Dynamic metabolism is exhibited by early mammalian embryos to support changing cell fates during development. It is widely acknowledged that metabolic pathways not only satisfy cellular energetic demands, but also play pivotal roles in the process of cell signalling, gene regulation, cell proliferation and differentiation. Recently, various new technological advances have been made in metabolomics and computational analysis, deepening our understanding of the crucial role of dynamic metabolism during early mammalian embryogenesis. In this Review, we summarize recent studies on oocyte and embryo metabolism and its regulation, with a particular focus on its association with key developmental events such as fertilization, zygote genome activation and cell fate determination. In addition, we discuss the mechanisms of certain metabolites that, in addition to serving as energy sources, contribute to epigenetic modifications.
The metabolic landscape of the post-implantation mouse embryo and its associated placenta remains incompletely characterised. Here, we performed untargeted LC–MS-based metabolomics on mouse embryos from E9.5 to E13.5 and on placentas from E10.5 to E12.5, and integrated these data with a published single-cell transcriptomic atlas of the same developmental window. We found that the embryonic metabolome undergoes progressive remodelling, with the most pronounced changes occurring around E11.5. By combining time-course analysis, WGCNA-based network prioritisation, and embryo–placenta comparison, we identified 56 core metabolites that increased coordinately in both tissues during this period. Single-cell analysis revealed that the definitive erythroid lineage was enriched for nicotinate and nicotinamide metabolism, with progressive upregulation of the NAD+ biosynthetic enzyme Nmnat2 during erythroid maturation. Correspondingly, niacinamide, NAD, and 1-methylnicotinamide increased in the embryo from E10.5 to E13.5. Regulon analysis showed that haematopoiesis-related transcriptional programmes, including Spi1 and Gfi1, correlated with development-associated metabolic modules. Together, our data provide a stage-resolved metabolomic resource and identify candidate metabolites that may support embryo growth in vitro.