Meeting Abstract
Fifteen percent of US children have neurodevelopmental disorders (NDDs), and incidences are increasing. Affected children, such as those with autism spectrum disorders (ASDs), often present atypical reciprocal social interactions that impair many important aspects of childhood development. NDDs arise from complex gene x environment interactions, and exposure to the correct hormonal milieu during specific developmental windows is critical for normal neuronal programming. Indeed, recent work indicates that several NDDs are associated with altered hormone concentrations during development, including ASDs and hyperactivity. One prominent hypothesis regarding the relationship between prenatal hormones and ASD is the extreme male brain theory, which suggests that excessive levels of prenatal androgens give rise to a hypermasculinized brain and autistic behavioral phenotype. Testosterone masculinizes the brain through binding to androgen receptor (AR) directly, or can be converted into one of two main metabolites: 5α dihydrotestosterone, which also binds AR, or estradiol, which binds estrogen receptor. To test the hypothesis that sex hormones influence neural organization underlying social behavior, we exposed pregnant Sprague-Dawley rats to dihydrotestosterone propionate, estradiol benzoate, or a vehicle on embryonic days 15.5-17.5 to target a critical window of sex-specific neurodevelopment. Offspring were assayed for a suite of behavioral tests used to indicate changes in social behavior (juvenile social play and social approach test), anxious behavior/hyperactivity (open field test), and spatial learning (Morris water maze). This work will take an important step toward understanding how hormone disruption during fetal development can lead to NDDs that are increasing in prevalence in our population.
