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Estrogènes et spermatozoïdes

Estrogens and spermatozoa

Resume

Les estrogènes sont depuis longtemps considérés comme des hormones sexuelles typiquement femelles; cependant ils semblent jouer un rôle éminent dans le testicule tout aussi important que leur fonction endocrine classique. L’aromatase (enzyme qui transforme irréversiblement les androgènes en estrogénes) est impliquée notamment dans le développement, la différenciation sexuelle et le comportement, la reproduction, les métabolismes osseux et lipidique, le fonctionnement du cerveau; son importance est donc capitale chez I’homme. Les données mettant en évidence au sein du testicule plusieurs types cellulaires opérationnels dans la production d’estrogènes, associés à la présence de récepteurs spécifiques (ERα et ERβ) à plusieurs niveaux du tractus génital mais aussi sur certaines cellules sexuelles, plaident donc fortement en faveur d’un rôle intrinsèque de ces hormones femelles en dehors de leur impact connu sur la secrétion gonadotrope. Un certain nombre de preuves et d’arguments permettent de penser qu’une (ou des) relation (s) existe (nt) entre estrogènes et infertilité, en particulier au niveau épididymaire où la composition du fluide luminal de la tête de l’épididyme (zone essentielle pour la maturation du spermatozoïde) serait modulée par ces hormones femelles. Chez I’homme, les sites de production et le rôle des estrogènes dans la spermatogenèse et la spermiogenèse ne sont pas encore totalement élucidés; cependant, dans l’étude des mécanismes physiopathologiques impliqués dans l’infertilité la participation des estrogènes est de plus en plus envisagée. En conséquence, les estrogènes se révèlent donc être essentiels pour la reproduction du mâle ce qui nous amènent à reconsidérer certaines notions de la physiologie de la reproduction masculine, avec non seulement des régulations androgéno-dépendantes mais aussi estrogéno-contrôlées.

Abstract

Aromatase is the terminal enzyme responsible for estrogen biosynthesis; it is present in the endoplasmic reticulum membrane of steroidogenic cells in vertebrates. This enzyme functions with the ubiquitous reductase as the electron donor. The aromatase gene is unique and its expression is regulated in a tissue and more precisely in a cell-specific fashion via the alternative use of several promoters located in the first exons.

This enzymatic complex is generally involved in development, reproduction, sexual differentiation and behaviour, but also in bone and lipid metabolism, brain functions and diseases such as breast and testicular tumors. The aromatase gene expression and its transduction in a fully active protein in testicular somatic cells and germ cells together with the widespread distribution of estrogen receptors (ERα & β) in the testis and the genital tract of the male, are clearly in favor of a physiological role for estrogens in the spermatogenesis processings especialy in sperm maturation. Therefore, we begin to understand the physiopathological roles of the estrogens in males indeed, the aromatase deficiency is associated, with severe bone maturation problems and sterility in man. Conversely, it is also obvious that estrogens in excess are responsible of the impaired spermatogenesis. These female hormones (or the ratio androgens/estrogens) do play a physiological role in the development and maintenance of male gonadal functions and obviously, several steps are concerned especially the sperm production and maturation.

References

  1. 1.

    ARAI Y., MORI T., SUZUKI Y., BERN H.A. Longterm effects of perinatal exposure to sex steroids and diethylstilbestrol on the reproductive system of male mammals. Int. Rev. Cytol., 1983; 84: 235–268.

  2. 2.

    AUGER J., KUNSTMANN J.M., CZYGLIK F., JOUANNET P. Decline in semen quality among fertile men in Paris during the past 20 years. N. Engl. J. med., 1995; 332: 281–285.

  3. 3.

    BECK K.J., HERSCHEL 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.

  4. 4.

    BELMONTE S., MATURANO M., BERTINI F., PUSIOL E., SARTOR T., SOSA A. Changes in the content of rat epididymal fluid induced by prolonged treatment by tamoxifen. Andrologia, 1998; 30: 345–350.

