Comparative proteomic landscapes provide insights into mammalian preimplantation development

Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our Comprehensive Solution of Ultrasensitive Proteome Technology to measure the proteomic profiles of oocytes and early embryos, and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) stages between the two species. Integrative analysis with translatome data revealed extensive divergence between translation and protein levels. Multi-omic analysis indicated that ZGA transcripts contribute to protein accumulation in blastocysts. Consequently, we identified several transcriptional regulators critical for early development in mice, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics (SEP) of poor quality embryos from over 100 patient-couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening new avenues for addressing human infertility.