Arsenic exposure via drinking water during pregnancy and lactation induces autism-like behaviors in male offspring mice

Exposure to arsenic (As), an environmental toxicant, causes damages to the central nervous system (CNS) structure and function. Emerging epidemiological studies support that exposure to As, especially during the critical periods of the CNS development, may act as an environmental risk factor of autism spectrum disorders (ASD), which is characterized by behavioral changes, including abnormal social behaviors, restricted interests and repetitive behaviors. However, direct evidence supporting the cause-effect relationship between As exposure and the risk of ASD is still missing. Thus, we aimed to investigate whether As exposure during pregnancy and lactation led to autism-like behaviors in offspring mice in the present study. We established a mice model of Chemosphere (2022) exposure to As via drinking water during pregnancy and lactation and conducted a battery of behavioral tests to evaluate social behaviors, repetitive behaviors, anxiety behaviors and learning and memory ability in offspring mice. We found that perinatal exposure to As caused autism-like behaviors in male offspring, which demonstrated by abnormal social behaviors and repetitive behaviors. Anxiety-like behaviors, and learning and memory impairments, known as concomitant behavioral phenotypes in mice with autism-like behaviors, were also observed. Decreases of synaptic density, especially in cortex, hippocampus and cerebellum, are extensively observed in both ASD patients and animal models of ASD. Thus, immunofluorescence staining and western blotting were used to observe the expression of PSD-95 and SYP, well-known markers for presynaptic and postsynaptic membranes, to assess the synaptic density in offspring cortex, hippocampus and cerebellum. We found perinatal exposure to As decreased the expression of PSD-95 and SYP in these brain regions. This indicated that perinatal exposure to As caused decreases of synaptic density, a typical autism-like cellular alteration in brains, which may contribute to autism-like behaviors in offspring.

Automated summary

This study aimed to investigate whether exposure to arsenic during pregnancy and lactation leads to autism-like behaviors in offspring mice. The results showed that perinatal exposure to arsenic caused abnormal social behaviors and repetitive behaviors in male offspring mice, along with anxiety-like behaviors and learning and memory impairments. Immunofluorescence staining and western blotting revealed that perinatal exposure to arsenic resulted in decreases of synaptic density in the cortex, hippocampus, and cerebellum, which may contribute to the autism-like behaviors observed in offspring.