SRY, Sex Determination and Gonadal Differentiation


The commitment to develop into a male or female embryo is dependent on whether testes or ovaries develop from the primordial gonads. This decision is in turn controlled by the function of a gene, SRY, found on the Y chromosome in mammals. The proper expression and function of SRY in supporting cell precursors induces a cascade of gene expression that causes these cells to differentiate into Sertoli cells. Subsequently, Sertoli cells orchestrate the development of all other cell types resulting in the formation of testes, which produce hormones required for other aspects of male development. In the absence of SRY, or if SRY function is impaired, the supporting cells differentiate into granulosa cells, ovaries form and the embryo develops as a female.

Key Concepts:

  • Sex determination in mammals depends on the presence or absence of the Y‚Äźchromosome gene SRY.

  • SRY induces a program of gene expression in the sexually ambiguous primordial gonads of the embryo to induce differentiation of Sertoli cells.

  • Once Sertoli cells form, they influence other bipotential cell lineages to differentiate into cell types appropriate for a testis.

  • When SRY is absent or dysfunctional, a default genetic program instead causes granulosa cell differentiation and ovary development.

  • Mutations in genes involved in the testis and ovarian differentiation programs can cause human disorders of sex development.

Keywords: sex determination; SRY; sex reversal; Y chromosome; testis development; ovary development

Figure 1.

Sex reversal in humans caused by abnormal X–Y exchange. (a) Normal X–Y exchange. During male meiosis, the X and Y chromosomes align and genetically recombine (crossover; blue double‐headed arrow) within the pseudoautosomal or X–Y pairing region, shown in yellow. (b) Abnormal X–Y exchange, in which recombination occurs outside the X–Y pairing region, resulting in transfer of some Y chromosomal DNA to the X chromosome. The abnormal X chromosome thus generated is capable of directing male development, indicating that the testis‐determining locus TDF must reside close to the pseudoautosomal boundary on the human Y chromosome. Analysis of the 35 kb Y‐derived region present on an X chromosome in four XX males led to the identification of SRY, the Y‐linked testis‐determining gene.

Figure 2.

Structure of the early fetal testis. (a) Schematic diagram of a 13.5 dpc mouse testis showing development of testis cords. The testis is attached to a mesonephros, which contains the Wolffian duct that later develops to form the vas deferens. (b) The area demarcated by a rectangle in (a) is enlarged here, which shows the cell types that make up the testis cords (peritubular myoid cells that help maintain cord integrity and later provide the pulsatory contractions required for export of sperm; germ cells that later develop into sperm; and Sertoli cells whose processes intertwine and provide support and nourishment for the germ cells) and the interstitium between the cords (steroid‐producing Leydig cells and other cells such as macrophages and blood vessels). Sry is expressed in the precursors to the Sertoli cells, which then differentiate and signal to other immature cell types to regulate their differentiation and organisation.

Figure 3.

Cellular and molecular interactions during gonadal induction. Effector genes or gene products are shown in boxes and are described in the text. AMH, anti‐Müllerian hormone; DHT, dihydrotestosterone.



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Further Reading

Brennan J and Capel B (2004) One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nature Reviews Genetics 5: 509–521.

Koopman P (1999) Sry and Sox9: mammalian testis‐determining genes. Cellular and Molecular Life Sciences 55: 839–856.

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Wilhelm D and Koopman P (2006) The makings of maleness: towards an integrated view of male sexual development. Nature Reviews Genetics 7: 620–631.

Wilhelm D, Palmer S and Koopman P (2007) Sex determination and gonadal development in mammals. Physiological Reviews 87: 1–28.

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Koopman, Peter, and Wilhelm, Dagmar(Nov 2011) SRY, Sex Determination and Gonadal Differentiation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001144.pub3]