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

Author:
  • Graham Burdge
  • Samuel Hoile
  • Tobias Uller
  • Nicola Thomas
  • Peter Gluckman
  • Mark Hanson
  • Karen Lillycrop
Publishing year: 2011
Language: English
Publication/Series: PLoS ONE
Volume: 6
Document type: Journal article
Publisher: Public Library of Science

Abstract english

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.

Keywords

  • Biological Sciences

Other

Published
  • ISSN: 1932-6203
Tobias Uller
E-mail: tobias.uller [at] biol.lu.se

Professor

Evolutionary ecology

+46 46 222 30 94

E-C256

Sölvegatan 37, Lund

50

Research group

Experimental Evolution, Ecology & Behaviour

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I am currently about to move to Lund from University of Oxford. For details about DPhil students and postdocs in my previous research group based at the Edward Grey Institute, please click here

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CV (pdf; 241 kB)