Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development

This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable ener...

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Main Authors: Dunford, Louise J., Sinclair, Kevin D., Kwong, Wing Y., Sturrock, Craig, Clifford, Bethan L., Giles, Tom C., Gardner, David S.
Format: Article
Published: Federation of American Societies for Experimental Biology 2014
Online Access:https://eprints.nottingham.ac.uk/28886/
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author Dunford, Louise J.
Sinclair, Kevin D.
Kwong, Wing Y.
Sturrock, Craig
Clifford, Bethan L.
Giles, Tom C.
Gardner, David S.
author_facet Dunford, Louise J.
Sinclair, Kevin D.
Kwong, Wing Y.
Sturrock, Craig
Clifford, Bethan L.
Giles, Tom C.
Gardner, David S.
author_sort Dunford, Louise J.
building Nottingham Research Data Repository
collection Online Access
description This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet.
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spelling nottingham-288862020-05-04T20:12:50Z https://eprints.nottingham.ac.uk/28886/ Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development Dunford, Louise J. Sinclair, Kevin D. Kwong, Wing Y. Sturrock, Craig Clifford, Bethan L. Giles, Tom C. Gardner, David S. This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. Federation of American Societies for Experimental Biology 2014-11 Article PeerReviewed Dunford, Louise J., Sinclair, Kevin D., Kwong, Wing Y., Sturrock, Craig, Clifford, Bethan L., Giles, Tom C. and Gardner, David S. (2014) Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development. FASEB journal, 28 (11). pp. 4880-4892. ISSN 0892-6638 http://www.fasebj.org/content/28/11/4880 doi:10.1096/fj.14-255364 doi:10.1096/fj.14-255364
spellingShingle Dunford, Louise J.
Sinclair, Kevin D.
Kwong, Wing Y.
Sturrock, Craig
Clifford, Bethan L.
Giles, Tom C.
Gardner, David S.
Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
title Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
title_full Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
title_fullStr Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
title_full_unstemmed Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
title_short Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
title_sort maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development
url https://eprints.nottingham.ac.uk/28886/
https://eprints.nottingham.ac.uk/28886/
https://eprints.nottingham.ac.uk/28886/