Using a multi-stage hESC model to characterize BDE-47 toxicity during neurogenesis

While the ramifications associated with polybrominated diphenyl ethers (PBDE) exposures during human pregnancy have yet to be determined, increasing evidence in humans and animal models suggests that these compounds cause neurodevelopmental toxicity. Human embryonic stem cell models (hESCs) can be used to study the effects of environmental chemicals on the successive stages of neuronal development. Here, using a hESC differentiation model, we investigated the effects of common PBDE congeners (BDE-47 or -99) on the successive stages of early neuronal development. First, we determined the points of vulnerability to PBDEs across four stages of in vitro neural development by using assays to assess for cytotoxicity. Differentiated neural progenitors were identified to be more sensitive to PBDEs than their less differentiated counterparts. In follow-up investigations, we observed BDE-47 to inhibit functional processes critical for neurogenesis (e.g., proliferation, migration) in hESC-derived ...