  5. 5.

    BERGH J.P. Oestrogens-essential for reproduction in males, too. Eur. J. Endocrinol., 1998, 138: 497–498.

  6. 6.

    BULUN S.E. Aromatase deficiency in women and men: would you have predicted the phenotypes? J. Clin. Endocrinol. Metab., 1996; 81: 867–71.

  7. 7.

    BULUN S.E., NOBLE L.S., TAKAYAMA K. et al. Endocrine disorders associated with inappropriated high aromatase expression. J. Steroid. Biochem. Molec. Biol., 1997; 61: 133–139.

  8. 8.

    CARANI C., QIN K., SIMONI M., et al. Effect of testosterone and estradiol in a man with aromatase deficiency. N. Engl. J. Med., 1997; 337: 91–95.

  9. 9.

    CARREAU S. Germ cells-Sertoli cells interactions and Leydig cell function. In: Dufau M. L., Fabbri A., Isidori A., eds. Cell and Molecular Biology of the testis. Frontiers in Endocrinology 1994; 5: 137–48.

  10. 10.

    CARREAU S. Paracrine control of human Leydig cell and Sertoli cell functions. Folia Histochem. Cytobiol. 1996; 34: 111–9.

  11. 11.

    CARREAU S., LEVALLET J. L’aromatase testiculaire: du gène à la protéine. Andrologie, 1998; 8: 191–198.

  12. 12.

    CARREAU S., BILINSKA B., LEVALLET J. Les cellules germinales mâles: une source nouvelle d’estrogènes dans le testicule des mammifères. Ann. Endocrinol., 1998b; 59: 79–92.

  13. 13.

    CARREAU S., GENISSEL C., BILINSKA B., LEVALLET J. The oestrogen sources in the testis and the reproductive tract of the male. Int. J. Androl., sous presse, 1999.

  14. 14.

    CHAN S.Y.W., WANG C.C.L., TANG L.C.H. Effect of clomiphene citrate on human spermatozoa motility and fertilizing capacity in vitro. Fertil. Steril., 1985; 43: 773–776.

  15. 15.

    CHENG C.Y., BOETTCHER B. The effect of steroids on the in vitro migration of washed human spermatozoa in modified tyrode’s solution or in fasting human blood serum. Fertil. Steril., 1979; 32: 566–570.

  16. 16.

    CHEW P.C.T., LOGANATH A., PEH K.L., CHOW W.P., GUNASEGARAM R., RATNAM S.S. Concentrations of intracellular sex steroids in human spermatozoa. Arch. Androl., 1993; 30: 165–170.

  17. 17.

    COOKE P.S., YOUNG P., HESS R.A., CUNHA G.R. Estrogen receptor expression in developing epididymis, efferent ductules, and other male reproductive organs. Endocrinology, 1991; 128: 2874–2879.

  18. 18.

    DANZO B.J. Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. Environ. Health Perspect., 1997; 105: 294–301.

  19. 19.

    DURKEE T.J., MUELLER M., ZINAMAN M. Identification of estrogen receptor protein and messenger ribonucleic acid in human spermatozoa. Am. J. Obstet. Gynecol., 1998; 178: 1288–1297.

  20. 20.

    EDDY E.M. WASHBURN T.F., BUNCH D.O. et al. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 1996; 137: 4796–805.

  21. 21.

    ENMARK E., PELTO-HUIKKO M., GRANDIEN K. et al. Human estrogen receptor-β gene structure, chromosomal localization, and expression pattern. J. Clin. Endocrinol. Metab., 1997; 82: 4258–4265.

  22. 22.

    ERGUN S., UNGERFROREN H., HOLSTEIN A.F., DAVIDOFF M.S. Estrogen and progesterone receptors and estrogen receptor-related antigen (ER-D5) in human epididymis. Molec. Reprod. Dev., 1997; 47: 448–455.

