Postdoctoral Institute of Zoology (IOZ), Chinese Academy of Sciences (CAS), China
Abstract: Mammalian placental metabolism is crucial for placental and embryonic development. Yet the stage-specific metabolic dynamics governing placentation remain poorly characterized. Here, we conducted integrated metabolomic-transcriptomic profiling of 501 mouse placentas across embryonic days (E) 8.5-14.5 and revealed the key metabolic characteristics of placentation. Our multi-omics approach revealed three distinct developmental phases (E8.5, E9.5-10.5, E11.5-14.5) with transitional periods at E8.5-9.5 and E10.5-11.5. Phase-specific metabolic signatures emerged: ubiquinone biosynthesis dominated E8.5, riboflavin/phenylalanine pathways marked E9.5-10.5, while glycine/serine/nucleotide metabolism prevailed post-E11.5. Based on a series of metabolite and enrichment analyses, we identified 1,4-dihydronicotinamide adenine dinucleotide (NADH) as a central regulator. Using IVC embryos, we found that NADH promoted body length extension. Mechanistically, presomitic mesoderm (PSM) -like cells treated with NADH showed an elevated total NAD+/NADH ratio, increased generation of reactive oxygen species (ROS), and accelerated cell proliferation. Together, our findings reveal the role of placental metabolites, which might provide mechanistic insights for optimizing placenta organoids and IVC embryos or embryoids.
Funding Source: This work was financially supported by the National Natural Science Foundation of China (82402032), the Postdoctoral Fellowship Program of CPSF (GZB20240738).
