Behavioral effects of early-life exposure to perfluorooctanoic acid might synthetically link to multiple aspects of dopaminergic neuron development and dopamine functions in zebrafish larvae

• Perfluorooctanoic acid (PFOA) disrupts neural cell proliferation in zebrafish larvae. • Regulation of dopaminergic neuron development by multiple transcription factor was impaired by PFOA. • PFOA disrupts dopamine synthesis and reuptake in zebrafish larvae. • Modulation of dopaminergic neuron by mesencephalic astrocyte-derived neurotrophic factor (Manf) was impaired by PFOA. • Hypo-locomotor activity in zebrafish larvae induced by PFOA might synthetically link to multiple aspects of dopaminergic neuron development and dopamine functions in zebrafish larvae. Perfluorooctanoic acid (PFOA) is known as an environmental endocrine disruptor and has developmental neurotoxicity that could be associated with behavior changes in human and animal studies. Previous studies have shown that PFOA might affect the dopaminergic nervous system. However, the mode of action underlying the effects of PFOA remains poorly understood. Our study used zebrafish as an animal model to investigate the effects of early-life PFOA exposure on dopaminergic neuron development and dopamine functions in zebrafish larvae. Zebrafish fertilized eggs were exposed to different concentrations of PFOA (0, 10, 100, 1000 μg/L). After exposure to PFOA for 7 days, the locomotor activity of zebrafish was decreased; the mRNA levels of nuclear receptor subfamily 4 group a member 2b ( nr4a2b ), paired box 2 and 5 ( pax2, pax5 ), tyrosine hydroxylase 1/2 ( th1 / th2 ) and dopamine transporter ( dat ) were increased; mRNA and protein level of mesencephalic astrocyte-derived neurotrophic factor ( manf ) were decreased. Neural cell proliferation in the preoptic area of hypothalamus was increased. In conclusion, dopaminergic neuron development might be one of the targets of early-life PFOA exposure. The neurobehavior changes induced by PFOA exposure might link to multiple aspects of dopaminergic neuron development and dopamine functions in zebrafish larvae.