Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain

For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain.

Automated summary

Neuroendocrinologists have long studied the role of gonadal hormones in sex differences in the brain, but it is only recently that the role of sex chromosomes has been explored. X and Y chromosomes encode different genetic information and are subject to different epigenetic regulations, contributing to sex differences between XX and XY individuals throughout life.