Living Reference Work Entry

Endocrinology of the Testis and Male Reproduction

Part of the series Endocrinology pp 1-28

Date: Latest Version

Male Sexual Differentiation

  • Catherine H. SterlingAffiliated withDepartment of Anatomy and Neuroscience, The University of Melbourne
  • , Dagmar WilhelmAffiliated withDepartment of Anatomy and Neuroscience, The University of Melbourne
  • , Stefan Bagheri-FamAffiliated withDepartment of Anatomy and Neuroscience, The University of Melbourne Email author 


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.


Sex determination Testis Testis differentiation Transdifferentiation Genital ridge Gonad Testis cords Sertoli cells Peritubular myoid cells Germ cells Leydig cells Endothelial cells Sry Sox9 Fgf9 Dmrt1 Ovary Granulosa cells Estrogen signaling Foxl2