Environmental nano-particulates induced pre-implantation embryonic toxicity in pluripotent stem cell-derived blastoids

Human pre-implantation embryonic development is challenged by raising environmental pollution such as nano-sized carbon black and emerging nanoplastics. However, the absence of an Exposome research model still handles our understanding of nano-sized pollutants caused early embryonic toxicity. Notably, the cutting-edge blastoids constructed from pluripotent stem cells could be a high-throughput research model to fill this knowledge gap. Our team develops a blastoids platform from primate pluripotent stem cells. Here in this study we employed the blastoids to assess the embryonic toxicity of environmental nano-sized particulate pollutants: emerging nano-polystyrene and general nano-carbon black. We observed that both pollutants impaired blastoid structure and cell lineage specification. Leveraging 10X scRNA-seq and DIA-MS, we constructed a multi-layered, multi-dimensional early embryonic Exposome dataset encompassing information at cellular (blastoids self-organization, cell chatting), subcellular organelles and molecular (gene expression, protein corona adsorption) levels, as well as exposure dose gradients. We also provided three subsets regarding gene linear expression of lipid metabolism, developmental signaling and DNA repairing of blastoids. We identified novel trophoblast cell populations and molecular events that linearly correlated with exposure dosages, clarified the convergence and divergence of exposure effects between emerging and general pollutants, and experimentally validated the disturbance of nano-particles on lipid droplets, early embryonic signaling and genomic stabilization. In summary, our study provides an early embryonic Exposome database in the context of nano-sized environmental particulate pollution, meanwhile underscores blastoids as a robust tool for early embryonic toxicity investigation.