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

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).


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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

Item Type: Article
Digital Object Identifier (DOI): doi:10.1371/journal.pone.0028282
ISSNs: 1932-6203 (print)
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QP Physiology
Divisions : Faculty of Medicine > Human Development and Health
ePrint ID: 337142
Accepted Date and Publication Date:
November 2011Published
Date Deposited: 19 Apr 2012 13:28
Last Modified: 31 Mar 2016 14:26
Epigenetic processes in transmission of prenatally-induced phenotypes between generations
Funded by: BBSRC (BB/F013043/1)
Led by: Graham Charles Burdge
16 June 2008 to 15 June 2011

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