Posts Tagged ‘X-linked’

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Human sex refers to the processes by which an individual becomes either a male or female during development. Complex mechanisms are responsible for male sex determination and differentiation. The steps of formation of the testes are dependent on a series of Y-linked, X-linked and autosomal genes actions and interactions. After formation of testes the gonads secrete hormones, which are essential for the formation of the male genitalia. Hormones are transcription regulators, which function by specific receptors. Ambiguous genitalia are result of disruption of genetic interaction. This review describes the mechanisms, which lead to differentiation of male sex and ways by which the determination and differentiation may be interrupted by naturally occurring mutations, causing different syndromes and diseases.


Sex determination: Initial event that determines whether the gonads will develop as testes or ovaries. Sex is determined by “the heat of the male partner during intercourse” –Aristotle (335 B.C.). Today: both environmental and internal mechanisms of sex determination can operate in different species.


Sex differentiation: Subsequent events that ultimately produce either the male or female sexual phenotype. Sexual differentiation is conformed in the human during four successive steps: the constitution of the genetic sex, the differentiation of the gonads, the differentiation of the internal and the external genital tractus and the differentiation of the brain and the hypothalamus.

Sex determination, which depends on the sex-chromosome complement of the embryo, is established by multiple molecular events that direct the development of germ cells, their migration to the urogenital ridge, and the formation of either a testis, in the presence of the Y chromosome (46, XY), or an ovary in the absence of the Y chromosome and the presence of a second X chromosome (46, XX). Sex determination sets the stage for sex differentiation, the sex-specific response of tissues to hormones produced by the gonads after they have differentiated in a male or female pattern. A number of genes have been discovered that contribute both early and late to the process of sex determination and differentiation. In many cases our knowledge has derived from studies of either spontaneous or engineered mouse mutations that cause phenotypes similar to those in humans. How mutations in these genes cause important clinical syndromes and the clinical entities that continue to elude classification at the molecular level have to be tested. Knowledge of the molecular basis of disorders of sex determination and differentiation pathways will continue to have a strong influence on the diagnosis and management of these conditions.

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