Prenatal, but not postnatal exposure to chlorpyrifos affects social behavior of mice and the excitatory-inhibitory balance in a sex-dependent manner

The balance between excitatory and inhibitory neurotransmitters is essential for proper brain development. An imbalance between these two systems has been associated with neurodevelopmental disorders. On the other hand, literature also associates the massive use of pesticides with the increase of these disorders, with a particular focus on chlorpyrifos (CPF) a world-wide used organophosphate pesticide. This study was aimed at assessing social autistic-like behaviors on mice pre or postnatally exposed to CPF (0 or 1 mg/kg/day), in both sexes. In prenatal exposure, C57BL/6J pregnant mice were exposed to CPF through the diet, between gestational days (GD) 12 and 18, while a positive control group for some autistic behaviors was exposed to valproic acid (VPA) on GD 12 and 13. To assess postnatal exposure, C57BL/6J mice were orally exposed to the vehicle (corn oil) or CPF, from postnatal days (PND) 10–15. Social behavior and gene expression analysis were assessed on PND 45. Results showed social alterations only in males prenatally treated. GABA system was upregulated in CPF-treated females, whereas an increase in both systems was observed in both treated males. These findings suggest that males are more sensitive to prenatal CPF exposure, favoring the sex bias observed in ASD. •Social novelty preference was impaired in males' mice exposed prenatally to CPF or VPA.•Only prenatal exposure to CPF but not postnatal exposure alters social behavior.•Male mice prenatally exposed to CPF or VPA showed altered gene expression at both GABA and glutamate systems.•Toxic effects of prenatal CPF exposure involve different pathways depending on sex.