Brain Sexual Differentiation and Requirement of SRY: Why or Why Not?

Brain sexual differentiation is orchestrated by precise coordination of sex steroid hormones. In some species, programming of select male brain regions is dependent upon aromatization of testosterone to estrogen. In mammals, these hormones surge during the organizational and activational periods that occur during perinatal development and adulthood, respectively. In various fish and reptiles, incubation temperature during a critical embryonic period results in male or female sexual differentiation, but this can be overridden in males by early exposure to estrogenic chemicals. Testes development in mammals requires a Y chromosome and testis determining gene (in humans) (all other therian mammals), although there are notable exceptions. Two species of spiny rats: Amami spiny rat () and Tokunoshima spiny rat () and two species of mole voles (), lack a Y chromosome/ and possess an XO chromosome system in both sexes. Such rodent species, prototherians (monotremes, who also lack ), and fish and reptile species that demonstrate temperature sex determination (TSD) seemingly call into question the requirement of for brain sexual differentiation. This review will consider brain regions expressing / in humans and rodents, respectively, and potential roles of / in the brain will be discussed. The evidence from various taxa disputing the requirement of for brain sexual differentiation in mammals (therians and prototherians) and certain fish and reptilian species will be examined. A comparative approach to address this question may elucidate other genes, pathways, and epigenetic modifications stimulating brain sexual differentiation in vertebrate species, including humans.