Timing of morphologic and apoptotic changes in the sheep fetal kidney in response to bladder outflow obstruction

Naeem Samnakay, Jillian Orford, Andrew Barker, Adrian Charles, Philippa Terry, John Newnham, Timothy Moss

Research output: Contribution to journalArticleResearchpeer-review

Abstract

PURPOSE: Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thirty per cent of boys with valves develop end-stage renal disease, despite intervention in the postnatal period. The timing and mechanisms of renal damage in bladder outflow obstruction are unknown. We investigated the timing of changes in morphology and apoptosis in the fetal sheep kidney in response to obstruction. MATERIALS AND METHODS: Thirty-three fetal lambs at day 70 of gestation underwent surgical creation of bladder outflow obstruction. Twenty-nine fetal lambs had sham surgery. Fetal kidneys were collected 2, 5, 10, 20 and 30 days after surgery. Renal histology was examined. Real-time PCR was used to quantify the renal cortical expression of the pro-apoptotic gene Bax and anti-apoptotic gene Bcl-X. The TUNEL technique was used to assess regional renal apoptosis in response to obstruction. RESULTS: Changes in renal morphology were evident as early as 2 days after surgery in fetuses with bladder outflow obstruction, and progressed over 20-30 days to cystic renal dysplasia. Bladder outflow obstruction increased the renal cortical expression of Bax relative to Bcl-X. Tubular apoptosis peaked after 2 days of obstruction. Blastemal apoptosis peaked after 5 days of obstruction. CONCLUSIONS: Changes in pro- and anti-apoptotic gene expression in the fetal renal cortex, and alterations in the number of apoptotic cells and renal morphology are evident soon after the onset of bladder outflow obstruction. These findings suggest that damage to the developing fetal kidney begins to occur at the onset of obstruction. Attempts to preserve renal function by antenatal interventions may best be achieved by early treatment
Original languageEnglish
Pages (from-to)216 - 224
Number of pages9
JournalJournal of Pediatric Urology
Volume2
Issue number4
DOIs
Publication statusPublished - 2006
Externally publishedYes

Cite this

Samnakay, Naeem ; Orford, Jillian ; Barker, Andrew ; Charles, Adrian ; Terry, Philippa ; Newnham, John ; Moss, Timothy. / Timing of morphologic and apoptotic changes in the sheep fetal kidney in response to bladder outflow obstruction. In: Journal of Pediatric Urology. 2006 ; Vol. 2, No. 4. pp. 216 - 224.
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title = "Timing of morphologic and apoptotic changes in the sheep fetal kidney in response to bladder outflow obstruction",
abstract = "PURPOSE: Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thirty per cent of boys with valves develop end-stage renal disease, despite intervention in the postnatal period. The timing and mechanisms of renal damage in bladder outflow obstruction are unknown. We investigated the timing of changes in morphology and apoptosis in the fetal sheep kidney in response to obstruction. MATERIALS AND METHODS: Thirty-three fetal lambs at day 70 of gestation underwent surgical creation of bladder outflow obstruction. Twenty-nine fetal lambs had sham surgery. Fetal kidneys were collected 2, 5, 10, 20 and 30 days after surgery. Renal histology was examined. Real-time PCR was used to quantify the renal cortical expression of the pro-apoptotic gene Bax and anti-apoptotic gene Bcl-X. The TUNEL technique was used to assess regional renal apoptosis in response to obstruction. RESULTS: Changes in renal morphology were evident as early as 2 days after surgery in fetuses with bladder outflow obstruction, and progressed over 20-30 days to cystic renal dysplasia. Bladder outflow obstruction increased the renal cortical expression of Bax relative to Bcl-X. Tubular apoptosis peaked after 2 days of obstruction. Blastemal apoptosis peaked after 5 days of obstruction. CONCLUSIONS: Changes in pro- and anti-apoptotic gene expression in the fetal renal cortex, and alterations in the number of apoptotic cells and renal morphology are evident soon after the onset of bladder outflow obstruction. These findings suggest that damage to the developing fetal kidney begins to occur at the onset of obstruction. Attempts to preserve renal function by antenatal interventions may best be achieved by early treatment",
author = "Naeem Samnakay and Jillian Orford and Andrew Barker and Adrian Charles and Philippa Terry and John Newnham and Timothy Moss",
year = "2006",
doi = "10.1016/j.jpurol.2006.05.007",
language = "English",
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Timing of morphologic and apoptotic changes in the sheep fetal kidney in response to bladder outflow obstruction. / Samnakay, Naeem; Orford, Jillian; Barker, Andrew; Charles, Adrian; Terry, Philippa; Newnham, John; Moss, Timothy.

