Development of the human bladder and ureterovesical junction

Abstract

The urinary bladder collects urine from the kidneys and stores it until the appropriate moment for voiding. The trigone and ureterovesical junctions are key to bladder function, by allowing one-way passage of urine into the bladder without obstruction. Embryological development of these structures has been studied in multiple animal models as well as humans. In this report we review the existing literature on bladder development and cellular signalling with particular focus on bladder development in humans. The bladder and ureterovesical junction form primarily during the fourth to eighth weeks of gestation, and arise from the primitive urogenital sinus following subdivision of the cloaca. The bladder develops through mesenchymal-epithelial interactions between the endoderm of the urogenital sinus and mesodermal mesenchyme. Key signalling factors in bladder development include shh, TGF-β, Bmp4, and Fgfr2. A concentration gradient of shh is particularly important in development of bladder musculature, which is vital to bladder function. The ureterovesical junction forms from the interaction between the Wolffian duct and the bladder. The ureteric bud arises from the Wolffian duct and is incorporated into the developing bladder at the trigone. It was previously thought that the trigonal musculature developed primarily from the Wolffian duct, but it has been shown to develop primarily from bladder mesenchyme. Following emergence of the ureters from the Wolffian ducts, extensive epithelial remodelling brings the ureters to their final trigonal positions via vitamin A-induced apoptosis. Perturbation of this process is implicated in clinical obstruction or urine reflux. Congenital malformations include ureteric duplication and bladder exstrophy.

The Swedish infant high-grade reflux trial: Study presentation and vesicoureteral reflux outcome

“…The cranial end of the ureteric bud becomes the renal pelvis and the stalk of the bud becomes the ureter. The common nephric duct (the most posterior part of the mesonephric duct) then undergoes apoptosis which brings the ureters into contact with the urogenital sinus epithelium and, after extensive epithelial remodelling, to their final trigonal positions [24,25] (Figures 4 and 5).…”

Immunohistochemical expression analysis of the human fetal lower urogenital tract

“…1). The urethra begins at the bladder neck (Cunha et al, 2018b; Liaw et al, 2018), which was rarely identified in these gross pelvic specimens. The prostate (rarely seen in these gross specimens) is located below the bladder and encloses the prostatic urethra (Cunha et al, 2018b).…”

“…The bladder arises from the urogenital sinus which is endodermal in origin (Liaw et al, 2018). The urethra of the human male and female extends caudally through the pelvis and is continuous with the urethral (and vestibular) plate within the developing genital tubercle.…”

A comparison of prostatic development in xenografts of human fetal prostate and human female fetal proximal urethra grown in dihydrotestosterone-treated hosts

“…The Q3 prostate of all species develops from the urogenital sinus (UGS), a derivative of the ventral division of the cloaca (Liaw et al, 2018;Yamada et al, 2003). Solid prostatic buds emerge from human urogenital sinus epithelium (UGE) immediately below the developing bladder at about 10 weeks of gestation (Cunha et al, 2018).…”