Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent impairment in social communication and social interaction. Recent studies revealed that environmental factors, especially the intrauterine developmental environment, played important roles in the development of ASD. It is hypothesized that maternal hyperandrogenism during pregnancy may increase the susceptibility of the fetus to ASD. In the present study, pregnant rats were treated with a low dose of letrozole (1 μg/kg/day) in an attempt to produce a hyperandrogenic intrauterine environment for the developing fetus. Results showed that rat pups prenatally exposed to hyperandrogenic intrauterine environment emitted less number of ultrasonic vocalizations when isolated from their dams and littermates. Additionally, the female rats in the treatment group spent less time in social interaction in adolescence and exhibited impaired heterosexual interaction in adult. Moreover, the duration of social interaction and heterosexual interaction of the female offspring were negatively correlated with maternal serum testosterone levels during pregnancy. These results suggest that prenatal exposure to hyperandrogenic intrauterine environment could induce autistic-like behavior in female rats and maternal hyperandrogenism during pregnancy should be considered as a potential risk factor for the etiology of ASD.