Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the promotor of the offspring
Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the promotor of the offspring
Induction of an altered phenotype by prenatal under-nutrition involves changes in the epigenetic regulation of specific genes. We investigated the effect of feeding pregnant rats a protein-restricted (PR) diet with different amounts of folic acid on the methylation of individual CpG dinucleotides in the hepatic PPAR? promoter in juvenile offspring, and the effect of the maternal PR diet on CpG methylation in adult offspring. Pregnant rats (five per group) were fed 180 g/kg casein (control) or 90 g/kg casein with 1 mg/kg folic acid (PR), or 90 g/kg casein and 5 mg/kg folic acid (PRF). Offspring were killed on postnatal day 34 (five males and females per group) and day 80 (five males per group). Methylation of sixteen CpG dinucleotides in the PPAR? promoter was measured by pyrosequencing. Mean PPAR? promoter methylation in the PR offspring (4·5 %) was 26 % lower than controls (6·1 %) due to specific reduction at CpG dinucleotides 2 (40 %), 3 (43 %), 4 (33 %) and 16 (48 %) (P < 0·05). There was no significant difference in methylation at these CpG between control and PRF offspring. Methylation of CpG 5 and 8 was higher (47 and 63 %, respectively, P < 0·05) in the PRF offspring than control or PR offspring. The methylation pattern in day 80 PR offspring was comparable to day 34 PR offspring. These data show for the first time that prenatal nutrition induces differential changes to the methylation of individual CpG dinucleotides in juvenile rats which persist in adults.
fetal programming, epigenetic regulation, rats, PPAR?
278-282
Lillycrop, Karen A.
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Phillips, Emma S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Torrens, Christopher
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Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Jackson, Alan A.
c9a12d7c-b4d6-4c92-820e-890a688379ef
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
August 2008
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Phillips, Emma S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Jackson, Alan A.
c9a12d7c-b4d6-4c92-820e-890a688379ef
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Lillycrop, Karen A., Phillips, Emma S., Torrens, Christopher, Hanson, Mark A., Jackson, Alan A. and Burdge, Graham C.
(2008)
Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the promotor of the offspring.
British Journal of Nutrition, 100 (2), .
(doi:10.1017/S0007114507894438).
(PMID:18186951)
Abstract
Induction of an altered phenotype by prenatal under-nutrition involves changes in the epigenetic regulation of specific genes. We investigated the effect of feeding pregnant rats a protein-restricted (PR) diet with different amounts of folic acid on the methylation of individual CpG dinucleotides in the hepatic PPAR? promoter in juvenile offspring, and the effect of the maternal PR diet on CpG methylation in adult offspring. Pregnant rats (five per group) were fed 180 g/kg casein (control) or 90 g/kg casein with 1 mg/kg folic acid (PR), or 90 g/kg casein and 5 mg/kg folic acid (PRF). Offspring were killed on postnatal day 34 (five males and females per group) and day 80 (five males per group). Methylation of sixteen CpG dinucleotides in the PPAR? promoter was measured by pyrosequencing. Mean PPAR? promoter methylation in the PR offspring (4·5 %) was 26 % lower than controls (6·1 %) due to specific reduction at CpG dinucleotides 2 (40 %), 3 (43 %), 4 (33 %) and 16 (48 %) (P < 0·05). There was no significant difference in methylation at these CpG between control and PRF offspring. Methylation of CpG 5 and 8 was higher (47 and 63 %, respectively, P < 0·05) in the PRF offspring than control or PR offspring. The methylation pattern in day 80 PR offspring was comparable to day 34 PR offspring. These data show for the first time that prenatal nutrition induces differential changes to the methylation of individual CpG dinucleotides in juvenile rats which persist in adults.
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Published date: August 2008
Keywords:
fetal programming, epigenetic regulation, rats, PPAR?
Organisations:
Dev Origins of Health & Disease
Identifiers
Local EPrints ID: 152231
URI: http://eprints.soton.ac.uk/id/eprint/152231
ISSN: 0007-1145
PURE UUID: 1d5ccdd1-fb29-4351-bd70-9810c7fbdd88
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Date deposited: 13 May 2010 15:16
Last modified: 14 Mar 2024 02:44
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Author:
Emma S. Phillips
Author:
Christopher Torrens
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