A large animal model of bladder exstrophy: Observations of bladder smooth muscle and collagen content

Purpose: The development of adequate bladder capacity is not ensured in all patients with bladder exstrophy despite successful bladder closure and reconstruction. To determine the factors leading to the development and maturation of the exstrophic bladder we created a large animal model of exstrophy. We compared biopsies obtained from a cohort of experimentally induced exstrophic neonatal sheep bladders to those of normal control bladders and related the findings to a previously reported comparison of human neonatal normal and exstrophic bladders. Materials and Methods: Bladder specimens of 7 newborn lambs with experimentally induced exstrophy were compared to specimens of 10 newborn control lamb bladders. All specimens were stained with Masson's trichrome as well as with specific monoclonal antibodies to types I and III collagen. Stained sections were then analyzed using a morphometric image analysis system to quantify the amounts of smooth muscle and collagen present. Results: A significant increase in the ratio of collagen-to-smooth muscle was noted in exstrophic versus normal control bladders (p <0.05). This difference was similar to that in the previous study of neonatal human bladders. There was no significant difference in the ratios of types I and III collagen in the 2 groups of sheep bladders. This finding is different from that reported in the previous human studies. Conclusions: Overall changes in the ratio of smooth muscle-to-collagen in the sheep exstrophy model are similar to those in humans. However, the differences in collagen types I and III do not seem to be present.