Metaboloepigenetics: providing alternate hypotheses for regulation of gene expression in the early embryo

ABSTRACT

The metabolic and epigenetic landscapes of the pre-implantation embryo change and evolve rapidly as the embryo travels through the reproductive tract. The maternal and paternal genomes combine, rapid cell division is initiated, potency is re-established and eventually differentiation begins, all in the absence of a vascular supply delivering oxygen, nutrients and a functional waste removal system. In recent years, it has become clear that environmental challenges to the developing embryo, including maternal diet, stress and inflammation, alter its long-term trajectory, although the exact signaling molecules, which are recognised by the embryo, and the mechanisms by which these signals are translated into long-term outcomes, remain elusive. Recently, it has become apparent that energy or fuel-sensing metabolic pathways interact with important epigenetic regulators of chromatin structure, to regulate gene expression. While this has not yet been explored in the pre-implantation embryo, the interaction between these two key cellular systems, - metaboloepigenetics - is a plausible mechanism by which gene-environment interactions occur, and by which the embryo’s trajectory is established. This review explores the metabolic and epigenetic plasticity of the early embryo, and how the two systems intertwine to propagate the next generation.