Non-genetic inheritance allows the environmental history of an individual to influence the next generation. Observational evidence in mammals suggests two forms of non-genetic transgenerational effects; ‘developmental programming’ in response to early life exposures and germ-line transmission of an environmentally induced change i.e. ‘epigenetic inheritance’. However, at present the mechanistic basis of these phenomena in mammals remains mysterious.
We have developed a mammalian model encompassing both of these forms of inheritance. Inbred, C57BL/6J female mice are fed either a protein restricted or standard diet through gestation/lactation. The F1 offspring represent ‘developmentally programmed’ individuals. F1 males are maintained on control diet post-weaning and then mated to produce F2 offspring; our model for germ-line ‘epigenetic inheritance’.
We find that both F1 and F2 adults show phenotypic and molecular changes. However, it is likely that many of these observations relate to downstream effects. What then, is the primary cause of this altered developmental trajectory? Our current work aims to define the primary phenotype in our model of mammalian epigenetic inheritance and correlate this with epigenetic perturbations in the male germ-line. To this end, transcriptomic analyses are being performed on F2 animals at multiple stages of development; prior to the first embryonic cellular differentiation, late gestation and as adults. Our recent findings will be discussed.