Charting morphotoxicity with complementary embryo models

Traditional toxicity testing methods, relying on animal models or simplified 2D cell cultures, inherently overlook the nuanced interplay between distinct developmental stages and cell lineages. Addressing this gap, we present an innovative high-throughput screening approach leveraging three complementary 3D stem cell-based embryo models: pre-implantation stage blastoids, and early post-implantation stage epiblast-like (EPICs) and amnion-like clusters (AMNICs).

Cultured in thermoformed microwell arrays, these models were systematically exposed to a library of 27 widely used compounds. Automated image-based analyses allowed for precise quantification of morphotoxic effects. Key findings include the identification of compounds such as ascorbic acid and valproic acid, which demonstrated distinct and opposing effects across the different embryo models, highlighting developmental stage-specific sensitivities.