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Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition
Graham C Burdge1, Samuel P Hoile, Tobias Uller
1Academic Unit of Human Development and Health, Faculty of Medicine, Institute of Developmental Sciences, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. g.c.burdge@southampton.ac.uk
Plos One
|December 6, 2011
Summary
Environmental challenges induce epigenetic changes that alter phenotypes across generations. These epigenetic marks appear to be newly established in each generation, not directly inherited.
Area of Science:
- Epigenetics and developmental biology
- Transgenerational inheritance
- Environmental epigenomics
Background:
- Epigenetic modifications mediate developmental plasticity in response to environmental cues.
- Phenotypic traits can be transmitted across generations via epigenetic mechanisms.
- Distinguishing between direct epigenetic inheritance and de novo induction is crucial.
Purpose of the Study:
- To investigate the role of epigenetic changes in transgenerational phenotypic alterations.
- To determine if epigenetic marks are directly transmitted or induced de novo across generations.
- To examine the impact of a sustained environmental challenge on epigenetic regulation of energy metabolism.
Main Methods:
- Exposure of rats to a 25% increased dietary energy intake from conception through F3 generation.
- Measurement of epigenetic marks, gene expression (PEPCK, PPARα, carnitine palmitoyl transferase-1, Dnmt1, Dnmt3a2, Dnmt3b), and metabolic parameters (plasma glucose, β-hydroxybutyrate) across four generations.
- Analysis of DNA methylation patterns in the promoter region of the PEPCK gene.
Main Results:
- Maternal phenotype, including weight gain and metabolic markers, was influenced by the preceding generation's phenotype and the current pregnancy environment.
- Altered expression of genes involved in energy metabolism (PEPCK, PPARα, carnitine palmitoyl transferase-1) was observed.
- PEPCK mRNA expression correlated inversely with promoter methylation, and DNA methyltransferase 3a2 expression increased with decreased promoter methylation across generations.
Conclusions:
- Transgenerational effects on phenotype are influenced by maternal phenotype and environmental factors.
- Altered DNA methylation patterns suggest de novo induction of epigenetic marks in each generation.
- Epigenetic regulation of energy metabolism exhibits transgenerational plasticity in response to environmental challenges.
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