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Metabolic plasticity drives development during mammalian embryogenesis.

Developmental cell (2021-08-25)
Mark S Sharpley, Fangtao Chi, Johanna Ten Hoeve, Utpal Banerjee
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
UK-5099, ≥98% (HPLC)
Sigma-Aldrich
L-Methionine sulfoximine, suitable for cell culture
Sigma-Aldrich
O-(Carboxymethyl)hydroxylamine hemihydrochloride, 98%
Sigma-Aldrich
(+)-Etomoxir sodium salt hydrate, ≥98% (HPLC), powder
Sigma-Aldrich
Chorionic gonadotropin human, lyophilized powder, vial of ~10,000 IU