Premature urachal closure induces hydroureteronephrosis in male fetuses

Purpose: Congenital hydronephrosis is more common in male individuals. We investigate whether an alteration in fetal bladder function induced by premature urachal closure contributes to fetal hydronephrosis, consequently explaining this male predominance. Materials and Methods: The urachus was clipped in 8 male and 4 female ovine fetuses at 95 days of gestation (term 140 days). Subjects were sacrificed, and the urinary tract was assessed at 109 and 116 days of gestation in 3 and 1 male fetuses, respectively, and at term in 4 male and 4 female lambs. Results: At 109 and 116 days of gestation 3 of the 4 male fetuses had upper tract dilatation. At term no female but 4 male lambs had hydroureteronephrosis, including some with marked pelvic dilatation and parenchymal thinning. At term mean bladder weight in the male animals with urachal clipping was 5.28 gm. (range 3.5 to 8.2), which was significantly greater than normal (p = 0.02). Bladder weight at term in the female lambs with urachal clipping was not different from normal values. Histological evaluation of the kidneys in the male lambs revealed cortical thinning and loss of medullary tissue, while the overall renal architecture was well preserved. Conclusions: Our observations indicate that normal ovine fetal urinary tract function and drainage depend on urachal function and the timing of urachal closure. Therefore, fetal hydronephrosis is associated with this alteration in bladder function but it may also be associated with other factors, such as bladder sphincter maturation or prostate development. Our experiment shows that hydroureteronephrosis develops in ovine fetuses when all bladder drainage occurs via the urethra. This condition may be an amplification of the differences in bladder outlet resistance in human fetuses, which may explain the male predominance in the various forms of hydroureteronephrosis.