Embryogenesis of Ureteral Anomalies: A Unifying Theory

Abstract

Extensive gross, microscopic and clinical studies of various ureteral anomalies have enabled investigators to set forth theories regarding the aetiologies of these anomalies consistent with observed fact. Synthesis of these observations allows for a simplified classification of mega‐ureter (primary obstructed. reflux and non‐obstructed, non‐reflux mega‐ureters), ureterocele, duplex ureters and ectopic ureters based upon some combination of mesenchymal differentiation anomalies and location anomalies. A defect early in mesenchymal differentiation would be expected to result in panureteral disease. A defect later in development would result in a focal abnormality anywhere along the course of the ureter. Influence upon ureteral bud mesenchyme by local expansion factors in the bladder base may result in various types of ureterocele. Position of the ureteral orifice on the trigone or in Wolffian duct derivatives would occur in accordance with the Weigert‐Meyer principle and would correlate with upper tract dysplasias. Thus, an attempt has been made to systematize and trace the origins of mega‐ureter, ureterocele, duplex ureters and ectopic ureters to defects of differentiation of the basic mesoblastic cell in aberrant locations of the ureteral bud.

The development of the bladder trigone, the center of the anti-reflux mechanism

“…Analysis of human and animal specimens has led to the suggestion that the trigone is structurally distinct from the bladder and urethra, differentiating from the common nephric duct and ureter (Hutch, 1972;Tanagho, 1981;Weiss, 1988;Wesson, 1925). Other studies suggest that the bladder muscle (detrusor) might also be part of the trigone structure (Meyer, 1946).…”

Hypoplastic thymus and T-cell reduction in EECUT syndrome

“…The persistence of this membrane may be an intrinsic epithelial defect which causes a so-called stenotic ureterocele. Others have suggested a mesenchymal defect as the primary defect in ureteroceles [Weiss, 1988] because abnormal differentiation of muscle fibers had been observed with various techniques [Tanagho et al, 1965;Tokunaka et al, 1981]. Again, others have stressed pathologic innervation as the prime pathogenetic factor [Friedrich et al, 1987].…”

Familial ureteral abnormalities syndrome: genomic mapping, clinical findings

“…Weiss [4] proposed that development of all primary ureteral abnormalities may be accounted for by a basic defect in the interaction between the surrounding mesoblastic cells and the transitional epithelium which lines the bladder, ureter, and collecting ducts. Inappropriate inductive interactions resulting in an increased ratio of fibroblasts to myoblasts might alter the compliance of the ureter, resulting in partial to essentially complete obstructions and reflux.…”

“…Several investigators have suggested a common embryological origin for upper and lower ureteral abnormalities (UPJO, VUR and duplicated systems). Atwell et al [3] and Weiss [4] have proposed a mechanism involving inductive interactions between the transitional epithelium which lines the bladder, ureter, and collecting ducts and the surrounding mesoblastic cells which develop into either myoblasts or fibroblasts. If all abnormalities manifested in a pedigree have such a common embryological origin, the particular urinary tract abnormality which presents in each affected individual may depend on the specific time in development during which the mutation was expressed.…”