Sex Determination and Differentiation

In humans as well as other species, there are obvious differences between males and females. Differences such as the development of a penis or vagina, muscle mass, body size, the distribution of fat and the amount of distribution of body hair are all the differences that can be observed. These differences are a result of a long chain of events that begin during the early phases of embryology. It Involves Complex interactions between the environment and gene expression. Being male or female is determined in stages beginning at fertilization when the sex chromosomes carried by the sperms meet the egg. Females have XX chromosomes and Males have XY chromosomes. Having XX females and XY males provides a genetic framework for developmental events that eventually give us male or female appearance.  The formation of reproductive structures observed in males and females depend on several factors, these include; gene action and other genetic and hormonal interactions within the embryo (SRY Gene – an Overview | ScienceDirect Topics, 2019).

 Having XX and XY does not always mean that the individual is either male or female. The outcome depends on the distribution of genes on the X and Y chromosome. All eggs that are produced by females carry the X chromosomes, in males about half of the mature sperms carry the X chromosomes. An egg that is fertilised by a sperm that has the X chromosomes will have XX Zygote and will develop into a female (Cummings, 2009). Establishment of chromosomal sex happens at fertilization. However, even though this is the case, external genitalia are neither male nor female until about the third month of development.

Before this, the embryo has two undifferentiated gonads present, along with both sets of the male and female duct systems.  The second phase begins at 8 to 9 weeks when gene expression activates the different developmental pathway. This then causes the undifferentiated gonads to develop into testicles or ovaries. It is important to point out that there are alternative routes that produce an intermediate outcome in gonadal sex and sexual phenotype. For boys, the differentiation is not straightforward, If the Y chromosome is present, expressions of SRY gene on the Y chromosome will cause the undifferentiated gonads to become testis. A sex-determining gene that is found on the short arm of the Y chromosome called SRY activates the expression of other genes that play a part in the way testis develop. The SRY gene provides instruction for making protein called the sex determining region Y protein (SRY Gene – an Overview | ScienceDirect Topics, 2019). 

This protein is involved in male sex development and is usually determined   by the chromosomes in an individual. People usually have 46 chromosomes. The X and Y are called sex chromosomes because they help determine whether a person will develop male or female characteristics. The SRY gene is found on the Y chromosome. The sex determining region Y protein produced from this gene acts as a transcription factor. A transcription factor is a protein that binds to specific DNA sequence and contributes to the modulation of gene expression. Transcription factors are important determinants of epigenetic state of the cells. Many transcription factors have been identified and a huge proportion of the human genome appears to code for these proteins.  Once the testis development is initiated by the SRY gene, the testis then produces testosterone and Anti-Mullerian hormone. The formation of the internal male duct system that carries sperm is caused by testosterone’s effects on the Wolffian duct system (National Library of Medicine, 2020).  Females have two X chromosomes, so their sexual differentiation is not signalled by the SRY gene. The absence of these cues’ signals their sex organs to develop.

 Embryos with two X chromosomes and the absence of the Y chromosomes causes the gonads to develop into ovaries. Ovaries are developed when the cells in the outer layers of the gonads divide and push into the inner layers. The Wolffian duct system then disintegrates because the ovaries do not produce testosterone (Cummings, 2009). Hormones also shape the male and female appearance, after gonadal sex has been established the next phase in sex determination is the development of sexual appearance. In males, testosterone is converted into dihydrotestosterone, DHT directs the formation of external male features and influences brain development and size. Gonadal sex and sexual appearance are produced by separate pathways in males and females.

Clinical note

Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X chromosome and one Y chromosome in each cell, because their bodies are unable to respond to certain male sex hormones called androgens. Complete androgen insensitivity happens when the body cannot respond to androgen at all.  People with this condition have external sex characteristic of females, but do not have the uterus and therefore cannot menstruate. Affected Individuals have male internal sex organs that are undescended, which means that they are abnormally located in the pelvis and abdomen. Undescended testis’s have a small chance of becoming cancerous if they are not surgically removed.   Individuals with complete androgen insensitivity tend to have minimal or absent hair in the pubic or the under arms. The partial and mild forms of androgen insensitivity syndrome result when the bodies tissues are partially sensitive to the effects of the androgens. Individuals with partial androgen insensitivity can have genitalia that look female and genitalia that have both male and female characteristics (National Library of Medicine, 2020).

Congenital adrenal hyperplasia is a condition in which females have overactive adrenal glands. Adrenal glands are located over the kidneys, they are endocrine glands that are responsible for the production of several hormones.  There are two types of CAH, classic and non-classic, most children with this condition do not produce enough 21-hydroxylase, which is an enzyme that aids in the production of cortisol and aldosterone. Classic CAH is the more severe form and is usually noticed during infancy and early childhood (Yau et al., 2000). Congenital adrenal hyperplasia (CAH) causes the over production of a hormone called cortisol. Cortisol is a hormone that is structurally and functionally like testosterone. Cortisol plays a part in several functions, these include; control of sugar levels, regulation of metabolism, control of salt and water balance and helps control blood pressure. Females will develop musicalized genitalia to varying degrees, some females will an enlarged clitoris like penis formation. Others will have partially fused labia, similar to the scrotum (Sex Determination and Differentiation | SexInfo Online, 2019).  


Reference, G. H. (n.d.-a). Androgen insensitivity syndrome. Genetics Home Reference. Retrieved July 18, 2020, from

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Yau, M., Gujral, J., & New, M. I. (2000). Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment. In K. R. Feingold, B. Anawalt, A. Boyce, G. Chrousos, K. Dungan, A. Grossman, J. M. Hershman, G. Kaltsas, C. Koch, P. Kopp, M. Korbonits, R. McLachlan, J. E. Morley, M. New, L. Perreault, J. Purnell, R. Rebar, F. Singer, D. L. Trence, … D. P. Wilson (Eds.), Endotext., Inc.

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