Prenatal Di-methoxyethyl phthalate exposure impairs cortical neurogenesis and synaptic activity in the mice

Di-methoxyethyl phthalate (DMEP) is a well-known environmentally prevalent endocrine disruptor and may be associated with neurodevelopmental disorders including attention deficit/hyperactivity disorder and intellectual disability. However, the regulatory mechanisms leading to these neurodevelopmental disorders are still poorly understood. Here, we demonstrate that prenatal DMEP exposure causes abnormal brain morphology and function in the mice. DMEP (50 mg/kg) was chronically administered to pregnant mice orally once a day starting on embryonic day 0 (E0) to breast-feeding cessation for the fetus. We found that prenatal DMEP exposure significantly reduced the number of neurons in the parietal cortex by impairing neurogenesis and gliogenesis during the developing cortex. Moreover, we found that prenatal DMEP exposure impaired dendritic spine architectures and synaptic activity in the parietal cortex. Finally, prenatal DMEP exposure in mice induces hyperactivity and reduces anxiety behaviors. Altogether, our study demonstrates that prenatal DMEP exposure leads to abnormal behaviors via impairment of neurogenesis and synaptic activity. Prenatal DMEP exposure can lead to abnormal neurogenesis and astrogenesis in brain development.Prenatal DMEP exposure changes the gene expression profile during cortical development.Prenatal DMEP exposure leads to synaptic dysfunction in the cerebral cortex by affecting dendritic spine and synaptic formations.Prenatal DMEP exposure results in abnormal behaviors.image