Throughout development, numerous biological events occur that differentially affect males and females. Specifically, sex-determining genes that are triggered by the sex-chromosome complement initiate a series of events that determine an organism's sex and lead to the differentiation of the body in sex-specific ways. Such events contribute to many unique sex differences, including the susceptibility to different diseases. Although it was believed that sex hormones singularly differentiated the brain and body, there is emerging research showing that genes also play a direct role. In this chapter, we review this line of work and focus on the use of a unique mouse model that separates the effect of gonadal hormones and sex chromosomes. As genetic technology continues to advance, our understanding of the role that hormones and genes play in sex differences can be used to advance the physical and mental health of both men and women.
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