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Aromatase et infertilité masculine

Aromatase and male infertility

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Chez la plupart des mammifères étudiés jusqu’à ce jour, l’aromatase est présente dans les cellules somatiques et les cellules germinales du testicule. Ainsi chez le rat adulte nous avons démontré l’existence d’une aromatase fonctionnelle, notamment dans les spermatocytes pachytènes et les spermatides rondes, qui assure une production d’estrogènes équivalente à celle des cellules de Leydig.

Chez l’homme, outre les cellules de Leydig nous avons mis en évidence l’aromatase dans les cellules sexuelles immatures et dans les spermatozoïdes éjaculés. Plus précisément, l’expression de l’aromatase diminue de 30% dans la fraction de spermatozoïdes immobiles comparée à celle contenant les spermatozoïdes mobiles d’un même prélèvement. Sur des échantillons issus de patients asthénospermiques, tératospermiques, et asthénotératospermiques, les taux de transcrits de l’aromatase sont respectivement diminués de 44, 52, et 67% par rapport à celui des patients normospermiques. De plus, ces taux de transcrits sont fortement corrélés (r = -0,64) aux pourcentage d’anomalies morphologiques du spermatozoïde et notamment à celles touchant la tête et l’acrosome en particulier.

Des techniques immunocytochimiques associées à la microscopie confocale indiquent une forte localisation de l’aromatase au niveau du flagelle et de la pièce intermédiaire. Les altérations de la fertilité chez l’homme déficient en aromatase et nos résultats suggèrent une participation probable des estrogènes dans la mobilité et la survie des spermatozoïdes. De plus, la corrélation du taux de transcrit au degré de tératospermie ainsi qu’une localisation partielle de l’aromatase au niveau de la tête du spermatozoïde semblent confirmer l’implication de l’aromatase au cours de la réaction acrosomique.

Il est donc envisageable d’utiliser l’aromatase comme marqueur du bon déroulement de la spermatogenèse et comme paramètre pour estimer la fécondance. En somme, dans le contrôle des fonctions de reproduction chez le mâle, outre les gonadotrophines et la testostérone, les estrogènes ont un rôle certainement plus complexe que cela avait été suggéré, compte tenu de l’expression particulière de l’aromatase et de la présence de récepteurs aux estrogènes dans les cellules testiculaires et les spermatozoïdes en particulier. L’infertilité est un problème de société qui concerne tous les pays et donc les études menées sur les empreintes nucléaires doivent permettre de mieux comprendre certains aspects de la Physiopathologie de la reproduction masculine.

Abstract

The mammalian testis is a complex organ which produces spermatozoa and synthesizes steroids. The transformation of androgens into estrogens is catalyzed by aromatase, an enzymatic complex encoded by a single copy-gene (cyp19) which contains 18 exons, 9 of which are translated. In man, in addition to Leydig cells, we have demonstrated the existence of a biologically active aromatase in immature germ cells and in ejaculated spermatozoa. The presence of estrogen receptors (ERa and ERβ) in immature germ cells and spermatozoa has also been reported.

A 30% decrease in the amount of aromatase mRNA is observed in immotile sperm compared to the motile sperm fraction from the same sample.

Aromatase and GAPDH transcript levels have also been determined by real-time PCR following RNA extraction in sperm samples from individual ejaculates of normozoospermic, and infertile patients. The aromatase protein and markers of either acrosome (CD 46), or tail (tubulin) or mid-piece (Mitotracker Green) or nucleus (DAPI) were immunolocalized by confocal microscopy.

In asthenoteratozoospermic, teratozoospermic and asthenozoospermic patients, aromatase gene expression is decreased by 67%, 52% and 44%, respectively, compared to normospermic controls. Statistical analysis between sperm morphology and aromatase/GAPDH ratio revealed a high degree of correlation (r=-0.64) between this ratio and the percentage of abnormal spermatozoa (especially microcephaly).

Using confocal microscopy, we have observed for the first time the existence of two sites for aromatase: the first site co-localized with tubulin is the tail with intensive staining in the mid-piece and the second site corresponds to the equatorial region of the head. Decreased sperm count and motility have been reported in genetically aromatase-deficient men.

In addition to gonadotrophins and testosterone, estrogens therefore also probably play a relevant role in spermatogenesis and human male gamete maturation. Our data suggest that aromatase transcripts could be a marker of male gamete quality and the existence of two sites of aromatase could be related to the role of estrogens in motility and acrosome reaction. Male infertility is a worldwide social problem and consequently, comparative studies of mRNA fingerprints in ejaculates between fertile and infertile men may contribute to elucidate some aspects of male reproductive pathology.

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Correspondence to Serge Carreau or Claire de Vienne or Lamia Said or Ali Saad or Isabelle Galeraud-Denis.

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Carreau, S., Vienne, C.d., Said, L. et al. Aromatase et infertilité masculine. Androl. 18, 258 (2008) doi:10.1007/BF03040719

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Mots clés

  • aromatase
  • estrogènes
  • spermatozoïde
  • testicule
  • homme
  • fertilité

Key words

  • aromatase
  • estrogens
  • spermatozoa
  • testis
  • man
  • fertility