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.

Studies in Spermatogenesis is a two volume book written by Nettie Maria Stevens, and published by the Carnegie Institution of Washington in 1905 and 1906. In the books Stevens explains the research she conducted on chromosomal sex determination in the sperm and egg cells of insect species while at Bryn Mawr College, near Philadelphia, Pennsylvania. Studies in Spermatogenesis described early examples of chromosomal XY sex-determination.

The Y-chromosome is one of a pair of chromosomes that determine the genetic sex of individuals in mammals, some insects, and some plants. In the nineteenth and twentieth centuries, the development of new microscopic and molecular techniques, including DNA sequencing, enabled scientists to confirm the hypothesis that chromosomes determine the sex of developing organisms. In an adult organism, the genes on the Y-chromosome help produce the male gamete, the sperm cell. Beginning in the 1980s, many studies of human populations used the Y-chromosome gene sequences to trace paternal lineages. In mammals, the Y-chromosomes contain the master-switch gene for sex determination, called the sex-determining region Y, or the SRY gene in humans. In most normal cases, if a fertilized egg cell, called a zygote, has the SRY gene, the zygote develops into an embryos that has male sex traits. If the zygote lacks the SRY gene or if the SRY gene is defective, the zygote develops into an embryo that has female sex traits.

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.

Multiple theories about what determines sex were tested at the turn of the twentieth century. By experimenting on germ cells, cytologist Nettie Maria Stevens collected evidence to support the connection between heredity and the sex of offspring. Stevens was able to interpret her data to conclude that chromosomes have a role in sex determination during development. For her time, she was an emerging breed: a woman of science making the leap from the world of data collection to that of male-dominated interpretive work.