Sex determination varies greatly among animal species including mammals. Although two identical (XX) or distinct (XY) gonosomes are found in all species of the latter, the ratio of sex-specific content varies considerably ranging from a small minority in monotremes to more than 90% in primates. However, the similarities are strong enough to allow us to study those mechanisms in comparison with each other and obtain useful information on the evolution of sex determination. The paper focuses on the basic principles of sex determination in mammals, stressing the common evolutionary background behind the striking similarities observed even among phenotypically and geographically distinct species. Sequencing and comparative genetic data seem to suggest that a common evolutionary origin for all mammalian sex determination strategies is most probable. Nevertheless, original research data is still required for the understanding of the complex underlying mechanisms

In mammals, sex determination is based on the presence of two identical (XX) or distinct (XY) gonosomes. This is believed to be the result of a lengthy evolutionary process emerging from a common ancestral autosomal pair. Indeed, X and Y present different levels of homology in various mammals, supporting the argument of a gradual structural differentiation starting around the Sex-determining Region Y (SRY) region. The latter initiates a gene cascade that results in the formation of a male. Regulation of sex steroid production is also a major result of these genetic interactions. Similar observations have been described not only in mammals, but also in other vertebrates, emphasizing the need for further study of both normal hormonal regulators of sexual phenotype and patterns of epigenetic/environmental disruption.

The paper focuses on the basic principles of sex determination in mammals, stressing the common evolutionary background behind the striking similarities observed even among phenotypically and geographically distinct species. There are major potential implications of the genetic regulation of sex determination, with particular reference to human reproductive health and disease. However, this connection needs to be further explored, as further research could reveal more details on the origin and development of the mammalian sex chromosomes (i.e., gonosomes) and the exact role of their components in sex determination and differentiation.

Sex Determination from an Evolutionary Perspective: The Mammalian Regulatory Model, gonosomes, phenotypically and geographically, genetic regulation, Sex-determining Region, hormonal regulators, epigenetic, sex steroid production, chromosome aneuploidies, marsupials, mammary glands and scrotum.