Developmental Cell
Volume 56, Issue 16, 23 August 2021, Pages 2329-2347.e6
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Article
Metabolic plasticity drives development during mammalian embryogenesis

https://doi.org/10.1016/j.devcel.2021.07.020Get rights and content
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Highlights

  • Metabolomic analysis of metabolic plasticity during preimplantation development

  • Strong sensitivity to reductive stress in early embryos attenuates with maturity

  • Changes in redox balance controls metabolic plasticity in later-stage embryos

  • Myc reprograms embryonic glucose and glutamine metabolism to counter reductive stress

Summary

Mammalian preimplantation embryos follow a stereotypic pattern of development from zygotes to blastocysts. Here, we use labeled nutrient isotopologue analysis of small numbers of embryos to track downstream metabolites. Combined with transcriptomic analysis, we assess the capacity of the embryo to reprogram its metabolism through development. Early embryonic metabolism is rigid in its nutrient requirements, sensitive to reductive stress and has a marked disequilibrium between two halves of the TCA cycle. Later, loss of maternal LDHB and transcription of zygotic products favors increased activity of bioenergetic shuttles, fatty-acid oxidation and equilibration of the TCA cycle. As metabolic plasticity peaks, blastocysts can develop without external nutrients. Normal developmental metabolism of the early embryo is distinct from cancer metabolism. However, similarities emerge upon reductive stress. Increased metabolic plasticity with maturation is due to changes in redox control mechanisms and to transcriptional reprogramming of later-stage embryos during homeostasis or upon adaptation to environmental changes.

Keywords

preimplantation
redox
MYC
metabolic plasticity
embryo
developmental metabolism
zygotic genome activation
metabolic reprogramming
NAD+/NADH
reductive stress

Data and code availability

  • RNA-seq data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Microscopy data reported in this paper will be shared by the lead contact upon request.

  • No original code was generated in this study.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

6

These authors contributed equally

7

Lead contact