Exposure To Elevated Prenatal Testosterone Metabolites Induce Autism-Like Behavior In Rats : Evidence For The Extreme Male Brain And Implications For Human Health

Abstract

Neurodevelopmental disorders such as autism spectrum disorder (ASD) originate during early brain development and are the result of complex interactions between genetic and environmental factors. Disruptions in the prenatal hormone environment have been associated with increasing the risk for autism. The extreme male brain theory of autism states that ASD results from abnormally high levels of prenatal testosterone that result in a hypermasculinized (autistic) brain. Prenatal androgen signaling programs behavior through the actions of androgen or estrogen receptors throughout diverse brain regions. The balance of this sex hormone signaling is critical for neuronal organization, and disruptions in normal prenatal hormone levels lead to aberrations in critical behaviors such as juvenile social play, which is important for normal cognitive and social development. This research demonstrates that exposure to excess testosterone metabolites during development induces autism-like behaviors in the rat, including reduced social interactions, abnormal stress response, and enhanced spatial ability, which support the extreme male brain theory.