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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.

Authors

Louise J. Dunford

KEVIN SINCLAIR kevin.sinclair@nottingham.ac.uk
Professor of Developmental Biology

Wing Y. Kwong

Bethan L. Clifford

Tom C. Giles



Abstract

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.

Citation

Dunford, L. J., Sinclair, K. D., Kwong, W. Y., Sturrock, C., Clifford, B. L., Giles, T. C., & Gardner, D. 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), 4880-4892. https://doi.org/10.1096/fj.14-255364

Journal Article Type Article
Acceptance Date Jul 30, 2014
Online Publication Date Jul 30, 2014
Publication Date 2014-11
Deposit Date Jul 21, 2015
Publicly Available Date Jul 21, 2015
Journal FASEB journal
Print ISSN 0892-6638
Electronic ISSN 1530-6860
Publisher Federation of American Society of Experimental Biology
Peer Reviewed Peer Reviewed
Volume 28
Issue 11
Pages 4880-4892
DOI https://doi.org/10.1096/fj.14-255364
Public URL http://eprints.nottingham.ac.uk/id/eprint/28886
Publisher URL http://www.fasebj.org/content/28/11/4880
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development (1.8 Mb)
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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