Autism spectrum disorders (ASD) are characterized by reduced sociability, diminished communicative skills and repetitive behaviors. Notably, the proportion between boys and girls diagnosed with ASD is about 4:1 which suggests a higher susceptibility in boys to develop ASD. A striking difference between males and females in humans and other mammals is that males suffer a process of brain masculinization, due to the early exposure to gonadal hormones which, in turn, affect the organization of the brain. This developmental hallmark is essential for the adult animal to express the appropriate sexual behaviors in presence of a receptive female.
Our aim was to evaluate how the process of masculinization itself influences different behaviors relevant to ASD. To this aim, we studied sex differences and the effects of brain masculinization of female mice on different autism-relevant behaviors. We evaluated postnatal behavior, juvenile play and adult tests that evaluate sociability, repetitive behaviors, anxiety and depression. Finally, we performed the urine marking test and evaluated the oestrus cycle to assess the whether the protocol of neonatal exposure to estradiol resulted in brain masculinization and reproductive organs underdevelopment.
Our results show that the sex differences observed in exploration, repetitive behaviors and depression-related behaviors are largely reduced when females are neonatally treated with estradiol.