Skip to main content
Download PDF
  • Article Original
  • Aromatase
  • Published:

Aromatase et infertilité masculine

Aromatase and male infertility

Andrologie volume 18, pages 258–263 (2008)Cite this article

Resume

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.

References

  1. AKINGBEMI B.T.: Estrogen regulation of testicular function. Reprod. Biol. Endocrinol., 2005, 3: 51.

    Article  PubMed  CAS  Google Scholar 

  2. AQUILA S., SISCI D., GENTILE M., MIDDEA E., SICILIANO L., ANDO S.: Human ejaculated spermatozoa contain active P450 aromatase. J. Clin. Endocrinol. Metab., 2002, 87: 3385–3390.

    Article  PubMed  CAS  Google Scholar 

  3. AQUILA S., SISCI D., GENTILE M. et al.: Towards a physiological role for cytochrome P450 aromatase in ejaculated human sperm. Hum. Reprod., 2003, 18: 1650–1659.

    Article  PubMed  CAS  Google Scholar 

  4. AQUILA S., SISCI D., GENTILE M. et al.: Estrogen receptor (ER)a and ERb are both expressed in human ejaculated spermatozoa: evidence for their direct interaction with phosphatidylinositol-3-OH Kinase/Akt pathway. J. Clin. Endocrinol. Metab., 2004, 89:1443–1451.

    Article  PubMed  CAS  Google Scholar 

  5. AQUILA S., MIDDEA E., CATALANO S. et al.: Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway. Hum. Reprod., 2007, 22: 2594–2605.

    Article  PubMed  CAS  Google Scholar 

  6. BECK K.J., HERSCEL S., HUNGERSHOFER R., SCHWINGER E.: The effect of steroid hormones on motility and selective migration of X-and Y-bearing human spermatozoa. Fertil. Steril., 1976, 27: 407–412.

    PubMed  CAS  Google Scholar 

  7. BRODIE A., INKSTER S., YUE W.: Aromatase expression in human male. Mol. Cell. Endocrinol., 2001, 178: 23–28.

    Article  PubMed  CAS  Google Scholar 

  8. CARPINO F., ROMEO F., RAGO F.V.: Aromatase immunolocalization in human ductuli efferentes and proximal ductus epididymis. J. Anat., 2004, 204: 217–220.

    Article  PubMed  CAS  Google Scholar 

  9. CARREAU S.: Paracrine control of human Leydig cell and Sertoli cell functions. Folia Histochem. Cytobiol., 1996, 3: 111–119.

    Google Scholar 

  10. CARREAU S., GENISSEL C., BILINSKA B., LEVALLET J.: The oestrogen sources in the testis and the reproductive tract of the male. Int. J. Androl., 1999, 22: 211- 223.

    Article  PubMed  CAS  Google Scholar 

  11. CARREAU S., LAMBARD S., DELALANDE C., GALERAUD-DENIS I., BILINSKA B., BOURGUIBA S.: Aromatase expression and role of estrogens in male gonad: a review. Reprod. Biol. Endocrinol., 2003, 1: 35.

    Article  PubMed  Google Scholar 

  12. CARREAU S., DELALANDE C., SILANDRE D., BOURGUIBA S., LAMBARD S.: Aromatase and estrogen receptors in male reproduction. Mol. Cell. Endocrinol., 2006, 246: 65–68.

    Article  PubMed  CAS  Google Scholar 

  13. CARREAU S., BOURGUIBA S., DELALANDE C. et al.: Estrogens and male reproduction. Immun. Endocr. Metab. Agents Med. Chem., 2008, 8: 59–65.

    Article  CAS  Google Scholar 

  14. CARREAU S., de VIENNE C., GALERAUD-DENIS I.: Aromatase and estrogens in man reproduction: a review and latest advances. Adv. Med. Sci., 2008, 53: sous presse.

  15. CHEN J.Q., YAGER J.D., RUSSO J.: Regulation of mitochondrial respiratory chain structure and function by estrogens/estrogen receptors and potential physiological/pathophysiological implications. Biochem. Biophys. Acta, 2005, 1746: 1–17.

    Article  PubMed  CAS  Google Scholar 

  16. DURKEE T.J., MUELLER M., ZINAMAN M.: Identification of estrogen receptor protein and messenger ribonucleic acid in human spermatozoa. Am. J. Obst. Gyn., 1998, 178: 1288–1295.

    Article  CAS  Google Scholar 

  17. FRASER L.R., BEYRET E., MILLIGAN S.R., ADEOYA-OSIGUWA S.A. Effects of estrogenic xenobiotics on human and mouse spermatozoa. Hum. Reprod., 2006, 21: 1184–1193.

    Article  PubMed  CAS  Google Scholar 

  18. GUNASEGARAM R., CHEW P.C.T., LOGANATH A., PEH K.L., RATMAN S.S.: A delta 4–3 keto pathway for testosterone synthesis in the human spermatozoa. Arch. Androl., 1995, 40: 49–57.

    Article  Google Scholar 

  19. HENDRY W.F., PARSLOW J.M., STEDRONSKA J.: Exploratory scrotomy in 168 azoospermic males. Brit. J. Urol., 1983, 55: 785–791.

    Article  PubMed  CAS  Google Scholar 

  20. IDAOMAR M., GUERIN J.F., LORNAGE J., CZYBA J.C.: Stimulation of motility and energy metabolism of spermatozoa from asthenospermic patients by 17b-estradiol. Arch. Androl., 1989, 22: 197–202.

    Article  PubMed  CAS  Google Scholar 

  21. LAMBARD S., GALERAUD-DENIS I., BOURAIMA H., BOURGUIBA S., CHOCAT A., CARREAU S.: Expression of aromatase in human ejaculated spermatozoa: a putative marker of motility. Mol. Hum. Reprod., 2003, 9: 117–124.