  23. 23.

    FISHER C.R., GRAVES K.H., PARLOW A.F., SIMPSON E.R. Characterization of mice deficient in aromatase (ArKo) because of targeted disruption of thecyp 19 gene. Proc. Natl. Acad. Sci. (USA) 1998; 95: 6965–6970.

  24. 24.

    FISHER J.S., MILLAR M.R., MADJIC G., SAUNDERS P.T.K., FRASER H.M., SHARPE R.M. Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood. J. Endocrinol., 1997; 153: 485–495.

  25. 25.

    FISHER J.S., TURNER K.J., FRASER H.M., SAUNDERS P.T.K., BROWN D., SHARPE R.M. Immunoexpression of aquaporin-1 in the efferent ducts of the rat and marmoset monkey during development, its modulation by estrogens, and its possible role in fluid resorption. Endocrinology, 1998; 139: 3935–3945.

  26. 26.

    FOUCAULT P., DROSDOWSKY M.A., CARREAU S. Germ cell and Sertoli cell interactions in human testis: evidence for stimulatory and inhibitory effects. Human Reprod., 1994; 9: 2062–2068.

  27. 27.

    FREE M.J., JAFFE R.A. Collection of rete testis fluid from rats without previous efferent duct ligation. Biol. Reprod., 1979; 20: 269–278.

  28. 28.

    GILL-SHARMA M.K., GOPALKRISHNAN K., BALASINOR N., PARTE P., JAYARAMAN S., JUNEJA H.S. Effects of tamoxifen on the fertility of male rats. J. Reprod. Fertil., 1993; 99: 395–402.

  29. 29.

    GOLDZEIHER J.W., ROBERTS I.S. Identification of estrogen in the human testis. J. Clin. Endocrinol. Metab., 1952; 12: 143–150.

  30. 30.

    GUNASEGARAM R., CHEW P.C.T., LOGANATH A., PEH K.L., RATNAM S.S. A Δ4-3-keto pathway for testosterone synthesis in the human spermatozoa. Arch. Androl., 1998a; 40: 49–57.

  31. 31.

    GUNASEGARAM R., PEH K.L., LOGANATH A., CHEW P.C.T., RATNAM S.S., ARULKUMARAN S. Cytochrome P-450 cholesterol side chain cleavage expression in human spermatozoa. Horm. Metab. Res., 1998; 30: 58–60.

  32. 32.

    HARRIS C.A., HENTTU P., PARKER M.G., SUMPTER J.P. The estrogenic activity of phthalate esters in vitro. Environ. Health Perspect., 1997; 105: 801–811.

  33. 33.

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

  34. 34.

    HESS R.A., BUNICK D., BAHR J.M. Sperm, a source of estrogen. Environ. Health Perspect., 1995; 103: 59–62.

  35. 35.

    HESS R.A., GIST D.H., BUNICK D. et al. Estrogen receptor (α & β) expression in the excurrent ducts of the adult male rat reproductive tract. J. Androl., 1997; 18: 602–611.

  36. 36.

    HESS R.A., BUNICK D., LEE K.H. et al. A role for estrogens in the male reproductive sytem. Nature, 1997; 390: 509–512.

  37. 37.

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

  38. 38.

    INKSTER S., YUE W., BRODIE A. Human testicular aromatase: immunocytochemical and biochemical studies. J. Clin. Endocrinol. Metab., 1995; 80: 1941–1947.

  39. 39.

    JANULIS L., HESS R.A., BUNICK D. et al. Mouse epididymal sperm contains active P450 aromatase which decreases as sperm traverse the epididymis. J. Androl., 1996; 17: 111–116.

  40. 40.

    JANULIS L., BAHR J.M., HESS R.A., JANSEN S., OSAWA Y., BUNICK D. Rat testicular germ cells and epididymal sperm contain active P450 aromatase. J. Androl., 1998; 19: 65–71.

  41. 41.

