Experimental short-term fetal bladder outflow obstruction: I. Morphology and cell biology associated with urinary flow impairment

Farrugia, M.-K.; Long, D.A.; Godley, M.L.; Peebles, D.M.; Fry, C.H.; Cuckow, P.M.; Woolf, A.S.

doi:10.1016/j.jpurol.2006.01.019

« Previous Next »Journal of Pediatric Urology
Volume 2, Issue 4 , Pages 243-253, August 2006

Experimental short-term fetal bladder outflow obstruction: I. Morphology and cell biology associated with urinary flow impairment

M.-K. Farrugia
- Nephro-Urology Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford Street, London WC1N 1EH, UK
- Corresponding author. Tel.: +44 20 7905 2651; fax: +44 20 7905 2133.
D.A. Long
- Nephro-Urology Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford Street, London WC1N 1EH, UK
M.L. Godley
- Nephro-Urology Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford Street, London WC1N 1EH, UK
D.M. Peebles
- Department of Obstetrics and Gynaecology, University College London, London, UK
C.H. Fry
- Institute of Urology and Nephrology, University College London, London, UK
P.M. Cuckow
- Nephro-Urology Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford Street, London WC1N 1EH, UK
A.S. Woolf
- Nephro-Urology Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford Street, London WC1N 1EH, UK

Received 14 October 2005; accepted 9 January 2006.

Abstract

Purpose

In fetal sheep, combined urethral and urachal obstruction initiated at 75 days' gestation and maintained for 30 days led to dysmorphic bladders, similar to those found in humans with prune belly syndrome, and uniformly disrupted kidney development. We aimed to create a less severe model of fetal bladder outlet obstruction, more closely resembling infants with posterior urethral valves, and additionally to further our understanding on the role of the urachus. We hypothesized that milder morphological renal tract changes would occur after shorter term experimental obstruction.

Materials and methods

Male fetal lambs were assigned to urachal and urethral ligation, urachal ligation only or sham operations. Analyses were performed after 9 days.

Results

Concurrent urachal and urethral obstruction resulted in increased bladder weight, and protein and DNA content. Detrusor smooth muscle was well maintained, as assessed by light and electron microscopy, although urothelia showed basal apoptosis. Bladder obstruction led to hydronephrosis but failed to produce significant perturbations in urine osmolality. The nephrogenic cortex was either well preserved or was replaced by glomerular cysts; the latter group tended to have heavier bladders. Urachal obstruction alone produced similar changes suggesting that the male sheep fetal urethra is a high-resistance conduit in mid-gestation.

Conclusions

Concurrent urachal and urethral obstruction, or urachal obstruction alone, initiated in mid-gestation and maintained for 9 days leads to bladder overgrowth but preserved renal tubular function. In future, it will be interesting to determine whether bladder decompression around this stage leads to reversal of bladder overgrowth and/or ameliorates severe renal tract damage described after longer term fetal bladder outflow obstruction.

Keywords: Apoptosis, Bladder, Obstruction, Detrusor, Smooth muscle, Fetus, Kidney, Urothelium