Evaluation of smooth muscle and collagen subtypes in normal newborns and those with bladder exstrophy

Purpose: Many patients who undergo bladder exstrophy closure as newborns, subsequent epispadias repair and later bladder neck reconstruction become completely continent yet complications can occur. After successful initial exstrophy closure and later epispadias repair some patients may fail to gain sufficient capacity for bladder neck reconstruction or satisfactory capacity and continence after bladder neck reconstruction. In an attempt to understand the pathogenesis of these failures we compared bladder biopsies from normal neonates and those with exstrophy. Materials and Methods: Bladder biopsies obtained from the midline of the bladder wall just above the base of the trigone from 12 newborns with exstrophy were compared to bladder sections from 9 neonatal cadavers. All bladder specimens were stained with monoclonal antibodies against type I, III or IV collagen and a subset was further stained with Masson's trichrome to define the extracellular matrix. All specimens were then analyzed using a color digital image analysis system. Results: At initial examination of the extracellular matrix there was an increase in the collagen-to-smooth muscle ratio from 0.38 in controls to 1.2 in newborns with exstrophy, comprising an increase in collagen and decrease in smooth muscle. The collagen component of the extracellular matrix was then further defined to quantitate the amount of each collagen type (I, III and IV) deposited. We then evaluated the ratio of collagen type-to-total collagen sampled. Compared to control bladders there was no statistical difference in the amount of type I or IV in the bladders of newborns with exstrophy at initial closure. However, there was a 3-fold increase in type III collagen (0.14 ± 0.05 to 0.46 ± 0.2%, p <0.001) in the bladders of neonatal controls versus newborns with exstrophy. Conclusions: This alteration in collagen makeup may represent an earlier developmental stage of the exstrophy bladder at birth, which then remodels and changes after successful initial closure. Further studies are underway to examine the collagen composition of bladders at bladder neck reconstruction, failed closures and augmentation.