The road to maleness: from testis to Wolffian duct

The establishment of the male internal reproductive system involves two crucial events: the formation of the testis and the maintenance and differentiation of the Wollffian duct. Testis formation, particularly the specification of Sertoli cell and Leydig cell lineages, is controlled strictly by genetic components initiated by the testis-determining gene SRY (sex-determining region of the Y chromosome). Conversely, Wolffian duct differentiation is not directly mediated via the composition of the sex chromosome or SRY, instead, it relies on androgens derived from the Leydig cells. Leydig cells do not express SRY, indicating that a crosstalk must be present between the SRY-positive Sertoli and Leydig cells to ensure normal androgen production. Recent advancement of genetic and genomic approaches has unveiled the molecular pathways for differentiation of Sertoli cells and Leydig cells as well as development of the Wolffian duct.