BACKGROUND: Normal bladder cycling during childhood may impact long-term urological health. Disruptions to normal bladder cycling, due to conditions such as bladder exstrophy, anuria/renal failure, stress urinary incontinence, or cutaneous vesicostomy (CV), may alter bladder behavior once normal function resumes. CV is the most common form of urinary diversion for incontinence in neonates and young children. Although primarily intended as a temporary measure to divert urine for external collection, numerous studies indicate that many patients continue to maintain their CV into adulthood.
METHODS: With IACUC approval, 8-week-old CD-1 mice were divided into control and CV groups. The CV procedure involved creating a 3-4 mm stoma, connecting the bladder to the skin surface, while controls underwent sham surgery. Ten days post-operation, the effects of CV were evaluated by in vitro physiological recording using bladder strips for detrusor muscle (DSM) contractility, bladder histology by Masson’s trichrome staining, and gene expression analysis by qPCR.
RESULTS: CV mice showed increased bladder weight (30.4 mg vs. 19.6 mg, p=0.03), a 62.8% decrease in DSM contractility (KCl), and a 29.5% decrease in nerve-mediated contraction compared to the control group (Figure 1A, 1B). Carbachol dose-response curves indicated altered cholinergic receptor sensitivity (EC50: 5.55 μM for CV vs. 3.28 μM for controls) (Figure 2). CV mice showed a rise in nerve-mediated contractility with Substance-P incubation compared to control (218.5% vs. 165.5%, p=0.01). Histological assessments of the bladder sections showed an increase in bladder thickness, lamina propria, and a decrease in DSM layer along with an increase in collagen deposition in the CV group (Figure 1C).
CONCLUSIONS: Bladder cycle disruption induced by CV in mice yielded decreased DSM contractility in response to direct activation of myocytes and bladder nerve stimulation, with signs of bladder fibrosis. These findings suggest that bladder cycling disruption may cause significant functional and structural alterations in the bladder.
