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Development of an animal model to study congenital urinary obstruction

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Abstract

Purpose

We outline the development of a reliable model of obstructive uropathy in fetal lambs highlighting our understanding of the critical time points for interventions and the variability of any such model. We identify some discoveries that may have clinical implications.

Methods

The model requires 60-day-gestation fetal lambs. In lambs, glomerulogenesis is complete by 90 days gestation. (Term is 145 days.) The ability to develop a reliable method of creating bladder outlet obstruction in females, ligating both the urethra and urachus was critical. The lambs are bred to an accuracy of ±24 h.

Results

Creating the model at 50–60 days gestation, produces different expressions of renal dysplasia in groups of lambs undergoing identical interventions at the same stage of gestation. Early complete urethral obstruction can produce the Potter phenotype. An appropriately timed vesico-amniotic shunt preserves renal development, producing a shrunken, non-compliant bladder. Shunting the normal fetal bladder at 80 days gestation produces a similar bladder. Provision of a low-pressure valve in the shunt preserves bladder development and compliance. Using a high-pressure shunt produces results similar to non-shunted lambs.

Discussion

We developed a reliable animal model for obstructive uropathy. Being alert to peripheral results can lead to new findings.

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Acknowledgments

None of these studies would have been possible without the expertise of Doug Jensen who has been able to consistently breed ewes on the required date to provide lambs that were within 24 h of the required gestational age at the time of our interventions. Most of the sutures were provided by the Covidien Group, Japan. These studies were funded by a series of Grants-in-Aid for Scientific Research (C) from the Japanese Society for Grant in Aid for Scientific Research. Some of the studies were also partially funded by a grant from Phil & Teds, through the Wellington Surgical Research Trust. The Anesthesia study was also funded by a grant from Johnson & Johnson, through the Wellington Surgical Research Trust. The authors thank Shigeko Oonuma for assistance over the years in processing the histology.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, School of Medicine and Health Sciences, University of Otago, Wellington, P.O. Box 7343, Wellington South, 6242, Wellington, New Zealand

    K. C. Pringle & J. Zuccollo

  2. Department of Pediatric Surgery, St Marianna University School of Medicine, Kawasaki, Japan

    H. Kitagawa & Y. Seki

  3. Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan

    J. Koike

Authors
  1. K. C. Pringle
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  2. H. Kitagawa
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  3. Y. Seki
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  4. J. Koike
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  5. J. Zuccollo
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Corresponding author

Correspondence to K. C. Pringle.

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Pringle, K.C., Kitagawa, H., Seki, Y. et al. Development of an animal model to study congenital urinary obstruction. Pediatr Surg Int 29, 1083–1089 (2013). https://doi.org/10.1007/s00383-013-3408-3

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  • DOI: https://doi.org/10.1007/s00383-013-3408-3

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