Mammalian Sex Determination


Mammals, birds, reptiles, insects and even some corals all have two distinct forms – male and female. Cues for sexual development have undergone rapid evolution with some species relying on genetic cues and others on environmental. In mammals, sex development is governed by genetics and almost always involves heterogametic XY males and homogametic XX females. The Y chromosome contains a sex‐determining gene that initiates a cascade of developmental signals down the male path, leading to the development of testes and subsequently the male‐specific sex cords and genitalia. In the absence of the Y chromosome, development proceeds down the female path leading to ovaries and female genitalia. Mammalian sex determination involves a complex interplay of many genes, with antagonism between male and female pathways reinforcing fate. Despite the finely tuned process of sex determination, genetic aberrations can tip the balance, leading to sex reversal or intermediate sex development. Humans and mice with disruptions in key gonadal genes leading to atypical sex development have provided the majority of insights into the process of sex development, but much remains to be learned.

Key Concepts:

  • Mammals are sexually dimorphic.

  • Sex development has undergone rapid evolution.

  • Mammalian sex development is governed by complex genetic networks.

  • Study of humans and mice with atypical sex development have provided insights into the genetic pathways of sex development.

  • Massively parallel sequencing will accelerate future discoveries into the genetic basis of sex development.

Keywords: mammalian sex development; sex determination; disorders of sex development; gonadal development; gonadal dysfunction

Figure 1.

Overview of genes involved in the genetic cascade leading to development of the bipotential gonad and the subsequent development of either the testis or the ovary.



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Further Reading

Eggers S and Sinclair A (2012) Mammalian sex determination – insights from humans and mice. Chromosome Research 20(1): 215–238.

Marshall Graves JA (2008) Weird animal genomes and the evolution of vertebrate sex and sex chromosomes. Annual Review of Genetics 42: 565–586.

Ono M and Harley VR (2013) Disorders of sex development: new genes, new concepts. Nature Reviews Endocrinology 9(2): 79–91.

Quinn A and Koopman P (2012) The molecular genetics of sex determination and sex reversal in mammals. Seminars in Reproductive Medicine 30(5): 351–363.

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Tucker, Elena J, and Sinclair, Andrew H(Sep 2013) Mammalian Sex Determination. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024967]