The multi-omics regulatory landscape of human early embryogenesis.

Human early embryonic development relies on a highly coordinated regulatory network, which establishes the molecular foundation for individual life. These early events are closely associated with assisted reproductive outcomes, embryo quality assessment, and the etiology of developmental disorders. Although studies in model organisms such as mice have elucidated several key regulatory mechanisms, research on human embryos has progressed relatively slowly due to long-standing challenges in sample acquisition and ethical constraints. In recent years, advances in single-cell omics and high-throughput technologies for ultra-low-input samples, combined with the appropriate utilization of clinically discarded embryos-including parthenogenetic (PG), androgenetic (AG), tripronuclear (3PN), and normal bipronuclear (2PN) embryos-have enabled the systematic profiling of the transcriptomics, epigenomics, proteomics, and metabolomics during human early embryogenesis. This review summarizes the developmental potential and molecular characteristics of different embryo types, synthesizes key multi-omics findings on the regulation of human embryogenesis, and untangles the complex cooperation and imbalance between parental genomes in shaping cell fate decisions. Furthermore, we compare species-specific and shared regulatory mechanisms between humans and mice, providing a conceptual framework for constructing more physiologically relevant models of human early development.