Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations
Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations
Epidemiological studies and experimental models show that maternal nutritional constraint during pregnancy alters the metabolic phenotype of the offspring and that this can be passed to subsequent generations. In the rat, induction of an altered metabolic phenotype in the liver of the F1 generation by feeding a protein-restricted diet (PRD) during pregnancy involves the altered methylation of specific gene promoters. We therefore investigated whether the altered methylation of PPARalpha and glucocorticoid receptor (GR) promoters was passed to the F2 generation. Females rats (F0) were fed a reference diet (180 g/kg protein) or PRD (90 g/kg protein) throughout gestation, and AIN-76A during lactation. The F1 offspring were weaned onto AIN-76A. F1 females were mated and fed AIN-76A throughout pregnancy and lactation. F1 and F2 males were killed on postnatal day 80. Hepatic PPARalpha and GR promoter methylation was significantly (P<0 x 05) lower in the PRD group in the F1 (PPARalpha 8 %, GR 10 %) and F2 (PPARalpha 11 %, GR 8 %) generations. There were trends (P<0 x 1) towards a higher expression of PPARalpha, GR, acyl-CoA oxidase and phosphoenolpyruvate carboxykinase (PEPCK) in the F1 and F2 males, although this was significant only for PEPCK. These data show for the first time that the altered methylation of gene promoters induced in the F1 generation by maternal protein restriction during pregnancy is transmitted to the F2 generation. This may represent a mechanism for the transmission of induced phenotypes between generations.
435-439
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Slater-Jefferies, Jo
e46c711a-9d4c-436a-b853-828df69bb4d7
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Phillips, Emma S.
36b8c608-f279-4239-87c0-32df46ced0c7
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
March 2007
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Slater-Jefferies, Jo
e46c711a-9d4c-436a-b853-828df69bb4d7
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Phillips, Emma S.
36b8c608-f279-4239-87c0-32df46ced0c7
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C., Slater-Jefferies, Jo, Torrens, Christopher, Phillips, Emma S., Hanson, Mark A. and Lillycrop, Karen A.
(2007)
Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations.
British Journal of Nutrition, 97 (3), .
(doi:10.1017/S0007114507352392).
Abstract
Epidemiological studies and experimental models show that maternal nutritional constraint during pregnancy alters the metabolic phenotype of the offspring and that this can be passed to subsequent generations. In the rat, induction of an altered metabolic phenotype in the liver of the F1 generation by feeding a protein-restricted diet (PRD) during pregnancy involves the altered methylation of specific gene promoters. We therefore investigated whether the altered methylation of PPARalpha and glucocorticoid receptor (GR) promoters was passed to the F2 generation. Females rats (F0) were fed a reference diet (180 g/kg protein) or PRD (90 g/kg protein) throughout gestation, and AIN-76A during lactation. The F1 offspring were weaned onto AIN-76A. F1 females were mated and fed AIN-76A throughout pregnancy and lactation. F1 and F2 males were killed on postnatal day 80. Hepatic PPARalpha and GR promoter methylation was significantly (P<0 x 05) lower in the PRD group in the F1 (PPARalpha 8 %, GR 10 %) and F2 (PPARalpha 11 %, GR 8 %) generations. There were trends (P<0 x 1) towards a higher expression of PPARalpha, GR, acyl-CoA oxidase and phosphoenolpyruvate carboxykinase (PEPCK) in the F1 and F2 males, although this was significant only for PEPCK. These data show for the first time that the altered methylation of gene promoters induced in the F1 generation by maternal protein restriction during pregnancy is transmitted to the F2 generation. This may represent a mechanism for the transmission of induced phenotypes between generations.
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Published date: March 2007
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Local EPrints ID: 44168
URI: http://eprints.soton.ac.uk/id/eprint/44168
ISSN: 0007-1145
PURE UUID: 89af5976-80b6-4ec3-aac4-1adf9f3f893e
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Date deposited: 21 Feb 2007
Last modified: 16 Mar 2024 03:50
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Author:
Christopher Torrens
Author:
Emma S. Phillips
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