Pediatric Surgery International

, Volume 22, Issue 11, pp 875–879 | Cite as

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb

  • Hiroaki Kitagawa
  • Kevin C. Pringle
  • Junki Koike
  • Hideki Nagae
  • Jane Zuccollo
  • Yuriko Sato
  • Yasuji Seki
  • Shinichirou Fujiwaki
  • Munechika Wakisaka
  • Koonosuke Nakada
Original Article

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.

Keywords

Fetal surgery Obstructive uropathy Bladder function Posterior urethral valve 

References

  1. 1.
    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 162:854–860PubMedCrossRefGoogle Scholar
  2. 2.
    Elder JS, O’grady JP, Ashmead G, Duckett JW, Philipson E (1990) Evaluation of fetal renal function: unreliability of fetal urinary electrolytes. J Urol 144:574–578PubMedGoogle Scholar
  3. 3.
    Freedman AL, Johnson MP, Smith CA, Gonzalez R, Evans MI (1999) Long term outcome in children after antenatal intervention for obstructive uropathies. Lancet 31:374–377CrossRefGoogle Scholar
  4. 4.
    Freedman AL, Johnson MP, Gonzalez R (2000) Fetal therapy for obstructive uropathy: past, present future? Pediatric Nephrol 14:167–176CrossRefGoogle Scholar
  5. 5.
    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 34:1678–1683PubMedCrossRefGoogle Scholar
  6. 6.
    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 39:1849–1852PubMedCrossRefGoogle Scholar
  7. 7.
    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 41:394–402PubMedCrossRefGoogle Scholar
  8. 8.
    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 109–148Google Scholar
  9. 9.
    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 38:1785–1789PubMedCrossRefGoogle Scholar
  10. 10.
    Holmes N, Harrison MR, Baskin LS (2001) Fetal surgery for posterior urethral valves: long term postnatal outcomes. Pediatrics 108:E7PubMedCrossRefGoogle Scholar
  11. 11.
    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 21:25–28PubMedCrossRefGoogle Scholar
  12. 12.
    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 162:832–840PubMedCrossRefGoogle Scholar
  13. 13.
    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 155:694–698PubMedCrossRefGoogle Scholar
  14. 14.
    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 148:491–496PubMedGoogle Scholar
  15. 15.
    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 165:2235–2240PubMedCrossRefGoogle Scholar
  16. 16.
    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 122:103–111PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Hiroaki Kitagawa
    • 1
  • Kevin C. Pringle
    • 2
  • Junki Koike
    • 3
  • Hideki Nagae
    • 3
  • Jane Zuccollo
    • 2
  • Yuriko Sato
    • 1
  • Yasuji Seki
    • 1
  • Shinichirou Fujiwaki
    • 4
  • Munechika Wakisaka
    • 1
  • Koonosuke Nakada
    • 1
  1. 1.Division of Pediatric SurgerySt. Marianna University School of MedicineKawasakiJapan
  2. 2.Department of Obstetrics and GynecologyWellington School of MedicineWellington SouthNew Zealand
  3. 3.Department of PathologySt. Marianna University School of MedicineKawasakiJapan
  4. 4.Department of Obstetrics and GynecologySt. Marianna University, Yokohama City Seibu HospitalYokohama, KanagawaJapan

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