Sex Determination

Abstract

In mammals, the decision to become male or female is initiated in the gonad by the sex determination pathway, which drives and instructs the differentiation of the gonad into a testis or ovary. The gonad develops as an undifferentiated primordium that is initially indistinguishable between XX (female) and XY (male) embryos; the gonad is a uniquely bipotential organ in its ability to give rise to a testis or ovary. Prior to sex determination, the establishment of the gonadal anlage (i.e., the setup of genetic and cellular programs promoting its identity) by a set of specification factors is critical. The master switch of mammalian sex determination, the Sry gene on the Y chromosome, is the genetic trigger that sets sex determination in motion and launches the testis program in the gonad. Sry is necessary and sufficient for male development, while the ovarian pathway (under the control of a female-specific program) ensues in the absence of Sry expression during a critical developmental time window. In this chapter, we will cover the processes of gonad specification and sex determination, focusing on major factors and signaling pathways involved in the male-versus-female decision and the establishment of sexual dimorphism in the gonad. Additionally, we will briefly discuss evolutionarily conserved aspects of chromosomal sex determination mechanisms and environmental influences that potentially impact sex determination and sex ratio in mammals.