Humans generally have 23 pairs of chromosomes: 22 of them are known as autosomes, and the last pair is the sex chromosomes.
The X chromosome is essential for human life, so all humans have at least one. There are around 1,000 genes on this chromosome, which play major roles in reproduction and immunity (Graves et al., 2006).
The Y chromosome is about ⅓ the size of the X chromosome and has less than 200 genes, many of which are involved in the development of testes and the production of sperm (Graves et al., 2006). Portions of the Y chromosome can sometimes migrate to the X chromosome, which can lead to infertility in individuals with testes.
Most people have two sex chromosomes: two X chromosomes or one X and one Y. The most common alternatives are XXY, XYY, XXX, and single X (Blackless et al., 2000).
In some cases, individuals, who are considered intersex, may never know they have these chromosomal arrangements because there may not be any obvious signs.
Source: By National Human Genome Research Institute, http://www.genome.gov/Images/EdKit/bio1c_large.gif, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2132905
Most have probably heard of the SRY gene and its role in sex differentiation, but do you know about DAX1, SOX9, and Wnt4? We’ll be taking a look at each of these genes and the part they play in gonadal development. No one gene is the be-all and end-all of sex differentiation.
SRY
The SRY, or Sex-determining Region of the Y chromosome, gene is a major player in testes development. This gene becomes activated around week 7 of fetal development and continues to be expressed in adults (Hawkins, 1993; Ortenberg et al., 2002). It’s usually located on the Y chromosome but can migrate to the X chromosome, which can lead to the development of ovotestes or testes in XX individuals and the development of ovaries in XY individuals where this gene is missing. Mutations in this gene can also cancel out its function in individuals who have it (Gilbert, 2000). SRY isn’t the only gene important for gonadal development.
DAX1
DAX1 is located on the X chromosome and has often been characterized as an “anti-testes” or “sex reversal” gene. The role of DAX1 comes down to its dosage - how much of this gene someone has. In XY individuals, having two copies of DAX1 masks the function of SRY and promotes the development of ovaries rather than testes (Niakan & McCabe, 2005). However, not having any copies of DAX1 can also lead to ovary development (Meeks et al., 2003). DAX1 plays an important role in the development of both testes and ovaries by controlling the production of sex hormones in gonads and adrenal glands.
SOX9
SOX9, located on chromosome 17, has also been called a “sex reversal” gene for its role in testes development. This gene is activated by the SRY and DAX1 genes (Bouma et al., 2005) and is expressed in the early stages of testes development. The dosage of SOX9 is critical for its function: having two copies of this gene triggers testes development, even if there’s no SRY gene, and having no SOX9 copies can lead to ovary development (Croft et al., 2018; Jakob & Lovell-Badge, 2011).
Wnt4
Wnt4 is located on chromosome 1 and was originally thought to only be involved in ovary development. This gene is important also in the development of internal genitalia, especially the uterus and vagina, and the regulation of testosterone. However, much like DAX1, XY individuals who have either too much or too little Wnt4 won’t develop testes (partially or completely). XX individuals without Wnt4won’t develop testes or ovaries, but the blood vessels of their internal genitalia will mature in a way typically seen in the development of the testes and penis. Wnt4 is important for the development of the bipotential gonad (prior to the differentiation into testes, ovaries, or ovotestes) and then continues to play a major role in the development of ovaries, uterus, and vagina (Bernard & Harley, 2007; Jeays-Ward et al., 2004).
Bernard, P., & Harley, V. R. (2007). Wnt4 action in gonadal development and sex determination. The International Journal of Biochemistry & Cell Biology, 39(1), 31–43. https://doi.org/10.1016/j.biocel.2006.06.007
