Prediction of embryotoxic potential using the ReProGlo stem cell-based Wnt reporter assay

• The ReProGlo assay is an in vitro tool to predict embryotoxic effects of chemicals.
• We extended our test data base from 17 to 80 compounds.
• We introduce a new classification scheme including a group of “unspecific positives”.
• We compared our results with a structure-based DART prediction approach.
• False-positives are very rare in the test and most false-negatives can be explained.

The ReProGlo assay was developed in 2009 to predict embryotoxic potential of drugs and chemicals by use of a stem cell-based in vitro system. It utilizes a luciferase reporter to detect drug-induced alterations in the canonical Wnt/β-catenin signaling pathway, which is involved in regulation of early embryonic development. It allows the simultaneous determination of cell viability and luciferase reporter activity in a high throughput format. The present study was conducted within the framework of the EU ChemScreen-project. It (1) enlarges the original number of test-compounds from 17 to now 80, (2) introduces a new classification scheme and (3) anchors the results against a prediction scheme based on structural features of chemicals. The assay is applicable as stand-alone for priority setting or in a test battery.