Erasing gametes to write blastocysts: metabolism as the new player in epigenetic reprogramming

Abstract

Understanding preimplantation embryonic development is crucial for the improvement of assisted reproductive technologies and animal production. To achieve this goal, it is important to consider that gametes and embryos are highly susceptible to environmental changes. Beyond the metabolic adaptation, the dynamic status imposed during follicular growth and early embryogenesis may create marks that will guide the molecular regulation during prenatal development, and consequently impact the offspring phenotype. In this context, metaboloepigenetics has gained attention, as it investigates the crosstalk between metabolism and molecular control, i.e., how substrates generated by metabolic pathways may also act as players of epigenetic modifications. In this review, we present the main metabolic and epigenetic events of pre-implantation development, and how these systems connect to open possibilities for targeted manipulation of reproductive technologies and animal production systems.

Dynamic Changes in the Proteome of Early Bovine Embryos Developed In Vivo

“…During the first cleavage divisions, mammalian embryos, including bovine, use mostly pyruvate and amino acids as preferred substrates, which are metabolized through the TCA cycle and oxidative phosphorylation to produce energy ( Khurana and Niemann, 2000 ; Li and Winuthayanon, 2017 ). At the time of compaction, the demand for energy and biomass increases and glucose is metabolized with greater efficiency through the pentose phosphate pathway (PPP), important for the biosynthesis of nucleotides, and the glycolysis pathway in addition to the TCA cycle ( Milazzotto et al, 2020 ). Furthermore, substrates generated by metabolism seem to be important players in epigenetic modifications in preimplantation embryos ( Ispada et al, 2020 ; Milazzotto et al, 2020 ).…”

“…At the time of compaction, the demand for energy and biomass increases and glucose is metabolized with greater efficiency through the pentose phosphate pathway (PPP), important for the biosynthesis of nucleotides, and the glycolysis pathway in addition to the TCA cycle ( Milazzotto et al, 2020 ). Furthermore, substrates generated by metabolism seem to be important players in epigenetic modifications in preimplantation embryos ( Ispada et al, 2020 ; Milazzotto et al, 2020 ).…”

Mining RNAseq data reveals dynamic metaboloepigenetic profiles in human, mouse and bovine pre-implantation embryos

“…As aptly stated by ( Harvey et al., 2016 ), “metabolism is at the heart of cell-sensing mechanisms”. Beyond simply providing ATP to maintain homeostasis and cell replication, metabolism generates intermediate products that form the basic building blocks for cell proliferation, and modulate signaling pathways and gene expression (reviewed by Donohoe and Bultman, 2012 ; Harvey et al., 2016 ; Milazzotto et al., 2020 ; Spyrou et al., 2019 ). Further, metabolites have the capacity to regulate the cellular epigenome, inducing long-term changes to cells via a process known as metaboloepigenetic regulation ( Donohoe and Bultman, 2012 ).…”

Silencing mark H3K27me3 is differently reprogrammed in bovine embryos with distinct kinetics of development

“…Epigenetic marks are responsible for the control of gene expression and include DNA methylation and histone post‐translational modifications (PTMs) (Milazzotto, 2020). Regarding embryo kinetics, fast embryos have an overall greater presence of silencing marks, such as DNA methylation (Ispada, 2020) and trimethylation of lysine 9 at histone H3 (H3K9me3) (Ispada, 2021).…”