Establishment of a developmental toxicity assay based on human iPSC reporter to detect FGF signal disruption

The number of man-made chemicals has increased exponentially recently, and exposure to some of them can induce fetal malformations. Because complex and precisely programmed signaling pathways play important roles in develop-mental processes, their disruption by external chemicals often triggers develop-mental toxicity. However, highly accurate and high-throughput screening assays for potential developmental toxicants are currently lacking. In this study, we pro-pose a reporter assay that utilizes human-induced pluripotent stem cells (iPSCs) to detect changes in fibroblast growth factor signaling, which is essential for limb morphogenesis. The dynamics of this signaling after exposure to a chemical were integrated to estimate the degree of signaling disruption, which afforded a good prediction of the capacity of chemicals listed in the ECVAM International Validation Study that induce limb malformations. This study presents an initial report of a human iPSC-based signaling disruption assay, which could be useful for the screening of potential developmental toxicants.

Automated summary

The number of man-made chemicals has been increasing rapidly in recent years, and some of these chemicals can cause fetal malformations. Disruption of complex and precisely programmed signaling pathways by external chemicals often leads to developmental toxicity. However, there is currently a lack of highly accurate and high-throughput screening assays for potential developmental toxicants. In this study, a reporter assay based on human-induced pluripotent stem cells (iPSCs) was proposed to detect changes in fibroblast growth factor signaling, which is crucial for limb morphogenesis. This assay successfully predicted the capacity of chemicals to induce limb malformations.