    JAYLE M.F., SCHOLLER R., SFIKAKIS A., HERON M. Excrétion des phénolstéroïdes et des 17-cétostéroïdes après administration de gonadotropines à des hommes. Clin. Chim. Acta, 1962; 7: 212–20.

  42. 42.

    JENKINS A.D., LECHENE C.P., HOWARDS S.S. The effect of estrogen administration in vivo on the elemental composition of the intraluminal fluids of the seminiferous tubules, rete testis and epididymis of tha rat. J. Androl., 1983; 4: 272–275.

  43. 43.

    KUIPER G.G.J.M., CARLSSON B., GRANDIEN K. et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology, 1997; 138: 863–870.

  44. 44.

    KUIPER G.G.J.M., GUSTAFSSON J.A. The novel estrogen receptor β subtype: potential role in the cell-and promoter-specific actions of estrogens and anti-estrogens. FEBS Lett., 1997; 410: 87–90.

  45. 45.

    KUIPER G.G.J.M., LEMMEN J.G., CARLSSON B. et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 1998; 139: 4252–4263.

  46. 46.

    KUMARI G.L., AALLAG I.S., DAS R.P., DATTA J.K. Regional differences in steroidogenesis and hormone levels in the epididymis and vas deferens of adult rats. Int. J. Androl., 1980; 3: 267–281.

  47. 47.

    LEACH R.B., MADDOCK W.O., TOKUYAMA I., PAULSEN C.A., NELSON W.O. Clinical studies of testicular hormone production. Recent Prog. Horm. Res., 1956; 12: 377–393.

  48. 48.

    LEJEUNE H., SANCHEZ P., SAEZ J.M. Enhancement of long-term testosterone secretion, and steroidogenic enzyme expression in human Leydig cells by coculture with human Sertoli cellenriched preparations. Int. J. Androl., 1998; 21: 129–140.

  49. 49.

    LEVALLET J., CARREAU S. Expression in vitro du gène de l’aromatase dans les cellules testiculaires du rat. C. R. Acad. Sc. (Paris) 1997; 320: 123–129.

  50. 50.

    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.

  51. 51.

    LEVALLET J., DELARUE B., MITTRE H., CARREAU S. Alternative splicing events in the coding region of the P450 aromatase gene in male rat germ cells. J. Molec. Endocrinol., 1998; 20: 305–312.

  52. 52.

    LI H., PAPADOPOULOS V., VIDIC B., DYM M., CULTY M. Regulation of rat testis gonocyte proliferation by platelet-derived growth factor and estradiol identification of signaling mechanisms involved. Endocrinology, 1997; 138: 1289–1298.

  53. 53.

    LUBAHN D.B., MOYER J.S., GOLDING T.S., COUSE J.F., KORACH K.S., SMITHIES O. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc. Natl. Acad. Sci. USA, 1993; 90: 11162–11166.

  54. 54.

    LUCONI M., BONACCORSI L., MAGGI M. et al. Identification and characterization of functional nongenomic progesterone receptors on human sperm membrane. J. Clin. Endocrinol. Metab., 1998; 83: 877–885.

  55. 55.

    MARIE E., VENDRELY E., de REVIERS M., CARREAU S. Stéroides plasmatiques et intratesticulaires: existe-t-il des correlations avec la spermatogenèse chez l’homme fertile et infécond. Ann. Endocrinol., 1995; 56: 337.

  56. 56.

    MARIE E., VENDRELY E, GALERAUD-DENIS I, de REVIERS M, CARREAU S. Increased testicular steroid concentrations in patients with idiopathic infertility and normal FSH levels. Andrologia, soumis.

  57. 57.

    MEISTRICH M.L., HUGUES T.J., BRUCE W.R. Alteration of epididymal sperm transport and maturation in mice by oestrogen and testosterone. Nature 1975; 258: 145–147.

  58. 58.

