Bisphenol A affects axonal growth, musculature and motor behavior in developing zebrafish

Bisphenol A (BPA) is a ubiquitous contaminant in environment and human body. The reproductive and developmental effects of BPA exposure in aquatic and laboratory animals have been extensively studied. However, BPA exposure on the nervous system and motor behavior development are not well understood. In this study, we utilized zebrafish embryo as a model system to investigate the effect of developmental BPA exposure on larval teratology, motor behaviors, axonal growth of spinal motoneurons and muscle structure at various developmental stages. Our findings revealed that BPA exposure altered spontaneous movement, significantly decreased touch response and swimming speed in response to light stimulation in developing zebrafish. These effects were observed at the concentrations that did not yield any significant teratogenic effects. Correlated with those changes in swimming activity, BPA-induced axial muscle damage occurred at the same concentration range (1-15 μM), but disruption of axonal growth of primary and secondary motoneuron occurred only at higher concentration (15 μM). BPA-induced apoptotic cell death subsequent to initial ROS formation and oxidative DNA damage may be the underlying mechanism for axial muscle damage, suggesting the functional relevance of muscle structural changes and the observed deficits in swimming activity.