Dietary protein restriction during F(0) pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring
Dietary protein restriction during F(0) pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring
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
e21668-[14pp]
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Thomas, Nicola A.
326aecd5-a0cc-40ae-895e-eeaa39cadda2
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
7 July 2011
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Thomas, Nicola A.
326aecd5-a0cc-40ae-895e-eeaa39cadda2
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
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), .
(doi:10.1371/journal.pone.0021668).
(PMID:21750721)
Abstract
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
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Published date: 7 July 2011
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Local EPrints ID: 193477
URI: http://eprints.soton.ac.uk/id/eprint/193477
ISSN: 1932-6203
PURE UUID: 77a1ee09-5bd4-475d-9807-3e57776961ab
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Date deposited: 14 Jul 2011 11:19
Last modified: 15 Mar 2024 03:07
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Author:
Samuel P. Hoile
Author:
Nicola A. Thomas
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