    McCALMAN C.D., GETSIOS S., FAROOKHI R., BLASCHUK O.W. Estrogens potentiate the stimulatory effects of follicle stimulating hormone on N-cadherin messenger ribonucleic acid levels in cultured mouse Sertoli cells. Endocrinology, 1997; 138: 41–49.

  59. 59.

    Mc LACHLAN R.I., WREFORD N.G., O’DONNELL L., de KRETSER D.M., ROBERTSON D.M. The endocrine regulation of spermatogenesis: independent roles for testosterone and FSH. J. Endocrinol., 1996; 148: 1–9.

  60. 60.

    MORISHIMA A., GRUMBACH M.M., SIMPSON E.R., FISCHER C., QIN K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J. Clin. Endocrinol. Metab., 1995; 80: 3689–3698.

  61. 61.

    MORRISH D.W., VENNER P.M., SIY O., BARRON G., BHARDWAJ D., OUTHET D. Mechanisms of endocrine dysfunction in patients with testicular cancer. J. Natl. Cancer Inst. 1990; 82: 412–8.

  62. 62.

    MOSSELMAN S., POLMAN J., DIJKEMA R. ERβ: identification and characterization of a novel human estrogen receptor. FEBS Lett., 1996; 392: 49–53.

  63. 63.

    NAKAZUMI H., SASANO H., MAEHARA I., OZAKI M., TEZUKA F., ORIKASA S. Estrogen metabolism and impaired spermatogenesis in germ cell tumors of the testis. J. Clin. Endocrinol. Metab., 1996; 81: 1289–1295.

  64. 64.

    NITTA H., BUNICK D., HESS R.A. et al. Germ cells of the mouse testis express P450 aromatase. Endocrinology, 1993; 132: 1396–1401.

  65. 65.

    O’MARCAIGH A., LEDGER G.A., ROCHE P.C., PARISI J.E., ZIMMERMAN D. Aromatase ex-pression in human germinomas with possible biological effects. J. Clin. Endocrinol. Metab. 1996; 80: 3763–6.

  66. 66.

    PAPADOPOULOS V., DROSDOWSKY M.A., CARREAU S. On the existence of two Leydig cell populations in aged human testis. Ann. NY. Acad. Sci., 1987; 513: 356–359.

  67. 67.

    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.

  68. 68.

    PURVIS K., LANDGREN B.M., CEKAN Z., DICZFALUSY E. Indices of gonadal function in the human male. Seminal plasma levels of steroids in normal and pathological conditions. Clin. Endocrinol., 1975; 4: 247–258.

  69. 69.

    REPKE K.R., MATTHES E. Tamoxifen is a Na+ antagonistic inhibitor of Na+/K+ transporting ATPase from tumor and normal cells. J. Enzyme Inhib., 1994; 8: 207–212.

  70. 70.

    RAESIDE J.J. (1969) The isolation of estrone sulphate and estradiol-17β sulphate from stallion testis. Can. J. Biochem., 1969; 47; 811–815.

  71. 71.

    SAEZ J.M. Leydig cells: endocrine, paracrine and autocrine regulation. Endocr. Rev., 1994; 15: 574–626.

  72. 72.

    SAUNDERS P.T.K., FISHER J.S., SHARPE R.M., MILLAR M.R. Expression of oestrogen receptor beta (ERβ) occurs in multiple cell types, including some germ cells, in the rat testis. J. Endocrinol., 1998; 156: R13-R17.

  73. 73.

    SHARPE R.M. Do males rely on female hormones. Nature, 1997; 390: 447–448

  74. 74.

    SHARPE R.M. The roles of oestrogen in the male. TEM, 1998; 9: 371–377

  75. 75.

    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.

  76. 76.

    SIMPSON E.R., MICHAEL M.D., AGARWAL V.R., HINSHELWOOD M.M., BULUN S.E., ZHAO Y. Expression of the CYP 19 (aromatase) gene: an unusual case of alternative promoter usage. FASEB J., 1997; 11: 29–36.

