Estrogen Exposure in Early Development as a Factor in ASD Sex Bias

Autism has a well-established and prominent 4:1 male: female bias in diagnosis, but the biological basis for this difference remains unknown. One possible theory is that the presence of estrogen may play a role in the activity of brain cells that turn neurons on or off, which is part of the “excitation/inhibition” theory in autism. To test this theory, this fellow will create different types of neurons using induced pluripotent stem cells from both males and females with autism, with and without a rare genetic variation in an autism gene called neurexin. Then, estrogen will be applied to these cells and gene expression and functioning of different cell types will be compared. This gene-by-environment study will help identify the role of estrogen during development as a component in the later biological and behavioral features of females compared to males with autism.