A component of human biological development is a gene located on the Y chromosome known as the Sex-determining Region Y, or SRY. This gene is involved in the processes that direct how an individual develops based on their chromosomes. Humans have 46 chromosomes in each cell, two of which are designated as sex chromosomes, X and Y. Individuals with one X and one Y chromosome are male, while those with two X chromosomes are female. The SRY gene’s presence on the Y chromosome initiates a specific developmental sequence.
The Primary Function of the SRY Gene
During early embryonic development, the internal reproductive structures are undifferentiated, meaning they have the potential to develop along either male or female pathways. Around the sixth week of gestation in an XY embryo, the SRY gene becomes active. Its primary function is to produce a protein called the Testis-Determining Factor (TDF), also known as the sex-determining region Y protein. This protein is a transcription factor, a specific type of protein that can bind to DNA.
The TDF protein attaches to particular segments of DNA, which in turn helps to regulate the activity of other genes. By binding to DNA, the TDF protein dramatically alters its shape, which influences how other genes are expressed. This action initiates a cascade of genetic events that directs the undifferentiated gonads to begin developing into testes.
The SRY gene’s role is centered on this single event of testis formation. It acts as the “master switch” that starts the process of male development. The expression of this gene is the definitive step that separates the developmental pathways of the gonads in XY and XX embryos.
The Developmental Cascade After SRY Activation
Once the SRY gene has directed the undifferentiated gonads to become testes, these newly formed organs begin to produce hormones that continue the process of male development. The testes secrete two significant hormones: testosterone and Anti-Müllerian Hormone (AMH). Each of these hormones has a distinct and separate function in shaping the internal reproductive anatomy.
Testosterone is responsible for promoting the development of the Wolffian ducts, which are primitive tubes present in the early embryo. Under the influence of testosterone, these ducts differentiate into the male internal reproductive organs, including the epididymis, vas deferens, and seminal vesicles.
Simultaneously, the testes produce AMH. The role of AMH is to cause the degradation of a different set of embryonic tubes called the Müllerian ducts. In the absence of AMH, these ducts would develop into the female internal reproductive organs. By causing the Müllerian ducts to break down, AMH prevents the formation of a uterus and fallopian tubes.
Development in the Absence of SRY
In an embryo that does not have a Y chromosome, and therefore lacks the SRY gene, the developmental pathway proceeds differently. Without the SRY gene, the Testis-Determining Factor protein is not produced. This absence of a signal from SRY means the undifferentiated gonads will naturally develop into ovaries.
Once the ovaries form, the subsequent development of internal reproductive structures is guided by the absence of the hormones produced by the testes. Without testosterone, the Wolffian ducts, which would otherwise form male organs, fail to develop and eventually degrade.
Because there are no testes, there is no production of Anti-Müllerian Hormone (AMH). In the absence of AMH, the Müllerian ducts are not inhibited and are free to develop. These ducts differentiate into the female internal reproductive organs, including the fallopian tubes, uterus, and the upper portion of the vagina.
Variations in SRY and Sex Development
On occasion, events during the formation of sperm can lead to variations in the distribution of the SRY gene, resulting in conditions that affect sex development.
One such variation is known as 46,XX testicular difference of sex development, sometimes referred to as de la Chapelle syndrome. This can occur when the SRY gene is accidentally moved from the Y chromosome to an X chromosome during meiosis. If a sperm carrying an X chromosome with a translocated SRY gene fertilizes an egg, the resulting embryo will have an XX karyotype but will also have the SRY gene. The presence of the SRY gene can lead to the development of male characteristics.
Conversely, a condition known as 46,XY complete gonadal dysgenesis, or Swyer syndrome, can arise if the SRY gene on the Y chromosome is missing or contains a mutation that renders it non-functional. An individual with an XY karyotype but a non-functional SRY gene will not produce the Testis-Determining Factor. Consequently, the gonads do not develop into testes, and the default pathway of female development ensues.