen organization was examined with transmission electron microscopy and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).
The biochemical and morphological analyses exposed a significant difference in the paraurethral connective tissue between stress urinary incontinent women before menopause and comparable controls. The collagen concentration was almost 30% higher and the diameters of the collagen fibrils were 30% larger in the incontinent group of women. Also the organization of the collagen fibrils differed, with considerably higher cross-linking. A higher level of mRNA for collagen I and III in the incontinent group indicates that the differences can be related to an altered collagen metabolism. No change of proteoglycan amount or composition was observed, resulting in a significantly lower proteoglycan/collagen ratio in the incontinent group of women.
Stress urinary incontinence in fertile women is associated with a change in collagen metabolism resulting in an increased concentration of collagen and larger collagen fibrils. These alterations should result in a more rigid form of extracellular matrix, suggesting a connective tissue with impaired mechanical function.
Available from: PubMed Central
- "Therefore, the changes in collagen has been suggested an important etiology of POP,7 and the use of graft in pelvic reconstructive surgery is growing.9 However, several studies have reported conflicting results showing that collagen in POP patients was either decreased, increased or unaltered.10-12 These results, nevertheless, suggest the possibility of the development of POP by the alteration of the tension of connective tissue caused by the changes in the components of collagen. "
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ABSTRACT: To evaluate the possible influence of G-->T substitution at the Sp1-binding site of the COLIA1 gene on the risk of pelvic organ prolapse (POP).
The study group consisted of 15 women with advanced stage POP. Fifteen control subjects with uterine myomas among the postmenopausal women were matched for age and parity. DNA was obtained from peripheral blood leukocytes. The fragments of the first intron of the COLIA1 gene were amplified by real time polymerase chain reaction. The polymorphism was identified using LightCycler Technology with hybridization probes. Sequencing reactions were performed on each template using commercial primer.
Two groups had no significant difference in medical history, surgical, and smoking history. The homozygous peaks in two groups were noted at 57 on melting curve analysis. Sequencing reactions confirmed the G/G alleles in the 30 specimens tested. We could not find any polymorphism at the Sp1-binding site in COLIA1 gene with advanced stage POP. Statistical significance was considered to be p < .05.
The polymorphism of the Sp1-binding site in the COLIA1 gene did not contribute to the development of POP in Korea.
Available from: Yan Wen
- "Elastin stained green and these same fibers also stained red indicating co-expression of BGN, DCN and FMOD with elastin. Falconer et al. (1998) reported no change in PG amount or composition in paraurethral connective tissue in premenopausal women with SUI. However, these patients were not separated into proliferative and secretory phases. "
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ABSTRACT: To investigate changes in mRNA and protein levels of biglycan (BGN), decorin (DCN) and fibromodulin (FMOD) in vaginal wall tissue from women with stress urinary incontinence (SUI) compared to menstrual-cycle matched continent women.
We determined mRNA expressions of BGN, DCN and FMOD by quantitative real-time PCR. They were localized in vaginal wall tissue by immunohistochemistry. We performed western blot analysis to examine protein expression.
BGN, DCN and FMOD co-localized with collagen and elastin in the extracellular matrix (ECM) of vaginal wall tissue from both groups. The mRNA expression of FMOD was significantly lower in cases versus controls in the proliferative phase (P = 0.03). DCN mRNA expression in cases was higher in the proliferative (P = 0.05) and secretory phases (P = 0.02) versus controls. BGN mRNA expression showed no significant differences in either phase. Protein expression of FMOD in cases was lower in the proliferative phase versus controls (six out of nine pairs), whereas DCN and BGN protein expression in the secretory phase in cases was higher (seven out of nine pairs).
BGN, DCN and FMOD expressions in vaginal wall tissue differ in women with SUI and are hormonally modulated. Differences in small proteoglycans may contribute to the altered pelvic floor connective tissues found in these women.
Available from: Hans Peter Dietz
- "Previous studies have found elbow hyperextension to be associated with an increased risk of postnatal urinary incontinence (Tincello et al., 2002) and a general measure of joint hypermobility to be associated with a higher prevalence of genital prolapse (Norton et al., 1995). These associations may reflect aspects of collagen metabolism, as metabolic changes have been associated with both prolapse (Jackson et al., 1996) and incontinence (Falconer et al., 1998). Furthermore, connective tissue strength may contribute to variability in measures of both joint and pelvic organ mobility, and genetic factors influencing connective tissue strength may be a source of covariation between these measures. "
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ABSTRACT: A range of environmental risk factors, with childbirth the most notable, have been associated with the development of pelvic organ prolapse and urinary incontinence. However, indications of genetic influence (positive family histories, ethnic differences) have prompted research into the heritability of measures of pelvic organ descent and joint mobility, which have also been associated with prolapse and incontinence. Genes appear to influence about half of the variation in these measures and, furthermore, the pelvic organ measures are associated with elbow hyperextension at a phenotypic level (r approximately .2). We examined these measures in young, nulligravid women to determine if their association is due to a common genetic source. Data were collected from 178 Caucasian female co-twins and non-twin sisters, 50 of whom returned to be retested, which allowed reliability to be estimated and unreliable variance to be isolated in the multivariate analyses. Structural equation modeling was used to estimate genetic associations between latent elbow and bladder mobility factors for which heritabilities were estimated to be 0.80 and 0.64 respectively. The association between these factors appeared to be mediated by common genes (genetic r = .48, non-shared environmental r = -.06), with genes influencing latent elbow mobility accounting for 14% of the variation in latent bladder mobility. We speculate that genes influencing connective tissue structure may underlie this association.
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