Abstract
Vesico-amniotic shunting of obstructive uropathy in fetal lambs produced a thick-walled, poorly compliant bladder. We report the early histological changes in the obstructed bladder wall. We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. Vesicostomy or vesico-amniotic shunt tube insertion and biopsy of the bladder wall were performed 21 days later. The fetuses were delivered at term (145 days) and the kidneys and bladder sampled for histology. Colloidal iron (Col Fe), and alpha-smooth muscle actin (α-SMA) immunohistochemical stains were used for these samples. Seventeen fetuses were shunted with 15 biopsies taken at that time. Six (shunt failure or missed urachal ligation) were excluded. All biopsies taken at shunting had positive Col Fe and α-SMA. Term lambs had mild multicystic dysplastic kidney (MCDK) in five, severe MCDK in two, and hydronephrosis in four. All bladders had small volume and were severely fibrotic. Fetal shunt operations 3 weeks after the creation of obstructive uropathy provided partial preservation of renal histology but did not preserve normal bladder histology. We suggest that the high hyaluronic acid synthesis activity or hyperplasia of the myofibroblasts in the dilated fetal bladder wall at the time of shunting results in irreversible damage to the developing bladder muscle and fibrosis.
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References
Gobet R, Bleakley J, Cisek L, Kaefer M, Moses MA, Femandez CA, Peters CA (1999) Fetal partial urethral obstruction causes renal fibrosis and is associated with proteolytic imbalance. J Urol 162:854–860
Elder JS, O’grady JP, Ashmead G, Duckett JW, Philipson E (1990) Evaluation of fetal renal function: unreliability of fetal urinary electrolytes. J Urol 144:574–578
Freedman AL, Johnson MP, Smith CA, Gonzalez R, Evans MI (1999) Long term outcome in children after antenatal intervention for obstructive uropathies. Lancet 31:374–377
Freedman AL, Johnson MP, Gonzalez R (2000) Fetal therapy for obstructive uropathy: past, present future? Pediatric Nephrol 14:167–176
Kitagawa H, Pringle KC, Zuccollo J, Stone P, Nakada K, Kawaguchi F, Nakada M, Wakisaka M, Furuta S, Koike J, Seki Y (1999) The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb. J Pediatr Surg 34:1678–1683
Sato Y, Kitagawa H, Pringle KC, Koike J, Zuccollo J, Robinson R, Wakisaka M, Seki Y, Nakada K (2004) Effect of early vesicostomy in obstructive uropathy on bladder development. J Pediatr Surg 39:1849–1852
Kitagawa H, Pringle KC, Koike J, Zuccolo J, Seki Y, Wakisaka M, Sato Y, Sato H, Nagae H, Nakada K (2006) Vesicoamniotic shunt for complete urinary tract obstruction is partially effective. J Pediatr Surg 41:394–402
Pringle KC (1984) Fetal lamb and fetal lung growth following creation and repair of a diaphragmatic hernia. In: Nathanielsz PW (ed) Animal models in fetal medicine, vol IV. Perinatology Press, Ithaca, pp 109–148
Kitagawa H, Pringle KC, Koike J, Zuccollo J, Seki Y, Fujiwaki S, Sato H, Nagae H Nakada K (2003) Optimal timing of prenatal treatment of obstructive uropathy the fetal lamb. J Pediatr Surg 38:1785–1789
Holmes N, Harrison MR, Baskin LS (2001) Fetal surgery for posterior urethral valves: long term postnatal outcomes. Pediatrics 108:E7
Kitagawa H, Pringle KC, Koike J, Zuccollo J, Sato Y, Sato H, Aoba T, Wakisaka M, Nakada K (2005) Fetal hydrops in experimental obstructive uropathy resolves after vesicostomy formation: is this cause and effect? Pediatr Surg Int 21:25–28
Bagli DJ, Joyner BD, Mahoney SR, McClulloch L (1999) The healuronic acid receptor is induced by stretch injury of rat bladder in vivo and influences smooth muscle cell contraction in vitro. J Urol 162:832–840
Holmdahl G, Sillen U, Hanson E, Hermansson G, Hjalmas K (1996) Bladder dysfunction in boys with posterior urethral valves before and after puberty. J Urol 155:694–698
Peters CA, Vasavada S, Dator D, Carr M, Shapiro E, Lepor H, McConnell J, Retik AB, Mandell J (1992) The effect of obstruction on the developing bladder. J Urol 148:491–496
Capolicchio G, Aitken KJ, Gu JX, Reddy P, Bagli DJ (2001) Extracellular matrix gene responses in a novel ex vivo model of bladder stretch injury. J Urol 165:2235–2240
Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-β1 induces α-SMA expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111
Acknowledgments
This study was supported by the Japanese Society for Grant in aid of Scientific Research (C). Suture materials were supplied by Tyco Healthcare Tokyo, Japan. All animals are consistently bred to timing of <24 h by Doug Jensen of the Wallaceville Animal Research Facility. The authors thank Shigeko Ohnuma for assistance in processing the histology.
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Kitagawa, H., Pringle, K.C., Koike, J. et al. Early bladder wall changes after creation of obstructive uropathy in the fetal lamb. Pediatr Surg Int 22, 875–879 (2006). https://doi.org/10.1007/s00383-006-1755-z
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DOI: https://doi.org/10.1007/s00383-006-1755-z