Sex Determination and Differentiation in Mammals

In most mammals, sex determination is initiated by transient expression of Sry, Sex-determining region Y gene, encoding an HMG-box transcription factor in bipotential gonadal supporting cells. In XY mouse gonads, SRY activates SOX9, another SRY-related HMG-box factor, during a critical time window (i.e. embryonic days 11.0–11.5) in male supporting cells. The maintenance of high-level SOX9 expression consequently induces Sertoli cell differentiation, leading to testis formation during the early organogenic stages. In XX gonads without Sry expression, bipotential supporting cells express FOXL2, a forkhead transcription factor, shortly after this time window, resulting in pre-granulosa cell differentiation and its subsequent contribution to ovarian folliculogenesis after birth. At later fetal stages, after cessation of SRY expression, the balance between masclinizing FGF9 and feminizing WNT4 signals affects the maintenance of high-level SOX9 expression in the supporting cells. During the perinatal and postnatal stages, each sex of the supporting cells is maintained by the balance between the masclinizing actions of SOX9 and DMRT1 and the feminizing actions of FOXL2, estrogen, and retinoic acid. In this chapter, we review recent knowledge regarding the SRY-dependent sex determination system during the critical time window and discuss the antagonistic interaction between testicular and ovarian factors during the late fetal, perinatal, and postnatal periods in mice.