In: Journal of Pediatric Urology, Vol. 2, No. 4, 2006, p. 216 - 224.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Timing of morphologic and apoptotic changes in the sheep fetal kidney in response to bladder outflow obstruction

AU - Samnakay, Naeem

AU - Orford, Jillian

AU - Barker, Andrew

AU - Charles, Adrian

AU - Terry, Philippa

AU - Newnham, John

AU - Moss, Timothy

PY - 2006

Y1 - 2006

N2 - PURPOSE: Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thirty per cent of boys with valves develop end-stage renal disease, despite intervention in the postnatal period. The timing and mechanisms of renal damage in bladder outflow obstruction are unknown. We investigated the timing of changes in morphology and apoptosis in the fetal sheep kidney in response to obstruction. MATERIALS AND METHODS: Thirty-three fetal lambs at day 70 of gestation underwent surgical creation of bladder outflow obstruction. Twenty-nine fetal lambs had sham surgery. Fetal kidneys were collected 2, 5, 10, 20 and 30 days after surgery. Renal histology was examined. Real-time PCR was used to quantify the renal cortical expression of the pro-apoptotic gene Bax and anti-apoptotic gene Bcl-X. The TUNEL technique was used to assess regional renal apoptosis in response to obstruction. RESULTS: Changes in renal morphology were evident as early as 2 days after surgery in fetuses with bladder outflow obstruction, and progressed over 20-30 days to cystic renal dysplasia. Bladder outflow obstruction increased the renal cortical expression of Bax relative to Bcl-X. Tubular apoptosis peaked after 2 days of obstruction. Blastemal apoptosis peaked after 5 days of obstruction. CONCLUSIONS: Changes in pro- and anti-apoptotic gene expression in the fetal renal cortex, and alterations in the number of apoptotic cells and renal morphology are evident soon after the onset of bladder outflow obstruction. These findings suggest that damage to the developing fetal kidney begins to occur at the onset of obstruction. Attempts to preserve renal function by antenatal interventions may best be achieved by early treatment

AB - PURPOSE: Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thirty per cent of boys with valves develop end-stage renal disease, despite intervention in the postnatal period. The timing and mechanisms of renal damage in bladder outflow obstruction are unknown. We investigated the timing of changes in morphology and apoptosis in the fetal sheep kidney in response to obstruction. MATERIALS AND METHODS: Thirty-three fetal lambs at day 70 of gestation underwent surgical creation of bladder outflow obstruction. Twenty-nine fetal lambs had sham surgery. Fetal kidneys were collected 2, 5, 10, 20 and 30 days after surgery. Renal histology was examined. Real-time PCR was used to quantify the renal cortical expression of the pro-apoptotic gene Bax and anti-apoptotic gene Bcl-X. The TUNEL technique was used to assess regional renal apoptosis in response to obstruction. RESULTS: Changes in renal morphology were evident as early as 2 days after surgery in fetuses with bladder outflow obstruction, and progressed over 20-30 days to cystic renal dysplasia. Bladder outflow obstruction increased the renal cortical expression of Bax relative to Bcl-X. Tubular apoptosis peaked after 2 days of obstruction. Blastemal apoptosis peaked after 5 days of obstruction. CONCLUSIONS: Changes in pro- and anti-apoptotic gene expression in the fetal renal cortex, and alterations in the number of apoptotic cells and renal morphology are evident soon after the onset of bladder outflow obstruction. These findings suggest that damage to the developing fetal kidney begins to occur at the onset of obstruction. Attempts to preserve renal function by antenatal interventions may best be achieved by early treatment

UR - http://www.ncbi.nlm.nih.gov/pubmed/18947615

U2 - 10.1016/j.jpurol.2006.05.007

DO - 10.1016/j.jpurol.2006.05.007

M3 - Article

VL - 2

SP - 216

EP - 224

JO - Journal of Pediatric Urology

JF - Journal of Pediatric Urology

SN - 1477-5131

IS - 4

ER -