Semen quality is influenced by androgen receptor and aromatase gene synergism

Human Reproduction

Volumn 27, Issue 12, 2012, Pages 3385-3392

  Lazaros, L ^a   Xita, N ^a   Takenaka, A ^b   Sofikitis, N ^a   Makrydimas, G ^a   Stefos, T ^a   Kosmas, I ^c   Zikopoulos, K ^a   Hatzi, E ^a   Georgiou, I ^a  

^a UNIVERSITY OF IOANNINA   (Greece)

^b TOTTORI UNIVERSITY   (Japan)

^c 'Hatzikosta' Hospital   (Greece)

Author keywords

androgen receptor; aromatase; CYP19; semen quality; spermatogenesis

Indexed keywords

ANDROGEN RECEPTOR; AROMATASE;

ADULT; ALLELE; ARTICLE; CONTROLLED STUDY; DNA EXTRACTION; DNA POLYMORPHISM; GENE FUNCTION; GENOTYPE; HOMOZYGOTE; HUMAN; MAJOR CLINICAL STUDY; MALE; OLIGOSPERMIA; SEMEN ANALYSIS; SPERMATOZOON MOTILITY;

EID: 84869999787     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/des334     Document Type: Article

References (57)

1. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 1997;277:965-968.
2. Aquila S, Sisci D, Gentile M, Middea E, Siciliano L, Andò S. Human ejaculated spermatozoa contain active P450 aromatase. J Clin Endocrinol Metab 2002;87:3385-3390.
3. Aquila S, Sisci D, Gentile M, Middea E, Catalano S, Carpino A, Rago V, Ando S. Estrogen receptor (ER)a and ERb are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway. J Clin Endocrinol Metabol 2004;89:1443-1451.
4. Berstein LM, Imyanitov EN, Kovalevskij AJ, Maximov SJ, Vasilyev DA, Buslov KG, Sokolenko AP, Iyevleva AG, Chekmariova EV, Thijssen JH. CYP17 and CYP19 genetic polymorphisms in endometrial cancer: association with intratumoral aromatase activity. Cancer Lett 2004; 207:191-196.
5. Carreau S, de Vienne C, Galeraud-Denis I. Aromatase and estrogens in man reproduction: a review and latest advances. Adv Med Sci 2008; 53:139-144.
6. Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 1994;22:3181-3186.
7. Chang C, Chen YT, Yeh SD, Xu Q, Wang RS, Guillou F, Lardy H, Yeh S. Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proc Natl Acad Sci USA 2004;101:6876-6881.
8. Choong CS, Kemppainen JA, Zhou ZX, Wilson EM. Reduced androgen receptor gene expression with first exon CAG repeat expansion. Mol Endocrinol 1996;10:1527-1535.
9. Chow JD, Simpson ER, Boon WC. Alternative 5'-untranslated first exons of the mouse Cyp19A1 (aromatase) gene. J Steroid Biochem Mol Biol 2009;115:115-125.
10. Cude KJ, Dixon SC, Guo Y, Lisella J, Figg WD. The androgen receptor: genetic considerations in the development and treatment of prostate cancer. J Mol Med (Berl) 1999;77:419-426.
11. Culig Z, Hobisch A, Cronauer MV, Hittmair A, Radmayr C, Bartsch G, Klocker H. Activation of the androgen receptor by polypeptide growth factors and cellular regulators. World J Urol 1995;13:285-289.
12. Dadze S, Wieland C, Jakubiczka S, Funke K, Schröder E, Royer-Pokora B, Willers R, Wieacker PF. The size of the CAG repeat in exon 1 of the androgen receptor gene shows no significant relationship to impaired spermatogenesis in an infertile Caucasoid sample of German origin. Mol Hum Reprod 2000;6:207-214.
13. De Gendt K, Swinnen JV, Saunders PT, Schoonjans L, Dewerchin M, Devos A, Tan K, Atanassova N, Claessens F, Lécureuil C et al. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA 2004; 101:1327-1332.
14. Fisher CR, Graves KH, Parlow AF, Simpson ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the CYP19 gene. Proc Natl Acad Sci USA 1998;95:6965-6970.
15. Gennari L, Masi L, Merlotti D, Picariello L, Falchetti A, Tanini A, Mavilia C, Del Monte F, Gonnelli S, Lucani B et al. A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: effects on bone metabolism. J Clin Endocrinol Metab 2004; 89:2803-2810.
16. Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A, Talcott J, Hennekens CH, Kantoff PW. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA 1997;94:3320-3323.
17. Giwercman YL, Xu C, Arver S, Pousette A, Reneland R. No association between the androgen receptor gene CAG repeat and impaired sperm production in Swedish men. Clin Genet 1998;54:435-436.
18. Gould ML, Hurst PR, Nicholson HD. The effects of oestrogen receptors a and b on testicular cell number and steroidogenesis in mice. Reproduction 2007;134:271-279.
19. Griswold MD. Interactions between germ cells and Sertoli cells in the testis. Biol Reprod 1995;52:211-216.
20. Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 1998;9:411-416.
21. Gupta C. Modulation of androgen receptor (AR)-mediated transcriptional activity by EGF in the developing mouse reproductive tract primary cells. Mol Cell Endocrinol 1999;152:169-178.
22. Haiman CA, Hankinson SE, Spiegelman D, De Vivo I, Colditz GA, Willett WC, Speizer FE, Hunter DJ. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Intern J Canc 2000; 87:204-210.
23. Hiort O, Horter T, Schulze W, Kremke B, Sinnecker GH. Male infertility and increased risk of diseases in future generations. Lancet 1999; 354:1907-1908.
24. Holdcraft RW, Braun RE. Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 2004;131:459-467.
25. Hsing AW, Gao YT, Wu G, Wang X, Deng J, Chen YL, Sesterhenn IA, Mostofi FK, Benichou J, Chang C. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res 2000; 60:5111-116.
26. Johnston DS, Russell LD, Friel PJ, Griswold MD. Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 2001; 142:2405-2408.
27. Kimura N, Mizokami A, Oonuma T, Sasano H, Nagura H. Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. J Histochem Cytochem 1993;41:671-678.
28. Lambard S, Galeraud-Denis I, Bouraïma 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.
29. Lambard S, Galeraud-Denis I, Martin G, Levy R, Carreau S. Analysis and significance of mRNA in human ejaculated sperm from normozoospermic donors: relationship to sperm motility and capacitation. Mol Hum Reprod 2004;10:535-541.
30. Lardone MC, Castillo P, Valdevenito R, Ebensperger M, Ronco AM, Pommer R, Piottante A, Castro A. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. Int J Androl 2010;33:650-660.
31. Lazaros L, Xita N, Kaponis A, Zikopoulos K, Sofikitis N, Georgiou I. Evidence for association of sex hormone-binding globulin and androgen receptor genes with semen quality. Andrologia 2008; 40:186-191.
32. Lazaros L, Xita N, Kaponis A, Hatzi E, Plachouras N, Sofikitis N, Zikopoulos K, Georgiou I. The association of aromatase (CYP19) gene variants with sperm concentration and motility. Asian J Androl 2011;13:292-297.
33. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988;240:327-330.
34. Lund A, Tapanainen JS, Lahdetie J, Savontaus ML, Aittomaki K. Long CAG repeats in the AR gene are not associated with infertility in Finnish males. Acta Obstet Gynecol Scand 2003;82:162-166.
35. McAbee MD, Doncarlos LL. Estrogen, but not androgens, regulates androgen receptor messenger ribonucleic acid expression in the developing male rat forebrain. Endocrinology 1999;140:3674-3681.
36. Nitta H, Bunick D, Hess RA, Janulis L, Newton SC, Osawa Y, Shizuta Y, Toda K, Bahr JM. Germ cells of the mouse testis express P450 aromatase. Endocrinology 1993;132:1396-1401.
