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

Burdge, Graham; Hoile, Samuel; Uller, Tobias LU ; Thomas, Nicola; Gluckman, Peter; Hanson, Mark and Lillycrop, Karen (2011) In PLoS One 6.
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... (More)
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 beta-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARalpha 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. (Less)
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published
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in
PLoS One
volume
6
publisher
Public Library of Science
external identifiers
  • Scopus:82355183890
ISSN
1932-6203
DOI
10.1371/journal.pone.0028282
language
English
LU publication?
no
id
e4dd7dc4-402f-4ba1-91d6-9c32e8c627d4 (old id 4739001)
date added to LUP
2014-11-10 11:29:31
date last changed
2016-10-13 04:35:17
@misc{e4dd7dc4-402f-4ba1-91d6-9c32e8c627d4,
  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 beta-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARalpha 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.},
  author       = {Burdge, Graham and Hoile, Samuel and Uller, Tobias and Thomas, Nicola and Gluckman, Peter and Hanson, Mark and Lillycrop, Karen},
  issn         = {1932-6203},
  language     = {eng},
  publisher    = {ARRAY(0x8f110f0)},
  series       = {PLoS One},
  title        = {Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition},
  url          = {http://dx.doi.org/10.1371/journal.pone.0028282},
  volume       = {6},
  year         = {2011},
}