Sex chromosome genes directly affect brain sexual differentiation.

Sex differences in the brain are caused by differences in gonadal secretions: higher levels of testosterone during fetal and neonatal life cause the male brain to develop differently than the female brain. In contrast, genes encoded on the sex chromosomes are not thought to contribute directly to sex differences in brain development, even though male (XY) cells express Y-chromosome genes that are not present in female (XX) cells, and XX cells may have a higher dose of some X-chromosome genes. Using mice in which the genetic sex of the brain (XX versus XY) was independent of gonadal phenotype (testes versus ovaries), we found that XY and XX brain cells differed in phenotype, indicating that a brain cell's complement of sex chromosomes may contribute to its sexual differentiation.