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Sex bias in autism spectrum disorders: Examining how sexual differentiation leads to divergent neurodevelopment and social behaviour

Principal Investigator:
  • Ashlyn Swift-Gallant, Memorial University
  • Azrieli Foundation

Project Overview

Males are 4X more likely than females to develop Autism Spectrum Disorder (ASD), suggesting that the biology of sex development contributes to the risk of developing this neurodevelopmental condition. We will assess whether the Y chromosome and androgens—both of which contribute to male-typical development—underlie the greater risk for ASD among males. Using transgenic rodents, we will dissociate sex chromosomes (XX vs XY) from sex hormones (ovaries vs testes), generating chromosomal XX females with testes/male-typical sex hormones, and chromosomal XY males with ovaries/female-typical hormones. We will then assess risk of developing ASD in these animals to identify which aspects of sex development (sex chromosomes and/or sex hormones) contribute to the sex-bias of ASD. Next, we will assess whether increased sensitivity to androgens, via androgen receptors, in two primary cell types in the brain (i.e., neurons and the brain’s immune cells, microglia) elevates the risk of developing ASD among females and/or increases severity of ASD-like symptoms among males. Then, we will assess whether decreased sensitivity to androgens in neurons or microglia reduces risk of ASD among males and females. Through this work, we will gain an understanding of how sex development contributes to the sex bias of ASD in a rodent model, which we can then use to generate hypotheses for studies in humans. This fundamental knowledge is essential to the development of prevention and therapeutic strategies to best treat individuals at risk for sex-biased neurodevelopmental conditions, starting with ASD.