37. Notini AJ, Davey RA, McManus JF, Bate KL, Zajac JD. Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model. J Mol Endocrinol 2005;35:547-555.
38. O'Donnell L, McLachlan RI, Wreford NG, de Kretser DM, Robertson DM. Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium. Biol Reprod 1996; 55:895-901.
39. Rajpert-DeMeyts E, Leffers H, Petersen JH, Andersen AG, Carlsen E, Jorgensen N, Skakkebaek NE. CAG repeat length in androgen-receptor gene and reproductive variables in fertile and infertile men. Lancet 2002;359:44-46.
40. Robertson KM, O'Donnell L, Jones ME, Meachem SJ, Boon WC, Fisher CR, Graves KH, McLachlan RI, Simpson ER. Impairment of spermatogenesis in mice lacking a functional aromatase (CYP19) gene. Proc Natl Acad Sci USA 1999;96:7986-7991.
41. Robertson KM, Simpson ER, Lacham-Kaplan O, Jones MEE. Characterization of the fertility of male aromatase knockout mice. J Androl 2001;22:825-830.
42. Rochira V, Granata ARM, 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.
43. Saez JM. Leydig cells: endocrine, paracrine and autocrine regulation. Endocr Rev 1994;15:574-626.
44. Shetty G, Krishnamurthy H, Krishnamurthy HN, Bhatnagar AS, Moudgal NR. Effect of long-term treatment with aromatase inhibitor on testicular function of adult male bonnet monkeys (M. radiata). Steroids 1998;63:414-420.
45. Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994;15:342-355.
46. Solakidi S, Psarra AM, Nikolaropoulos S, Sekeris CE. Estrogen receptors a and b (ERa and ERb) and androgen receptor (AR) in human sperm: localization of ERb and AR in mitochondria of the midpiece. Hum Reprod 2005;20:3481-3487.
47. Stratakis CA, Vottero A, Brodie A, Kirschner LS, DeAtkine D, Lu Q, Yue W, Mitsiades CS, Flor AW, Chrousos GP. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metab 1998;83:1348-1357.
48. Tsutsumi I, Fugimori F, Nakamura JP, Ono T, Dizerega GS. Disruption of seminiferous epithelial function in the rat by ovarian protein. Biol Reprod 1987;36:451-461.
49. Tworoger SS, Chubak J, Aiello EJ, Ulrich CM, Atkinson C, Potter JD, Yasui Y, Stapleton PL, Lampe JW, Farin FM et al. Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2004;13:94-101.
50. Van Golde R, Van Houwelingen K, Kiemeney L, Kremer J, Tuerlings J, Schalken J, Meuleman E. Is increased CAG repeat length in the androgen receptor gene a risk factor for male subfertility? J Urol 2002; 167:621-623.
51. Vornberger W, Prins G, Musto NA, Suarez-Quian CA. Androgen receptor distribution in rat testis: new implications for androgen regulation of spermatogenesis. Endocrinology 1994;134:2307-2316.
52. Wallerand H, Rémy-Martin A, Chabannes E, Bermont L, Adessi GL, Bittard H. Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility. Fertil Steril 2001;76:769-774.
53. Willems A, Batlouni SR, Esnal A, Swinnen JV, Saunders PT, Sharpe RM, França LR, De Gendt K, Verhoeven G. Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development. PLoS One 2010;5:e14168.
54. World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 4th edn. Cambridge, UK: Cambridge University Press, 1999.
55. Yeh S, Chang C. Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Proc Natl Acad Sci USA 1996;93:5517-5521.
56. Zhou Q, Nie R, Prins GS, Saunders PTK, Katzenellenbogen BS, Hess RA. Localization of androgen and estrogen receptors in adult male mouse reproductive tract. J Androl 2002;23:870-881.
57. Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testes: quantitative relationship to testosterone concentration within the testis. Endocrinology 1989; 124:3043-3049.