In the late 1980s, Peter Goodfellow in London, UK led a team of researchers who showed that the SRY gene in humans codes a protein that causes testes to develop in embryos. During this time, scientists in London and Paris, including Peter Koompan and John Gubbay, proposed that SRY was the gene on the Y chromosome responsible for encoding the testis-determining factor (TDF) protein. The TDF is a protein that initiates embryo to develop male characteristics. Looking for evidence that SRY was the TDF, Goodfellow and colleagues examined people who were anatomically female, but whose cells had Y chromosomes. Females normally have cells with two X sex chromosomes (XX), while males normally have cells with one X and one Y chromosome (XY). Goodfellow's team discovered that individuals with Y chromosomes developed as female instead of as male due to inactive SRY sequences on the Y chromosome. Goodfellow and colleagues compiled the results of their experiment in a paper titled Genetic Evidence Equating SRY and the Testis-Determining Factor in 1990. Their results showed that the SRY gene is necessary for male characteristics to develop in embryos, and that SRY encodes the TDF protein.

The Sex-determining Region Y (Sry in mammals but SRY in humans) is a gene found on Y chromosomes that leads to the development of male phenotypes, such as testes. The Sry gene, located on the short branch of the Y chromosome, initiates male embryonic development in the XY sex determination system. The Sry gene follows the central dogma of molecular biology; the DNA encoding the gene is transcribed into messenger RNA, which then produces a single Sry protein. The Sry protein is also called the testis-determining factor (TDF), a protein that initiates male development in humans, placental mammals, and marsupials. The Sry protein is a transcription factor that can bind to regions of testis-specific DNA, bending specific DNA and activating or enhancing its abilities to promote testis formation, marking the first step towards male, rather than female, development in the embryo.

Early 1990s research conducted by Peter Koopman, John Gubbay, Nigel Vivian, Peter Goodfellow, and Robin Lovell-Badge, showed that chromosomally female (XX) mice embryos can develop as male with the addition of a genetic fragment from the Y chromosome of male mice. The genetic fragment contained a segment of the mouse Sry gene, which is analogous to the human SRY gene. The researchers sought to identify Sry gene as the gene that produced the testis determining factor protein (Tdf protein in mice or TDF protein in humans), which initiates the formation of testis. Koopman's team published their results in 1991 in Male Development of Chromosomally Female Mice Transgenic for Sry gene. Their results showed that Sry gene partly determines the sex of an embryo and is the only gene on the Y chromosome necessary for initiation of male development in mice.

In humans, sex determination is the process that determines the biological sex of an offspring and, as a result, the sexual characteristics that they will develop. Humans typically develop as either male or female, primarily depending on the combination of sex chromosomes that they inherit from their parents. The human sex chromosomes, called X and Y, are structures in human cells made up of tightly bound deoxyribonucleic acid, or DNA, and proteins. Those are molecules that contain the instructions for the development and functioning of all life forms, including the development of physical traits and body parts that correspond with each biological sex. Humans who inherit two X chromosomes typically develop as females, while humans with one X and one Y chromosome typically develop as males. Sex determination is the beginning of the development of many characteristics that influence how a human looks and functions as well as the societal expectations that other humans have for each other.