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The large numbers of environmental chemicals that now exist have made assessing their neurodevelopmental risks challenging. In this study, we quantified neurodevelopmental toxicity of bisphenol A, using a neurosphere assay in vitro. Neurosphere was isolated from rat E16 mesencephalone. A neurosphere assay was carried out in the amine-coated plates. Cells emerged from the neurosphere and migrated along the radial axis from the sphere. The migrating populations comprised cells that were positive for nestin, microtubule-associated proteins, and glial fibrillary acidic protein. Exposure to bisphenol A inhibited cell migration and decreased proliferative cells in dose- dependent manner. Quantitative analyses revealed a linear function between the inhibition of migration and the logarithm of bisphenol A concentration (0-100µM); the percent inhibition by 1µM bisphenol A of migration was 35% (p < 0.05). Thus, we showed for first time that bisphenol A inhibited migration as well as proliferation of neural stem cells in vitro and that a neurosphere assay in vitro is very useful to rapidly quantify neurodevelopmental toxicity of environmental chemicals.

Quantitative Analyses of Inhibitory Effects of Bisphenol A on Neural Stem-cell Migration Using a Neurosphere Assay in vitro