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Génétique moléculaire des dysgénésies testiculaires

Molecular genetic of testis dysgenesis

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La détermination testiculaire, première étape de la différenciation sexuelle masculine, est sous le contrôle de facteurs génétiques. Le rôle clé du gène SRY dans ces mécanismes est maintenant bien établi. Cependant de nombreux arguments, cliniques et génétiques, plaident en faveur de l’intervention d’autres gènes en aval ou en amont de SRY.

Ainsi, la plupart des hommes 46, XX ont hérité, par translocation, du gène SRY, responsable de la différenciation des gonades dans le sens testiculaire, mais dans 10% des cas le gène SRY n’est pas retrouvé. De même, si l’analyse de femmes 46, XY a participé à l’identification du gène SRY, 80% des cas de dysgénésies gonadiques ne sont pas expliqués par une anomalie de SRY.

Un certain nombre de situations cliniques permettent de suspecter le rôle des autosomes (chromosomes 1, 9, 10 17 …) et du chromosome X dans la pathologie de la détermination sexuelle. Les travaux les plus avancés concernent le facteur TDF-X, qui agirait comme un represseur de la détermination testiculaire.

Au total, les mécanismes moléculaires de la détermination sexuelle apparaissent extrêmement complexes, faisant intervenir probablement plusieurs gènes en une cascades de réactions.

Abstract

The first step of male differentiation is the testis determination which is genetically controled. The key role of SRY gene is now established. However, a number of clinical and genetic data favoured the role of other genes taking place upstream or downstream SRY.

Most of 46, XX males possess a translocated SRY gene and thus develop testis, but SRY gene is not found in 10% of such patients. Likewise, the molecular study of 46, XY females participated in the identification of SRY as testis determining factor, but 80% of XY gonadal dysgenesis are not explained by an abnormality of SRY gene.

Several clinical situations permitted to suspect the role of autosomal (chromosome 1, 9, 10 17 …) and X chromosome loci in the pathology of sex determination. Some recent works concern, in particular, the testis determining factor of the X chromosome (TDF-X) that could act as a repressor of the testis differentiation.

In conclusion, molecular mechanisms of sexual determination appear to be much complex, involving probably several genes in a pathway that remain to be elucidated.

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Correspondence to Ch. Sultan.

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Sultan, C., Lumbroso, S. & Lobaccaro, J.M. Génétique moléculaire des dysgénésies testiculaires. Androl. 4, 30–36 (1994) doi:10.1007/BF03034617

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Mots clés

  • Détermination sexuelle
  • SRY
  • mâles XX
  • dysgénésies testiculaires

Key words

  • sexual determination
  • SRY gene
  • XX males
  • testis dysgenesis