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Génétique de l’infertilité chez l’homme, nouvelles approches

New approaches to the genetics of male infertility

Andrologie volume 13, pages 148–157 (2003)Cite this article

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15% des couples dans le monde ont des difficultés à se reproduire, à cause d’une infertilité. À ce jour, très peu de causes génétiques ont été associées à une infertilité de l’homme et la femme.

Jusqu’à présent, l’identification de mutations monogéniques causant une infertilité chez l’Homme est un domaine peu étudié et celles-ci sont probablement à l’origine d’un grand nombre d’infertilités dites idiopathiques et qu’il nous reste à décrypter.

En effet des modèles murins ont été créés depuis quelques années par invalidation de gène par recombinaison génétique: plus de 200 gènes ont ainsi été caractérisés responsables d’infertilité isolée ou syndromique, c’est le cas des gènes contrôlant la méiose.

Le déroulement de la méiose et des gènes associés a été largement caractérisé chez la levure. Récemment, des homologues de mammifères ont été clonés et invalidés chez la souris, montrant leurs rôles essentiels au cours de la méiose et pour la gamétogenèse. De plus, le phénotype gonadique de ces animaux mutants et celui de certains patients atteints d’infertilité inexpliquée est similaire. Une recherche d’éventuelles mutations dans des gènes de méiose, gènes hautement conservés au cours de l’évolution des espèces est en cours de réalisation.

Ces modèles murins sont d’une grande richesse pour étudier et disséquer les différentes étapes de la gamétogenèses normale et pathologique chez les mammifères.

Tous ces progrès faciliteront dans un avenir proche un diagnostic plus précis et donc un conseil génétique éclairé chez ces couples infertiles.

Abstract

15% of couples worldwide present with reproduction difficulties related to infertility. To date, very few genetic causes have been associated with male or female infertility.

The identification of single-gene mutations causing male infertility is not a field of intense research at the present time, although they are probably responsible for a large number of so-called idiopathic cases of infertility.

Murine models were created several years ago by gene knock-out by genetic recombination: more than 200 genes have been shown to be responsible for isolated syndromic infertility. This is the case for genes controlling meiosis.

The course of meiosis and the genes associated with this process have been largely characterized in yeasts. Mammalian homologues were recently cloned and knocked out in mice, demonstrating their essential roles during meiosis and gametogenesis. The gonadal phenotype of these mutant animals is similar to that of certain patients with unexplained infertility. The search for possible mutations in meiosis genes, genes that have been highly preserved during evolution, is currently underway.

These murine models are very useful to study and dissect the various steps of normal and pathological gametogenesis in mammals.

This progress should lead, in the near future, to more precise diagnosis and therefore informed genetic counselling in these infertile couples.

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Authors and Affiliations

  1. Human Genetics, Inserm 0021, Université Paris 7, Pavillon Baudeloque, Inserm U361, Hôpital Cochin, 123 Boulevard de Port-Royal, 75014, Paris

    Marc Fellous

  2. Service Histologie, Biologie de la Reproduction et Cytogénétique, Hôpital Tenon, Paris

    Jean-Pierre Siffroi

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  1. Marc Fellous
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Correspondence to Marc Fellous.

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Fellous, M., Siffroi, JP. Génétique de l’infertilité chez l’homme, nouvelles approches. Androl. 13, 148–157 (2003). https://doi.org/10.1007/BF03034429

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  • DOI: https://doi.org/10.1007/BF03034429

Mots clés

  • infertilité
  • causes génétiques
  • mutations monogéniques
  • gènes de méiose

Key-Words

  • infertility
  • genetic causes
  • single-gene mutations
  • meiosis genes

Basic and Clinical Andrology

ISSN: 2051-4190