Male Sexual Differentiation

Abstract

In mammals, the bipotential genital ridges develop into the testes or ovaries depending on the presence or absence of the Y chromosome. The genital ridges contain three main types of bipotential precursor cells: supporting cells, which in the developing testis differentiate into Sertoli cells, steroidogenic cells giving rise to Leydig cells, and primordial germ cells developing into sperm. Each of these cell types play a critical role in the development and function of adult testes. Expression of the sex-determining region Y gene (Sry) in the supporting cells of the undifferentiated genital ridges initiates a molecular cascade leading to testis differentiation. During this process, carefully orchestrated genetic and physical interactions within and among the cell types residing in the developing testis lead to compartmentalization into two distinct regions, the testis cords and the interstitial space, and ultimately to the full development of the testis. Intriguingly, once determined, gonadal sex and therefore the male or female phenotype must be maintained through active repression of the molecular pathways determining the opposite sex. In this chapter, we will discuss the genetic and cellular mechanisms driving the development of a testis as well as the molecular pathways involved in maintaining gonadal sex.