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

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.

Expression analysis of thg1l during Xenopus laevis development

“…indications of a potential involvement of thg1l in central nervous system (Cns) development have been also provided by microarray analyses in developing Xenopus laevis embryos, showing that thg1l is among the genes coherently regulated by the paired-like homeodomain transcription factor rax/rx1 (giudetti et al, 2014), a well-known critical factor for vertebrate retina specification and morphogenesis, which also plays a key role in brain development (terada et al, 2006). Finally, considering that dysregulations of mitochondrial function have an active role in the pathogenesis of several diseases, including neurodegenerative, cardiac, skeletal muscle disorders (Chen et al, 2023;schulz and schluter, 2023), as well as in embryo development (Bruna de lima et al, 2023;May-Panloup et al, 2021), clearly emerges the importance of research aimed at increasing knowledge about this gene. To our knowledge, the expression pattern of thg1l during embryogenesis is a topic that has been poorly investigated.…”