British Journal of Nutrition

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British Journal of Nutrition (2010), 103:1711-1719 Cambridge University Press
Copyright © The Authors 2010

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Molecular Nutrition

Maternal protein restriction with or without folic acid supplementation during pregnancy alters the hepatic transcriptome in adult male rats

Karen A. Lillycropa1 c1, Joanne Rodforda2, Emma S. Garratta2, Joanne L. Slater-Jefferiesa2, Keith M. Godfreya3, Peter D. Gluckmana4, Mark A. Hansona2 and Graham C. Burdgea2

a1 Development and Cell Biology, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
a2 Institute of Developmental Sciences, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
a3 Medical Research Council Epidemiology Resource Centre, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
a4 Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
Article author query
lillycrop ka [PubMed]  [Google Scholar]
rodford j [PubMed]  [Google Scholar]
garratt es [PubMed]  [Google Scholar]
slater-jefferies jl [PubMed]  [Google Scholar]
godfrey km [PubMed]  [Google Scholar]
gluckman pd [PubMed]  [Google Scholar]
hanson ma [PubMed]  [Google Scholar]
burdge gc [PubMed]  [Google Scholar]


Feeding pregnant rats a protein-restricted (PR) diet induces altered expression of candidate genes in the liver of the adult offspring, which can be prevented by supplementation of the PR diet with folic acid (PRF). We investigated the effect of maternal nutrition during pregnancy on the liver transcriptome in their adult male offspring. Pregnant rats were fed control, PR or PRF diets. Male offspring were killed on day 84. The liver transcriptome was analysed by microarray (six livers per maternal dietary group) followed by post hoc analysis of relative mRNA levels and gene ontology. These results were confirmed for selected genes by real-time RT-PCR. There were 311 genes that differed significantly ( ≥ 1·5-fold change; P < 0·05) between PR offspring (222 increased) and control offspring, while 191 genes differed significantly between PRF offspring (forty-five increased) compared with offspring of control dams. There were sixteen genes that were significantly altered in both PR and PRF offspring compared with controls. Ion transport, developmental process, and response to reactive oxygen species (RROS) and steroid hormone response (SHR) ontologies were altered in PR offspring. Folic acid supplementation prevented changes within RROS and SHR response pathways, but not in ion transport or developmental process. There was no effect of maternal PR on mRNA expression of imprinted genes. Insulin 1 and Pleckstrin homology-like domain family A member 2 were increased significantly in PRF compared with PR offspring. The present findings show that the pattern of induced changes in the adult liver transcriptome were dependent on maternal protein and folic acid intakes during pregnancy.

(Received August 04 2009)

(Revised December 09 2009)

(Accepted December 10 2009)

(Online publication March 09 2010)

Key Words:Transcriptome; Maternal diet; Microarray analysis; Protein restriction; Folate


c1 Corresponding author: Dr K. A. Lillycrop, fax +44 2380 594459, email


Abbreviations: GR, glucocorticoid receptor; Ins1, insulin 1; Phlda2, Pleckstrin homology-like domain family A member 2; PR, protein restricted; PRF, protein-restricted diet with folic acid