Myocyte Apoptosis in Primary Obstructive Megaureters: The Role of Decreased Vascular and Neural Supply

Abstract

We compared myocyte apoptosis index, microvessel density and nerve supply as well as muscular and collagen composition in the obstructed ureteral endings of children with primary obstructive megaureter and normal controls. Tissue specimens were obtained during ureteral reimplantation in 16 patients with primary obstructive megaureter. For the control group normal ureteral endings were taken at autopsy from 19 age and sex matched children. In all specimens we determined the myocyte apoptosis index, number of CD31 positive microvessels, alpha-actin positive muscular component and number of nerve terminals. The collagen fibers were also specifically stained. The myocyte apoptosis index was higher in obstructed vesicoureteral junctions (10.14%+/-1.03%) compared to controls (2.11%+/-0.21%, p<0.001). Mean number of vascular elements per microscopic field was lower in ureteral endings of patients with obstructive megaureter compared to controls (p<0.001). The number of nerve endings was also significantly lower in obstructed ureteral endings. There was a negative correlation between the number of microvessels and myocyte apoptosis index in both study groups. In obstructed megaureters the number of nerve endings was also negatively correlated with myocyte apoptosis index but positively correlated with the number of microvessels. In obstructed vesicoureteral junctions the proportion of muscular component was lower and the proportion of collagen fibers was higher compared to normal controls. Positive correlation was found between the myocyte apoptosis index and the percentage of collagenous component in both study groups. Congenital defective vascular development may result in myocyte apoptosis, and reduction of neural elements and muscular components in obstructed vesicoureteral junctions. Subsequent substitution of connective tissue may lead to functional obstruction in primary obstructive megaureter.