  77. 77.

    SHETTY G., KRISHNAMURTHY H., KRISHNAMURTHY H.N., BHATNAGAR S., MOUDGAL R.N. Effect of estrogen deprivation on the reproductive physiology of male and female primates. J. Steroid Biochem. Molec. Biol. 1997; 61: 157–166.

  78. 78.

    SHETTY G., KRISHNAMURTHY H., KRISHNAMURTHY H.N. et al. Effect of long term treatment with aromatase inhibitor on testicular function of adult male bonnet monkeys. Steroids, 1998; 63: 414–420.

  79. 79.

    SMITH EP, BOYD J, FRANK GR et al. Oestrogen resistance caused by a mutation in the oestrogen receptor gene in man. New Engl. J. Med., 1994; 331: 1056–1061.

  80. 80.

    SONG W.C., QIAN Y., SUN X., NEGISHI M. Cellular localization and regulation of expression of testicular estrogen sulfotransferase. Endocrinology, 1997; 138: 5006–5012.

  81. 81.

    TASH J.S., MEANS A.R. Regulation of protein phosphorylation and motility by cyclic adenosine monophosphate. Biol. Reprod., 1982; 26: 745–763.

  82. 82.

    TASH J.S., MEANS A.R. Ca2+ regulation of sperm axonemal motility. Methods Enzymol., 1987; 139: 808–823.

  83. 83.

    TEA N.T., CASTANIER M., GRENIER J., SCHOLLER R. Taux d’oestrogènes dans le plasma séminal; comparaison avec le spermogramme. Ann. Endocrinol., 1972; 33: 297–298.

  84. 84.

    TONEY W.T., DANZO B.J. Developmental changes and hormonal regulation of estrogen and androgen receptors present in the rabbit epididymis. Biol. Reprod., 1988; 39: 818–828.

  85. 85.

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

  86. 86.

    TSUBOTA T., NITTA H., OSAWA Y et al. Immunolocalization of steroidogenic enzymes, P450scc, 3β-HSD, P450c17, and P450arom in the hokkaido brown bear (Ursus arctos yesoensis) testis. Gen. Comp. Endocrinol., 1993; 92: 439–444.

  87. 87.

    TSUTSUMI I., FUGIMORI K., NAKAMURA R.M., MATHER J.P., ONO T., DIZEREGA G.S. Disruption of seminiferous epithelial function in the rat by ovarian protein. Biol. Reprod., 1987; 36: 451–461.

  88. 88.

    van PELT A.M.M., de ROOIJ D.G., van der BURG B., van der SAAG P.T., GUSTAFSSON J.A., KUIPER G.G.J.M. Ontogeny of estrogen receptor-β expression in rat testis. Endocrinology, 1999; 140: 478–483.

  89. 89.

    VORNBERGER W., PRINS G., MUSTO N.A., SUAREZ-QUIAN C.A. Androgen receptor distribution in rat testis: new implications for androgen regulation of spermatogenesis. Endocrinology, 1994; 134: 2307–2316.

  90. 90.

    YOUNG J., BULUN S.E., AGARWAL V. et al. Aromatase expression in a feminizing adrenocortical tumor. J. Clin. Endocrinol. Metab., 1996; 81: 3173–3176.

  91. 91.

    ZONDEK B. Mass excretion of oestrogenic hormone in the urine of the stallion. Nature, 1934; 193: 209–210.

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Galeraud-Denis, I., Marie, E. & Carreau, S. Estrogènes et spermatozoïdes. Androl. 9, 252–260 (1999). https://doi.org/10.1007/BF03035237

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Mots-clés

  • Estrogènes
  • spermatogenèse
  • spermatozoïde
  • aromatase
  • fertilité
  • homme

Key words

  • Estrogens
  • spermatogenesis
  • spermatozoa
  • aromatase
  • fertility
  • man