    Article  PubMed  CAS  Google Scholar 

  22. LAMBARD S., GALERAUD-DENIS I., SAUNDERS P.T.K., CARREAU S.: Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors. J. Mol. Endocrinol., 2004, 32: 279–289.

    Article  PubMed  CAS  Google Scholar 

  23. LAMBARD S., CARREAU S.: Aromatase and estrogens in human male germ cells. Int. J. Androl., 2005, 28: 254–259.

    Article  PubMed  CAS  Google Scholar 

  24. LAMBARD S., SILANDRE D., DELALANDE C., GALERAUD-DENIS I., BOURGUIBA S., CARREAU S.: Aromatase in testis: expression and role in male reproduction. J. Steroid. Biochem. Mol. Biol., 2005, 95: 63–69.

    Article  PubMed  CAS  Google Scholar 

  25. LEVALLET J., BILINSKA B., MITTRE H., GENISSEL C., FRESNEL J., CARREAU S.: Expression and immunolocalization of functional cytochrome P450 aromatase in mature rat testicular cells. Biol. Reprod., 1998, 58: 919–926.

    Article  PubMed  CAS  Google Scholar 

  26. LUCONI M., FRANCAVILLA F., PORAZZI I., MACEROLA B., FORTI G., BALDI I.: Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids, 2004, 69: 553–559.

    Article  PubMed  CAS  Google Scholar 

  27. O’DONNELL L., ROBERTSON K.M., JONES M.E., SIMPSON E.R.: Estrogen and spermatogenesis. Endocr. Rev., 2001, 22: 289–318.

    Article  PubMed  Google Scholar 

  28. OSTERMEIER G.C., GOODRICH R.J., DIAMOND M.P., DIX D.J., KRAWETZ S.A.: Toxard using stable spermatozoal RNAs for prognostic assesment of male factor fertility. Fertil. Steril., 2005, 83: 1687–1694.

    Article  PubMed  CAS  Google Scholar 

  29. PAYNE A.H., KELCH R.P., MUSICH S.S., HALPERN M.E.: Intratesticular site of aromatization in the human. J. Clin. Endocrinol. Metab., 1976, 42: 1081–1087.

    Article  PubMed  CAS  Google Scholar 

  30. PENTIKAINEN V., ERKKILA K., SUOMALAINEN L. et al.: Estradiol acts as a germ cell survival factor in the human testsi in vitro. J. Clin. Endocrinol. Metab., 2000, 85: 2057–2067.

    Article  PubMed  CAS  Google Scholar 

  31. PEREYRA-MARTINEZ A.C., ROSELLI C.E., STADELMAN H.L., RESKO J.A: Cytochrome P450 aromatase in testis and epididymis of malerhesus monkeys. Endocrine, 2001, 16: 15–19.

    Article  PubMed  CAS  Google Scholar 

  32. ROCHIRA V., GRANATA A.R.M., MADEO B., ZIRILLI L., ROSSI G., CARANI C. Estrogens in males: what we have learned in last 10 years ? Asian J. Androl., 2005, 7: 3–20.

    Article  PubMed  CAS  Google Scholar 

  33. RAGO V., BILINSKA B., PALMA A., ANDO S., CARPINO A.: Evidence of aromatase localization in cytoplasmic droplet of human immature ejaculated spermatozoa. Folia Histochem. Cytobiol., 2003, 41: 23–28.

    PubMed  CAS  Google Scholar 

  34. SEBASTIAN S., BULUN S.E.: A highly complex organization of the regulatory region of the human CYP19 (aromatase) gene revealed by the Human genome project. J. Clin. Endocrinol. Metab., 2001, 86: 4600–4602.

    Article  PubMed  CAS  Google Scholar 

  35. SIMPSON E.R., MAHENDROO M.S., MEANS G.D. et al.: Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr. Rev., 1994, 15: 342–355.

    PubMed  CAS  Google Scholar 

  36. SOLAKIDI S., PSARRA A.M.G., NIKOLAROPOULOS S., SEKERIS C.E.: Estrogen receptors alpha and beta (ERalpha and ERbeta) and androgen receptor (AR) in human sperm: localization of ERbeta and AR in mitochondria of the midpiece. Hum. Reprod., 2005, 20: 3481–3485.

    Article  PubMed  CAS  Google Scholar 

  37. TOPPARI J., LARSEN J.C., CHRISTIANSEN P. et al.: Male reproductive health and environmental xenoestrogens. Environm. Health Perspect., 1996, 104: 741–803.

    Article  CAS  Google Scholar 

  38. TURNER K.J., MACPHERSON S., MILLAR M.R. et al.: Development and validation of a new monoclonal antibody to mammalian aromatase. J. Endocrinol., 2002, 172: 21–30.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Université de Caen, EA2608, USC INRA, F-14000, Caen, France

    Serge Carreau, Lamia Said & Isabelle Galeraud-Denis

  2. Biologie de la Reproduction, CHRU, F-14000, Caen, France

    Claire de Vienne & Isabelle Galeraud-Denis

  3. Service de Cytogénétique et Biologie de la Reproduction, Hôpital F. Hached, Sousse, Tunisie

    Lamia Said & Ali Saad

Authors
  1. Serge Carreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire de Vienne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lamia Said
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ali Saad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isabelle Galeraud-Denis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Serge Carreau.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carreau, S., Vienne, C.d., Said, L. et al. Aromatase et infertilité masculine. Androl. 18, 258–263 (2008). https://doi.org/10.1007/BF03040719

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03040719

Mots clés

Key words

Basic and Clinical Andrology

ISSN: 2051-4190