Maternal Proteomic Polarity Defines the Spatial Coordinates for Mammalian Embryonic Patterning
The mechanisms underlying early symmetry-breaking events in mammalian lineage specification remain to be fully elucidated. By integrating a graph theory framework with single cell metabolic transcriptomic dual omics, spatial proteomics, and quantitative mitochondrial profiling, our data suggest that the maternal proteome of MII oocytes may exhibit an animal vegetal axis: bioenergetic components, including mitochondria and respiratory enzyme complexes (MREs), appear enriched at the animal pole, whereas the vegetal pole displays characteristics of active biosynthesis. We observed that this asymmetry seems to be unequally partitioned during the first cleavage; blastomeres inheriting a larger proportion of animal-pole cytoplasm show a bias toward trophectoderm differentiation (TEbB), hinting at a pre existing gradient for fate determination within the embryo. Furthermore, maternal bioenergetic protein levels in TEbB cells appear to be supplemented by newly transcribed MREs during zygotic genome activation (ZGA), suggesting a metabolic relay from maternal to zygotic control. These findings suggest that the spatial architecture of mammalian development may be initially established prior to fertilization through asymmetric maternal inheritance.