Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy

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Abstract

There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7+/-23.3 vs. STZ 153.2+/-24.6, mean+/-SEM, p
Original languageEnglish
Article numbere58243
Number of pages9
JournalPLoS ONE
Volume8
Issue number3
DOIs
Publication statusPublished - 2013

Cite this

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title = "Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy",
abstract = "There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7+/-23.3 vs. STZ 153.2+/-24.6, mean+/-SEM, p",
author = "Stacey Hokke and James Armitage and {Puelles Rodriguez}, {Victor Guido} and Short, {Kieran Matthew} and Jones, {Lynelle Karyn} and Smyth, {Ian Macleod} and Bertram, {John Frederick} and Cullen-McEwen, {Luise Anne}",
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T1 - Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy

AU - Hokke, Stacey

AU - Armitage, James

AU - Puelles Rodriguez, Victor Guido

AU - Short, Kieran Matthew

AU - Jones, Lynelle Karyn

AU - Smyth, Ian Macleod

AU - Bertram, John Frederick

AU - Cullen-McEwen, Luise Anne

PY - 2013

Y1 - 2013

N2 - There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7+/-23.3 vs. STZ 153.2+/-24.6, mean+/-SEM, p

AB - There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7+/-23.3 vs. STZ 153.2+/-24.6, mean+/-SEM, p

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