15.2.      Sex Determination in Humans

Chromosomal Sex Determination in humans

The chromosomal sex determination in human is further categorised into primary and secondary sex determination to make it easier. Primary sex determination is the term generally illustrates the chromosomal role in the determination of sex-specific gonads. Usually, in humans, the female is XX and the male is XY means the individuals of both sexes carries at least one X chromosome. Since the female is XX, each of her eggs has a single X chromosome. The male generates two types of gametes, either bearing the X chromosome or Y chromosome while the females bear only a single type of egg having X chromosome. When the egg receives another X chromosome from the sperm, the resulting individual is female or if the egg receives a Y chromosome from the sperm then the individual is male.

The mammalian Y chromosome is a crucial factor for sex determination; it carries a gene that encodes a factor that organizes the gonad into a testis rather than an ovary. For example, if an individual having a X chromosome and no second X or Y (i.e. XO)  then it will develop female gonads and if an individual carrying more than one X chromosomes with a single Y chromosome (i.e. XXXXXY) then it will develop male gonads.

The formation of ovaries and testes diverge from a common precursor (bipotential gonad) on the basis of Y chromosome. The sex-determining region, SRY gene of the Y chromosome causes the indifferent gonad to develop as a testis with the help of other genes found on the autosomes.

Secondary sex determination predicts the phenotypic characteristics of the body other than gonad. These characters include the specific assisted organs, glands, body size, voice pitch and musculature. These sex-specific characteristics are usually determined by gonadal hormones. However, the default female phenotype is generated even in the absence of both gonads.

The general cascade of mammalian sex determination is that the early embryo has two internal duct systems. One is Wolffian (male) and second is Müllerian (female), collectively known as bipotential gonad. But after 6 weeks a developmental pathway activates the different sets of genes that develop undifferentiated gonads as testis or ovaries and fix the gonadal sex of the embryo. The key elements in the mechanism of sex determination are described here

Sex-determining region of the Y chromosome (SRY) : 

It is the region of sex determination factors that resides on the short arm of the Y chromosome.  This region has a male-specific DNA sequence that encodes a peptide of 223 amino acids and acts as a transcription factor. This gene is termed as SRY (sex determining the region of the Y chromosome) that encodes the human testis determining factor.


It is an autosomal gene that plays a critical role in sex determination. When a human with XX chromosomes bears an extra copy of SOX9 then it will develop as males, even if they lack the SRY gene. Individuals with a single functional copy of sox9, have a disease with numerous skeletal and organ systems that are known as campomelic dysplasia and approximately its 75% XY patients develop as phenotypic females or hermaphrodites. Sox9 is found through all the vertebrates but the SRY doesn’t. So the Sox9 may be the older and more critical for sex determination, although in mammals it is activated by its relative, SRY gene.

Steroidogenic factor1 (SF1) :

It acts as the link between sry and the male developmental pathways. It is activated by SRY.  SF1 (steroidogenic factor1) is compulsory to develop bipotential gonad, but while Sf1 levels get down in the genital ridge it helps to the developing testis. It also appears to be active in masculinizing the Sertoli cells with Sox9 to elevate the levels of AMH transcription and also in the Leydig cells to activate the genes that encoding the enzymes to make testosterone.


It is a potential ovary-determining gene on the X chromosome, if an organism has two copies of DAX1 on an active X chromosome, the SRY signal would be reversed. It encodes a protein that competes with SRY factor and significant for the ovary development. It antagonises the function of SRY, and down-regulates SF1expression to assist the ovarian development.


It is a potential ovary-determining autosomal gene. Its expression becomes undetectable in XY gonads but maintained in XX.

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