Male Sex Determination: Genetics


The basic dichotomy of life is sexual. Sex is important not only for reproductive role but also for physical attributes, personal identity and disease susceptibility. The determination of sex, that is, whether one is male or female, is controlled genetically. The key genetic event in male sex determination is transmission of a Y chromosome from father to offspring. In the developing gonad, the sex‚Äźdetermining gene on this chromosome, SRY, triggers the expression of a repertoire of other genes. These genes cause the gonad to develop as a testis. Hormones secreted by the developing testis influence the differentiation of male internal and external genitalia and other somatic features.

Key Concepts

  • Testes are important not only for mediating male reproduction but also for producing hormones that masculinise other organs, including internal and external genitalia.
  • Male and female embryos share a common gonadal ridge that has the potential to differentiate either as a testis or as an ovary.
  • The SRY gene acts as the master switch for testis differentiation.
  • Once a testis has developed, the DRMT1 gene acts to prevent the testis from transdifferentiating into an ovary.
  • The other reproductive organs are derived from a common set of internal and external genital structures.
  • The differentiation of the prostate, seminal vesicles and epididymis from the Wolffian ducts is mediated by the hormone testosterone.
  • The formation of the penis and scrotum is mediated by the hormone dihydrotestosterone.
  • Disorders of sex development (DSDs) arise when mutated genes prevent the normal gonadal and genital development.
  • Germ cell tumours are common among individuals with 46,XY DSDs.
  • Individuals who develop testicular cancer may have a mild form of DSDs.

Keywords: sex development; sexual differentiation; testis; gonad; Y chromosome; disorder of sex development

Figure 1. Organisation of the specialised cells that comprise the seminiferous tubules of the human testis.
Figure 2. Structure of the human embryo at 40–50 days of gestation, highlighting the gonadal ridge and the migration of the germ cells from the yolk sac via the hindgut.
Figure 3. Development of the human internal genitalia from the Wolffian and Müllerian ducts.
Figure 4. Development of the human external genitalia from the genital tubercle and labioscrotal folds and swellings.


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Further Reading

Arboleda VA, Sandberg DE and Vilain E (2014) DSDs: genetics, underlying pathologies and psychosexual differentiation. Nature Reviews Endocrinology 10: 603–615.

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Ostrer H (2014) Disorders of sex development (DSDs): an update. Journal of Clinical Endocrinology & Metabolism 99: 1503–1509.

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Ostrer, Harry(Sep 2017) Male Sex Determination: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006235.pub2]