Sex-dependent effects of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) on dendritic arborization of primary mouse neurons

Early life exposures to environmental contaminants are implicated in the pathogenesis of many neurodevelopmental disorders (NDDs). These disorders often display sex biases, but whether environmental neurotoxicants act in a sex-dependent manner to modify neurodevelopment is largely unknown. Since altered dendritic morphology is associated with many NDDs, we tested the hypothesis that male and female primary mouse neurons are differentially susceptible to the dendrite promoting activity of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95). Hippocampal and cortical neuron-glia co-cultures were exposed to vehicle (0.1% DMSO) or PCB 95 (100 fM - 1 μM) from day in vitro 7-9. As determined by Sholl analysis, PCB 95 enhanced dendritic growth in female but not male hippocampal and cortical neurons. In contrast, both male and female neurons responded to bicuculline with increased dendritic complexity. Detailed morphometric analyses confirmed that PCB 95 effects on the number and length of primary and non-...