Dietary protein restriction during F(0) pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring

Hoile, Samuel P., Lillycrop, Karen A., Thomas, Nicola A., Hanson, Mark A. and Burdge, Graham C. (2011) Dietary protein restriction during F(0) pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring. PLoS ONE, 6, (7), e21668-[14pp]. (doi:10.1371/journal.pone.0021668). (PMID:21750721).


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There is considerable evidence for non-genomic transmission between generations of phenotypes induced by environmental exposures during development, although the mechanism is poorly understood. We investigated whether alterations in expression of the liver transcriptome induced in F1 offspring by feeding F0 dams a protein-restricted (PR) diet during pregnancy were passed with or without further change to two subsequent generations. The number of genes that differed between adult female offspring of F0 protein-restricted (PR) and protein-sufficient (PS) dams was F1 1,684 genes, F2 1,680 and F3 2,062. 63/113 genes that were altered in all three generations showed directionally opposite differences between generations. There was a trend toward increased proportions of up-regulated genes in F3 compared to F1. KEGG analysis showed that only the Adherens Junctions pathway was altered in all three generations. PR offspring showed altered fasting glucose homeostasis and changes in phosphoenolpyruvate carboxykinase promoter methylation and expression in all three generations. These findings show that dietary challenge during F0 pregnancy induced altered gene expression in all three generations, but relatively few genes showed transmission of altered expression between generations. For the majority of altered genes, these changes were not found in all generations, including some genes that were changed in F3 but not F1, or the direction and magnitude of difference between PR and PS differed between generations. Such variation may reflect differences between generations in the signals received by the fetus from the mother as a consequence of changes in the interaction between her phenotype and the environment

Item Type: Article
Digital Object Identifier (DOI): doi:10.1371/journal.pone.0021668
ISSNs: 1932-6203 (print)
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions : University Structure - Pre August 2011 > School of Biological Sciences
University Structure - Pre August 2011 > School of Medicine
ePrint ID: 193477
Accepted Date and Publication Date:
7 July 2011Published
Date Deposited: 14 Jul 2011 11:19
Last Modified: 31 Mar 2016 13:43
Epigenetic processes in transmission of prenatally-induced phenotypes between generations
Funded by: BBSRC (BB/F013043/1)
Led by: Graham Charles Burdge
16 June 2008 to 15 June 2011

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