Abstract
Background
Creating obstructive uropathy (OU) during glomerulogenesis in the fetal lamb results in multicystic dysplastic kidney (MCDK) at term. We explored this using immunohistochemical techniques.
Method
OU was created in fetal lambs at 60-day gestation, ligating the urethra and urachus. The kidneys of MCDK lambs, 60-day gestation fetal lambs, full-term lamb (145 days), term sham-operated lambs, and adult ewes were evaluated by HE staining, and immunohistochemistry with paired box genes 2 (PAX2) and CD10.
Results
Multiple cysts were found in the MCDK model. CD10 was expressed in proximal tubular epithelial cells, glomerular epithelial cells, and medullary stromal cells in the kidneys of 60-day gestation fetal lambs and full-term lambs and adult ewes. PAX2 expression was found in ureteric buds, C- and S-shaped bodies, epithelial cells of collecting ducts, and Bowman's capsule of fetal kidneys at 60-day gestation, but only in the collecting ducts of full-term fetal lambs and adult ewes. Both CD10 and PAX2 were expressed in the cystic epithelial cells of the MCDK model.
Discussion
PAX2 expression in cystic epithelial cells suggests that cyst formation is associated with disturbed down-regulation of PAX2 in the nephrogenic zone epithelial cells during the renal development in the OU model.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hains DS, Bates CM, Ingraham S, Schwaderer AL (2009) Management and etiology of the unilateral multicystic dysplastic kidney: a review. Pediatr Nephrol 24(2):233–241
Kitagawa H, Pringle KC, Koike J, Zuccollo J, Nakada K (2001) Different phenotypes of dysplastic kidney in obstructive uropathy in fetal lambs. J Pediatr Surg 36(11):1698–1703
Kitagawa H, Pringle KC, Koike J, Zuccollo J, Seki Y, Fujiwaki S et al (2003) Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb. J Pediatr Surg 38(12):1785–1789
Kitagawa H, Pringle KC, Zuccolo J, Stone P, Nakada K, Kawaguchi F et al (1999) The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb. J Pediatr Surg 34(11):1678–1683
Van der Hauwaert C, Savary G, Gnemmi V, Glowacki F, Pottier N, Bouillez A et al (2013) Isolation and characterization of a primary proximal tubular epithelial cell model from human kidney by CD10/CD13 double labeling. PLoS ONE 8(6):e66750
Aoba T, Koike J, Nagae H, Kitagawa H, Pringle KC (2008) Expression of CD10 in Developmental Kidney in Fetal Lambs. J Dev Kidney 16(1):36–38
Narlis M, Grote D, Gaitan Y, Boualia SK, Bouchard M (2007) PAX2 and PAX8 regulate branching morphogenesis and nephron differentiation in the developing kidney. J Am Soc Nephrol 18(4):1121–1129
Tanaka K, Manabe S, Ooyama K, Seki Y, Nagae H, Takagi M et al (2014) Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney? J Pediatr Surg 49(12):1831–1834
Kawaguchi K, Obayashi J, Kawaguchi T, Koike J, Seki Y, Tanaka K et al (2018) The role of the ureteric bud in the development of the ovine fetal kidney. J Pediatr Surg 53(12):2502–2506
Nishiya Y, Kawaguchi K, Kudo K, Kawaguchi T, Obayashi J, Tanaka K et al (2021) The Expression of Transcription Factors in Fetal Lamb Kidney. J Dev Biol 9(2):22
Morizane R, Miyoshi T, Bonventre JV (2017) Concise Review: Kidney Generation with Human Pluripotent Stem Cells. Stem Cells 35(11):2209–2217
Torban E, Eccles MR, Favor J, Goodyer PR (2000) PAX2 suppresses apoptosis in renal collecting duct cells. Am J Pathol 157(3):833–842
Renkema KY, Winyard PJ, Skovorodkin IN, Levtchenko E, Hindryckx A, Jeanpierre C et al (2011) Novel perspectives for investigating congenital anomalies of the kidney and urinary tract (CAKUT). Nephrol Dial Transplant 26(12):3843–3851
Sanyanusin P, McNoe LA, Sullivan MJ, Weaver RG, Eccles MR (1995) Mutation of PAX2 in two siblings with renal-coloboma syndrome. Hum Mol Genet 4(11):2183–2184
Faa G, Gerosa C, Fanni D, Nemolato S, Marinelli V, Locci A et al (2012) CD10 in the developing human kidney: immunoreactivity and possible role in renal embryogenesis. J Matern Fetal Neonatal Med 25(7):904–911
O’Brien LL, McMahon AP (2014) Induction and patterning of the metanephric nephron. Semin Cell Dev Biol 36:31–38
Dressler GR, Wilkinson JE, Rothenpieler UW, Patterson LT, Williams-Simons L, Westphal H (1993) Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature 362(6415):65–67
Ostrom L, Tang MJ, Gruss P, Dressler GR (2000) Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Dev Biol 219(2):250–258
Acknowledgements
Management of the animals in the laboratory was supervised by Dr Rebecca Dyson and Taylor Wilson, animal technicians at the BRU at University of Otago, Wellington. The authors would like to thank Manabu Kubota and the other staff at the Department of Pathology, St. Marianna University School of Medicine for their assistance in processing the histology.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interests
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Nishiya, Y., Kawaguchi, K., Kudo, K. et al. Factors influencing the development of Multicystic Dysplastic Kidney (MCDK) following urinary tract obstruction in the fetal lamb. Pediatr Surg Int 38, 913–918 (2022). https://doi.org/10.1007/s00383-022-05116-z
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00383-022-05116-z