Skip to main content

Advertisement

Les approches épididymaires de la contraception masculine

Epididymal approaches to male contraception

Résumé

L’offre en matière de moyens contraceptifs masculins est limitée et, en particulier, à ce jour il n’existe pas de contraception hormonale masculine sur le marché. L’épididyme, dans lequel les spermatozoïdes acquièrent leurs capacités fécondantes et où ils sont stockés, s’avère être un site intéressant à cibler. Cette revue vise à présenter de façon synthétique les quelques pistes prometteuses qui ont émergé ces dernières années.

Abstract

The offer in terms of male contraceptives is rather limited and, in particular, there is still no non hormonal pharmacological contraceptive available to date. Epididymis in which spermatozoa become fertile and are stored constitutes an interesting territory to target. This review aims to present concisely some promising trails that have been pursued these late years.

Références

  1. 1.

    Fathalla MF (2001) The contraceptive technology revolution. In: Raff WK, Fathalla MF, Saad E (eds) New pharmacological approaches to reproductive health and healthy aging. Ernst Schering Research Foundation Workshop Supplement 8. Springer-Verlag, Berlin, pp 69–81

  2. 2.

    Stock G, Habenicht UA (1999) Collaboration between industry and academia-prospects for male fertility control. Int J Gynecol Obstet 67:85–92

  3. 3.

    Page ST, Amory JK, Bremner WJ (2008) Advances in male contraception. Endocr Rev 29:465–493

  4. 4.

    Robaire B, Hinton BT (2002) The epididymis: from molecules to clinical practice. New York: Kluwer Academic/Plenum Publishers, pp 575

  5. 5.

    Cummins JM, Orgebin-Crist MC (1971) Investigations into the fertility of epididymal spermatozoa. Biol Reprod 5:13–19

  6. 6.

    Cornwall GA (2009) New insights into epididymal biology and function. Hum Reprod Update 15: 213–227

  7. 7.

    Sullivan R, Frenette G, Girouard J (2007) Epididymosomes are involved in the acquisition of new sperm proteins during epididymal transit. Asian J Androl 9:483–491

  8. 8.

    Visconti PE, Krapf D, de la Vega-Beltrán JL, et al (2011) Ion channels, phosphorylation and mammalian sperm capacitation. Asian J Androl 13:395–405

  9. 9.

    Saez F, Ouvrier A, Drevet JR (2011) Epididymis cholesterol homeostasis and sperm fertilizing ability. Asian J Androl 13:11–17

  10. 10.

    Noblanc A, Kocer A, Chabory E, et al (2011) Glutathione peroxidases (GPx) at work on epididymal spermatozoa: an example of the dual effect of reactive oxygen species on mammalian male fertilizing ability. J Androl 32:641–650

  11. 11.

    Reyes A, Chavarría ME (1981) Interference with epididymal physiology as possible site of male contraception. Arch Androl 7:159–168

  12. 12.

    Comhaire FH (1994) Male contraception: hormonal, mechanical and other. Hum Reprod 9:586–590

  13. 13.

    Cooper TG, Yeung CH (1999a) Approaches to post-testicular contraception. Asian J Androl 1:29–36

  14. 14.

    Cooper TG, Yeung CH (1999b) Recent biochemical approaches to post-meiotic testicular, epididymal contraception. Hum Reprod update 5:141–152

  15. 15.

    Wang C, Swerdloff RS (2002) Male contraception. Best Pract Res Clin Obstet Gynaecol 16:193–203

  16. 16.

    Cooper TG (2002) The epididymis as a target for male contraception. In: B. Robaire, BT Hinton (eds) The epididymis: from molecules to clinical practice. New York: Kluwer Academic/Plenum Publishers, pp 483–502

  17. 17.

    Khole V (2003) Epididymis as a target for contraception. Indian J Exp Biol 41:764–772

  18. 18.

