Abstract

Males and females exhibit numerous anatomical and physiological differences in the brain that often underlie important sex differences in physiology or behavior, including aspects relating to reproduction. Mammals’ sexual differentiation starts at conception when a fetus receives a couple of sex chromosomes. Until early weeks of gestation embryonal gonadal development is bi-potential according to genetic sex, embryonal gonads differentiate in testes or ovaries. Subsequently, hormonal products of the gonads induce male or female phenotype by early programming or organizational and then activational effects. Neural sex differences are both region-specific and trait-specific and may consist of divergences in synapse morphology, neuron size and number, and specific gene expression levels. In most cases, sex differences are induced by the sex steroid hormonal milieu during early perinatal development. The activating effects of ovarian hormones together with endocrine and exogenous influences enhance female characteristics at puberty and beyond determining phenotyping sex. A deeper understanding of these mechanisms will ultimately lead to our understanding of the molecular mechanisms underlying differences in the male and female brain, and importantly, differences in how the male and female brain may be able to respond to neuronal insults encountered with injury, neurodegeneration, normal aging, and pharmacological treatments.