Mitochondria in early development: linking the microenvironment, metabolism and the epigenome.

Mitochondria, originally of bacterial origin, are highly dynamic organelles that have evolved a symbiotic relationship within eukaryotic cells. Mitochondria undergo dynamic, stage-specific restructuring and redistribution during oocyte maturation and preimplantation embryo development, necessary to support key developmental events. Mitochondria also fulfil a wide range of functions beyond ATP synthesis, including the production of intracellular reactive oxygen species and calcium regulation, and are active participants in the regulation of signal transduction pathways. Communication between not only mitochondria and the nucleus, but also with other organelles, is emerging as a critical function which regulates preimplantation development. Significantly, perturbations and deficits in mitochondrial function manifest not only as reduced quality and/or poor oocyte and embryo development but contribute to post-implantation failure, long-term cell function and adult disease. A growing body of evidence indicates that altered availability of metabolic co-factors modulate the activity of epigenetic modifiers, such that oocyte and embryo mitochondrial activity and dynamics have the capacity to establish long-lasting alterations to the epigenetic landscape. It is proposed that preimplantation embryo development may represent a sensitive window during which epigenetic regulation by mitochondria is likely to have significant short- and long-term effects on embryo, and offspring, health. Hence, mitochondrial integrity, communication and metabolism are critical links between the environment, the epigenome and the regulation of embryo development.