Maternal DBP exposure promotes synaptic formation in offspring by activating astrocytes via the AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway

It has been demonstrated that activated astrocytes in the hypothalamus could disrupt GnRH secretion in offspring after maternal di-n-butyl phthalate (DBP) exposure, indicating that the effect of DBP on astrocyte activation and crosstalk between astrocytes and neurons is still worthy of further investigation. In this study, pregnant mice were intragastrically administered DBP dissolved in corn oil from gestational days (GD) 12.5-21.5. Maternal DBP exposure resulted in hippocampal astrocyte activation, abnormal synaptic formation, and reduced autonomic and exploratory behavior in offspring on postnatal day (PND) 22. Further studies identified that mono-n-butyl phthalate (MBP) induced astrocyte activation and proliferation by activating the AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway. Moreover, upregulated thrombospondin 1 (TSP1) in activated astrocytes regulated synaptic-related protein expression. This study highlights the neurotoxicity of maternal DBP exposure to offspring, which provides new insights into identifying potential molecular targets for the treatment of diseases related to neurological development disorders in children.