DOHaD: A Menagerie of Adaptations and Perspectives: The interplay between early embryo metabolism and mitoepigenetic programming of development

Abstract

In brief This review discusses advances in the knowledge of epigenetic mechanisms regulating mitochondrial DNA and the relationship with reproductive biology. Abstract Initially perceived simply as an ATP producer, mitochondria also participate in a wide range of other cellular functions. Mitochondrial communication with the nucleus, as well as signaling to other cellular compartments, is critical to cell homeostasis. Therefore, during early mammalian development, mitochondrial function is reported as a key element for survival. Any mitochondrial dysfunction may reflect in poor oocyte quality and may impair embryo development with possible long-lasting consequences to cell functions and the overall embryo phenotype. Growing evidence suggests that the availability of metabolic modulators can alter the landscape of epigenetic modifications in the nuclear genome providing an important layer for the regulation of nuclear-encoded gene expression. However, whether mitochondria could also be subjected to such similar epigenetic alterations and the mechanisms involved remain largely obscure and controversial. Mitochondrial epigenetics, also known as ‘mitoepigenetics’ is an intriguing regulatory mechanism in mitochondrial DNA (mtDNA)-encoded gene expression. In this review, we summarized the recent advances in mitoepigenetics, with a special focus on mtDNA methylation in reproductive biology and preimplantation development. A better comprehension of the regulatory role of mitoepigenetics will help the understanding of mitochondrial dysfunction and provide novel strategies for in vitro production systems and assisted reproduction technologies, as well as prevent metabolic related stress and diseases.