Testis determination in mammals: more questions than answers

In humans, testis development depends on a regulated genetic hierarchy initiated by the Y-linked SRY gene. Failure of testicular determination results in the condition termed 46,XY gonadal dysgenesis (GD). Several components of the testis determining pathway have recently been identified though it h...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2001-06, Vol.179 (1), p.3-16
Main Authors: Veitia, Reiner A., Salas-Cortés, Laura, Ottolenghi, Chris, Pailhoux, Eric, Cotinot, Corinne, Fellous, Marc
Format: Article
Language:English
Subjects:
46,XY gonadal dysgenesis
46,XY sex reversal
Animals
DAX-1 Orphan Nuclear Receptor
Disorders of Sex Development
DNA-Binding Proteins - genetics
Female
Gene Deletion
Gene Dosage
Gene Duplication
Gonadal Dysgenesis, 46,XY - genetics
Life Sciences
Male
Mammals
Receptors, Retinoic Acid - genetics
Repressor Proteins
Sex determination
Sex Determination Processes
Testis - abnormalities
Testis - growth & development
Transcription Factors - genetics
XX sex reversal
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Summary:In humans, testis development depends on a regulated genetic hierarchy initiated by the Y-linked SRY gene. Failure of testicular determination results in the condition termed 46,XY gonadal dysgenesis (GD). Several components of the testis determining pathway have recently been identified though it has been difficult to articulate a cascade with the known elements of the system. It seems, however, that early gonadal development is the result of a network of interactions instead of the outcome of a linear cascade. Accumulating evidence shows that testis formation in man is sensitive to gene dosage. Haploinsufficiency of SF1, WT1 and SOX9 is responsible for 46,XY gonadal dysgenesis. Besides, data on SRY is consistent with possible dosage anomalies in certain cases of male to female sex reversal. 46,XY GD due to monosomy of distal 9p and 10q might also be associated with an insufficient gene dosage effect. Duplications of the locus DSS can lead to a failure of testicular development and a duplication of the region containing SOX9 has been implicated in XX sex reversal. Transgenic studies in mouse have shown, however, that this mammal is less sensitive to gene dosage than man. Here, we will try to put in place the known pieces of the jigsaw puzzle that is sex determination in mammals, as far as current knowledge obtained from man and animal models allows. We are certain that from this attempt more questions than answers will arise.
ISSN:0303-7207
1872-8057
0303-7207
DOI:10.1016/S0303-7207(01)00460-9