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Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition

Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition
Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition
Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and ?-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPAR? and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation
1932-6203
e28282
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Uller, Tobias
05ac1f63-5fd6-490d-8f9f-f7d3ed62b948
Thomas, Nicola A.
326aecd5-a0cc-40ae-895e-eeaa39cadda2
Gluckman, Peter D.
ef2e8b92-0b76-4a12-bd7c-01b0674f94d3
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Uller, Tobias
05ac1f63-5fd6-490d-8f9f-f7d3ed62b948
Thomas, Nicola A.
326aecd5-a0cc-40ae-895e-eeaa39cadda2
Gluckman, Peter D.
ef2e8b92-0b76-4a12-bd7c-01b0674f94d3
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc

Burdge, Graham C., Hoile, Samuel P., Uller, Tobias, Thomas, Nicola A., Gluckman, Peter D., Hanson, Mark A. and Lillycrop, Karen A. (2011) Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition. PLoS ONE, 6 (11), e28282. (doi:10.1371/journal.pone.0028282). (PMID:22140567)

Record type: Article

Abstract

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and ?-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPAR? and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation

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Published date: November 2011
Organisations: Human Development & Health

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Local EPrints ID: 337142
URI: http://eprints.soton.ac.uk/id/eprint/337142
ISSN: 1932-6203
PURE UUID: f0c8270c-df47-4fe7-93c5-a46fd482865a
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489

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Date deposited: 19 Apr 2012 13:28
Last modified: 15 Mar 2024 03:07

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Contributors

Author: Samuel P. Hoile
Author: Tobias Uller
Author: Nicola A. Thomas
Author: Peter D. Gluckman
Author: Mark A. Hanson ORCID iD

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