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Anomalies génétiques et infertilité masculine

Genetic analysis of human male infertility

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Résumé

Environ 15 % des couples sont confrontés à une infertilité. Dans la moitié des cas, la cause est masculine. Quatre-vingt-dix pour cent des causes d’infertilité chez l’homme ne sont toujours pas élucidées, certaines seraient dues à des causes génétiques ou environnementales ou les deux, impliquant alors des gènes de susceptibilité à caractériser. Les anomalies génétiques ont été recherchées par trois approches: 1) cytogénétique, surtout grace au progrès de la cytogénétique moléculaire et l’analyse directe des gamètes par la technique d’hybridation moléculaire in situ. La découverte d’une anomalie chromosomique, cause la plus fréquente des infertilités (y compris la délétion de l’Y), ne permet pas facilement de faire la distinction entre une anomalie génique impliquée dans le remaniement et une anomalie mécanique intrinsèque de la méiose; 2) l’analyse de gènes candidats utilise souvent les données obtenues dans les modèles animaux et principalement murins. Cette approche, très souvent utilisée dans la littérature, s’avère souvent longue, coûteuse et l’on découvre rarement une anomalie génique; c’est le cas par exemple des gènes de méiose; 3) l’approche mendélienne est évidemment l’approche de choix, en étudiant les cas familiaux d’infertilité qui sont plus fréquents que nous le pensons.

Abstract

Fifteen percent of couples are infertile and in about 50% of cases the cause is of male origin. The aetiology is still unknown in more than 90% of cases and there may be genetic or environmental causes. Three approaches are used to detect genetic causes for male infertility: 1) cytogenetics, resulting in particular from progress made in molecular cytogenetics and the direct analysis of gametes by in situ molecular hybridation techniques. When a chromosome anomaly, the most common cause of infertility, including deletion of the Y chromosome, is discovered, it is not easy to distinguish between gene anomalies resulting from change and mechanical anomalies that are an integral part of meiosis; 2) the analysis of candidate genes, which often uses data obtained from animal, usually murine, models. This approach, frequently described in the literature, tends to be lengthy, expensive and rarely results in the discovery of an abnormal gene, as is the case, for example, with meiotic genes; 3) Mendel’s approach is clearly the preferred choice, studying as it does cases of inherited infertility, which is much more widespread than we might think.

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Correspondence to M. Fellous.

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Vialard, F., Mandon-Pépin, B., Pellestor, F. et al. Anomalies génétiques et infertilité masculine. Basic Clin. Androl. 19, 2–16 (2009) doi:10.1007/s12610-008-0002-y

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Mots clés

  • Infertilité masculine
  • Chromosome Y
  • Cytogénétique
  • Famille avec infertilité

Keywords

  • Male infertility
  • Y chromosome
  • Cytogenetics
  • Infertile family