Suppressive effects of bisphenol a on the proliferation of neural progenitor cells

Endocrine disruptors (EDs) exert adverse effects on reproductive and immune function or neurological behavior. Bisphenol A (BPA), one of the environmental EDs, is widely used in the manufacture of plastics and epoxy resins. Studies reported that BPA affects reproductive organ growth and development. However, the potential adverse effects of BPA on neuronal development have not been fully explored. In this study, the potent harmful effects of BPA were investigated on the murine-derived multipotent neural progenitor cells (NPCs). Pretreatment of BPA significantly decreased proliferation of NPCs in a concentration-dependent manner. Moreover, at a high concentration (> 400 mu M), BPA was cytotoxic to NPCs. However, the low concentrations of BPA, previously shown to exert estrogenic actions, did not affect the proliferation of NPCs. BPA altered the activation of extracellular signal-regulated kinases and c-Jun-N-Kinases in a different manner without affecting activities of p38 kinases. It was also found that reactive oxygen species (ROS) were elevated in NPCs exposed to high concentrations of BPA, indicating oxidative stress-related cytotoxicity. These data show adverse effects of BPA on the nervous system and potentially on neonatal brain development.