RU 04. Pathology of urethral fibrous - muscular system related to parturition - induced stress urinary incontinence and TGF-β1/Smad pathway

Background: Although progress has been made in the treatment of stress urinary incontinence (SUI), our understanding of its etiology underlying the condition is poor.

Objective: We examined structural components and the role of TGF-β1/Smad pathway in the urethra by parturition-induced stress urinary incontinence. Design, setting, and participants: Forty 8-week-old Sprague-Dawley female rats at gestational day 16 were used and immediately after delivery, the rats underwent vaginal balloon dilation for 4 hours. One week later, the rats were anesthetized and both ovaries were excised.

Measurements: One month later after ovariectomy, Conscious cystometry and Leak-Point Pressure (LPP) were measured by MP150. Multiple cystometric variables were recorded by obtaining mean values of five voiding cycles. Histological examination (Masson's trichrome stain, picrosirius red stain, Hart's elastin stain, Gordon & Sweet's stain and immunohistochemical stain) and western blot were performed followed by urodynamic assays.

Results and Limitations: Four weeks after ovariectomy, SUI was noted in seventeen of 20 experimental rats. The urethras of SUI rats have more extracellular matrix (ECM) and less muscle. Total collagen fiber and reticular fiber from SUI rats are more than control rats. Meanwhile elastic fibers and reticular fibers showed fragmentized and disorganized which mean the fibrousmuscular system of SUI rats was impaired. The expression of TGF-β1 and Smad2 protein and activity of Smad2 evaluated by immunohistochemistry and western blot was higher in SUI rats than in control rats.

Conclusions: The fibrous-muscular system of urethra was impaired in SUI rats. Upregulation of TGF-β1 and Smad2 and activation of Smad2 signaling pathway in the urethra of SUI rats might play important role in parturition-induced structural changes and deterioration of urethra closing pressure.