Abstract
Autism spectrum disorders are characterized by impaired social and communicative skills and repetitive behaviors. Emerging evidence supported the hypothesis that these neurodevelopmental disorders may result from a combination of genetic susceptibility and exposure to environmental toxins in early developmental phases. This study assessed the effects of prenatal exposure to chlorpyrifos (CPF), a widely diffused organophosphate insecticide endowed with developmental neurotoxicity at sub-toxic doses, in the BTBR T+tf/J mouse strain, a validated model of idiopathic autism that displays several behavioral traits relevant to the autism spectrum. To this aim, pregnant BTBR mice were administered from gestational day 14 to 17 with either vehicle or CPF at a dose of 6 mg/kg/bw by oral gavages. Offspring of both sexes underwent assessment of early developmental milestones, including somatic growth, motor behavior and ultrasound vocalization. To evaluate the potential long-term effects of CPF, two different social behavior patterns typically altered in the BTBR strain (free social interaction with a same-sex companion in females, or interaction with a sexually receptive female in males) were also examined in the two sexes at adulthood. Our findings indicate significant effects of CPF on somatic growth and neonatal motor patterns. CPF treated pups showed reduced weight gain, delayed motor maturation (i.e., persistency of immature patterns such as pivoting at the expenses of coordinated locomotion) and a trend to enhanced ultrasound vocalization. At adulthood, CPF associated alterations were found in males only: the altered pattern of investigation of a sexual partner, previously described in BTBR mice, was enhanced in CPF males, and associated to increased ultrasonic vocalization rate. These findings strengthen the need of future studies to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders.
Highlights
Autism spectrum disorders (ASD) are characterized by marked reduction of social and communicative skills and presence of stereotyped movements associated with restricted interests
In this study we described several effects of the gestational CPF exposure in the BTBR mouse strain
Our findings highlight a specific vulnerability of BTBR mice to CPF as for early motor development, an effect not previously evidenced in other mouse strains
Summary
Autism spectrum disorders (ASD) are characterized by marked reduction of social and communicative skills and presence of stereotyped movements associated with restricted interests. Perinatal exposure to widespread environmental pollutants (i.e. heavy metals, organophosphate pesticides) appears to increase the risk of ASD but may not be sufficient per se to cause ASD [10,11,12,13]. If both genes and environment converge, a resulting dysfunction of neurotransmitters and signalling pathways could take place at key developmental time points [14]
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