Prenatal and postnatal neuromuscular development of the ureterovesical junction

Purpose: The mechanisms underlying functional maturation of the ureterovesical junction during infancy are still not fully understood. We analyzed the development of smooth muscle components of the ureterovesical junction and their nerve supply in the fetal, newborn and adolescent pig. Materials and Methods: Bladder specimens were obtained from porcine fetuses at gestational ages 60 days (5) and 90 days (5), newborn piglets (5) and 6-month-old pigs (4). Serial sections of the ureterovesical junction were investigated by Masson's trichrome, and hematoxylin and eosin histological staining, enzyme immunohistochemistry for a-smooth muscle actin and desmin, as well as double immunofluorescence staining using the neuronal marker peripherin and smooth muscle actin. Results: At day 60 the detrusor muscle already consisted of distinctive muscle bundles with rich innervation, while the smooth muscle coat of the extravesical ureter and subsequently the intravesical ureter had only started to differentiate. At day 60 innervation of the extravesical ureteral smooth muscle was well developed, while the innervation of the intramural part did not mature until birth. Muscle fibers of the periureteral sheath were well distinguishable at day 60 but innervation of these fibers was sparse during fetal life and showed a remarkable increase during the postnatal period. All smooth muscle components showed a striking increase in muscle bulk between the neonatal and adolescent stages. Conclusions: Our findings show that the smooth muscle components and innervation of the ureterovesical junction continue to mature during the postnatal period. This may have implications for managing ureterovesical junction disorders.