Segmental up-regulation of transforming growth factor-beta in the pathogenesis of primary megaureter. An immunocytochemical study

OBJECTIVE: To examine the maturational-delay hypothesis of primary megaureter (PM), i.e. that the condition arises by a segmental maturational delay of the ureteric wall that can resolve spontaneously within the first year of life, using comparative immunocytochemistry of ureters resected from infants and from homologous pre-natal ureters. MATERIALS AND METHODS: Seventeen distal urinary tracts were obtained from children with PM who were referred for surgery (aged 6 months to 8 years, mean 2.1 years). These were compared with ureteric buds obtained from 11-week-old human and 11- to 38-week-old calf fetuses. The samples were immunostained using a monoclonal antibody specific for transforming growth factor beta (TGF-beta). RESULTS: The histological appearances of the narrowed ureteric segments from patients under 18 months old were like the fetal ureteric buds at 26-38 weeks of gestation. Positive TGF-beta immunoreactions were detected in the longitudinal muscle layer in the ureter from patients 6-12 months old. Such reactions weakened progressively in those patients older than 1 year, becoming negative in all children older than 3 years. The TGF-beta immunolabelling in resected ureters was closely similar to that in fetal ureters from 20 to 26-week old calves. CONCLUSIONS: From these results, PM should be ascribed to a segmental developmental delay of the terminal ureter arising at about 20 weeks of gestation, with a possible pathogenetic involvement of autocrine TGF-beta overexpression.