    Sipilä P, Jalkanen J, Huhtaniemi IT, Poutanen M (2009) Novel epididymal proteins as targets for the development of posttesticular male contraception. Reproduction 137:379–389

  19. 19.

    Jervis KM, Robaire B (2001) Dynamic changes in gene expression along the rat epididymis. Biol Reprod 65:696–703

  20. 20.

    Penttinen J, Pujianto DA, Sipila P, et al (2003) Discovery in silico and characterization in vitro of novel genes exclusively expressed in the mouse epididymis. Mol Endocrinol 17:2138–2151

  21. 21.

    Hsia N, Cornwall GA (2004) DNA microarray analysis of regionspecific gene expression in the mouse epididymis. Biol Reprod 70:448–457

  22. 22.

    Johnston DS, Jelinsky SA, Bang HJ, et al (2005) The mouse epididymal transcriptome: transcriptional profiling of segmental gene expression in the epididymis. Biol Reprod 73:404–413

  23. 23.

    Dacheux JL, Belghazi M, Lanson Y, Dacheux F (2006) Human epididymal secretome and proteome. Mol Cell Endocrinol 250:36–42

  24. 24.

    Oh J, Lee J, Woo JM, et al (2006) Systematic identification and integrative analysis of novel genes expressed specifically or predominantly in mouse epididymis. BMC Genomics 7:314

  25. 25.

    Yuan H, Liu A, Zhang L, et al (2006) Proteomic profiling of regionalized proteins in rat epididymis indicates consistency between specialized distribution and protein functions. J Proteome Res 5:299–307

  26. 26.

    Zhang JS, Liu Q, Li YM, et al (2006) Genome-wide profiling of segmental-regulated transcriptomes in human epididymis using oligo microarray. Mol Cell Endocrinol 250:169–177

  27. 27.

    Sipilä P, Pujianto DA, Shariatmadari R, et al (2006) Differential endocrine regulation of genes enriched in initial segment and distal caput of the mouse epididymis as revealed by genome-wide expression profiling. Biol Reprod 75:240–251

  28. 28.

    Jelinsky SA, Turner TT, Bang HJ, et al (2007) The rat epididymal transcriptome: comparison of segmental gene expression in the rat and mouse epididymides. Biol Reprod 76:561–570

  29. 29.

    Thimon V, Koukoui O, Calvo E, Sullivan R (2007) Regionspecific gene expression profiling along the human epididymis. Mol Hum Reprod 13:691–704

  30. 30.

    Li JY, Wang HY, Liu J, et al (2008) Transcriptome analysis of a cDNA library from adult human epididymis. DNA Res 15:115–122

  31. 31.

    Li J, Liu F, Liu X, et al (2011) Mapping of the human testicular proteome and its relationship with that of the epididymis and spermatozoa. Mol Cell Proteomics 10:M110.004630

  32. 32.

    Kopf GS (2008) Approaches to the identification of new nonhormonal targets for male contraception. Contraception 78:S18–S22

  33. 33.

    Mital P, Hinton BT, Dufour JM (2011) The blood-testis and blood-epididymis barriers are more than just their tight junctions. Biol Reprod 84:851–858

  34. 34.

    Zhang XG, Xu Y, Qian SZ (1987) Injection of copper powder into epididymides via vas deferens on male fertility. Adv Contracept Deliv Syst 3:167–171

  35. 35.

    Skandhan KP (1988) Copper: a possible male contraceptive. Adv Contracept Deliv Syst 4:37–40

  36. 36.

    Fahim MS, Wang M, Sutcu MF, et al (1993) Sterilization of dogs with intra-epididymal injection of zinc arginine. Contraception 47:107–122

  37. 37.

    Yeung CH, Cooper TG (1994) Study of the role of epididymal alpha-glucosidase in the fertility of male rats by the administration of the enzyme inhibitor castanospermine. J Reprod Fertil 102:401–410

  38. 38.

