Comparative proteomic landscapes elucidate human preimplantation development and failure.

Area of Science:

• Proteomics
• Developmental Biology
• Genomics

Background:

• Mammalian preimplantation development is crucial for reproduction.
• Understanding proteomic changes during this stage, especially in humans, is limited.

Purpose of the Study:

• To comprehensively analyze proteomic profiles of human and mouse oocytes and early embryos.
• To investigate proteomic dynamics around zygotic genome activation (ZGA).
• To identify factors contributing to preimplantation development failure and human infertility.

Main Methods:

• Ultrasensitive proteomic technology applied to oocytes and early embryos.
• Integrative analysis with translatomic data.
• Multi-omic analysis including single-embryo proteomics of poor-quality embryos.

Main Results:

• Identified nearly 8,000 human and over 6,300 mouse proteins.
• Observed distinct proteomic dynamics and divergence between translation and protein accumulation around ZGA.
• Linked ZGA transcripts to protein accumulation and identified key transcriptional regulators in mouse embryos.
• Provided insights into preimplantation development failure using single-embryo proteomics.

Conclusions:

• Mammalian preimplantation development exhibits species-specific proteomic dynamics.
• ZGA plays a critical role in early embryonic development and lineage specification.
• Proteomic insights can illuminate causes of human infertility and developmental failure.