DIFFERENT ORGANIZATION OF COLLAGEN FIBRILS IN STRESS-INCONTINENT WOMEN OF FERTILE AGE

Objective. The objective was to test the hypothesis that stress urinar y incontinence in women is correlated to changes in the paraurethral c onnective tissue ultrastructure and metabolism. Methods. Transvaginal biopsies were obtained from the paraurethral connective tissue in wome n of fertile age with stress urinary incontinence and in matched conti nent controls. All the stress-incontinent women were characterized wit h urodynamic investigation. In the biopsies, collagen concentration, m easured as hydroxyproline, and the degree of extraction by pepsin dige stion were quantified. Proteoglycan composition and concentration were analyzed using Alcian blue precipitation, followed by electrophoretic separation and quantification. Using Northern blots mRNA levels for t he collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen organiz ation was examined with transmission electron microscopy and the diame ters of collagen fibrils were analyzed with an interactive image analy sis system (IBAS, Zeiss/Kontron). Results. The biochemical and morphol ogical analyses exposed a significant difference in the paraurethral c onnective tissue between stress urinary incontinent women before menop ause 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 lev el of mRNA for collagen I and III in the incontinent group indicates t hat the differences can be related to an altered collagen metabolism. No change of proteoglycan amount or composition was observed, resultin g in a significantly lower proteoglycan/collagen ratio in the incontin ent group of women. Conclusion. 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. T hese alterations should result in a more rigid form of extracellular m atrix, suggesting a connective tissue with impaired mechanical functio n.