    Hamil KG, Sivashanmugan P, Richardson RT, et al (2000) HE2b and HE2g, new members of an epididymis-specific family of androgen-regulated proteins in human. Endocrinol 141:1245–1253

  39. 39.

    Richardson RT, Sivashanmugan P, Hall SH, et al (2001) Cloning and sequencing of human Eppin: a novel family of protease inhibitors expressed in the epididymis and testis. Gene 270:93–102

  40. 40.

    Ding X, Zhang J, Fei J, et al (2010) Variants of the EPPIN gene affect the risk of idiopathic male infertility in the Han-Chinese population. Hum Reprod 25:1657–1665

  41. 41.

    Denolet E, De Gendt K, Allemeersch J, et al (2006) The effect of a Sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Mol Endocrinol 20:321–334

  42. 42.

    Schauwaers K, De Gendt K, Saunders PTK, et al (2007) Loss of androgen receptor binding to selective androgen response elements causes a reproductive phenotype in a knocking mouse model. Proc Natl Acad Sci USA 104:4961–4966

  43. 43.

    Willems De Gendt K, Allemeersch J, et al (2009) Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression. Int J Androl 38:507–517

  44. 44.

    Yenugu S, Richardson RT, Sivashanmugan P, et al (2004) Antimicrobial activity of human EPPIn, an androgen regulated sperm bound protein with a whey acidic protein motif. Biol Reprod 71:1484–1490

  45. 45.

    Wang Z, Widren EE, Sivashanmugan P, et al (2005) Association of EPPIN with semenogelin on human spermatozoa. Biol Reprod 72:1064–1070

  46. 46.

    Wang Z, Widgren EE, Richardson RT, O’Rand MG (2007a) EPPIN: a molecular strategy for male contraception. In: Roldan E, Gomendio M (eds). Spermatology. Nottingham University Press, Nottingham, UK. Soc Reprod Fert Supplement 65:535–542

  47. 47.

    O’Rand MG, Widgren EE, Wang Z, Richardson RT (2006) EPPIN: an effective target for male contraception. Mol Cell Endocrinol 250:157–162

  48. 48.

    Wang Z, Widgren EE, Richardson RT, O’Rand MG (2007) Characterization of an EPPIN protein complex from human semen and spermatozoa. Biol Reprod 77:476–484

  49. 49.

    Mitra A, Richardson RT, O’Rand MG (2010) Analysis of recombinant human semenogelin as an inhibitor of human sperm motility. Biol Reprod 82:489–498

  50. 50.

    O’Rand MG, Widgeren EE, Hamil KG, et al (2011) Epididymal protein targets: a brief history of the development of EPPIN as a contraceptive. J Androl 32:698–704

  51. 51.

    O’Rand MG, Widgren EE, Sivashanmugan P, et al (2004) Reversible immuno-contraception in male monkeys immunized with EPPIN. Science 306:1189–1190

  52. 52.

    O’Rand MG, Widgren EE, Beyler S, Richardson RT (2009) Inhibition of human sperm motility by contraceptive anti-EPPIN antibodies from infertile male monkeys: effect on cAMP. Biol Reprod 80:279–285

  53. 53.

    Eberspaecher U, Roosterman D, Kratzschmar J, et al (1995) Mouse androgen-dependent epididymal glycoprotein CRISP-1 (DE/AEG): isolation, biochemical characterization, and expression in recombinant form. Mol Reprod Dev 42:157–172

  54. 54.

    Jalkanen J, Huhtaniemi I, Poutanen M (2005) Mouse cysteinerich secretory protein 4 (CRISP4): a member of the Crisp family exclusively expressed in the epididymis in an androgendependent manner. Biol Reprod 72:1268–1274

  55. 55.

    Mizuki N, Sarapata DE, Garcia-Sanz JA, Kasahara M (1992) The mouse male germ cell-specific gene Tpx-1: molecular structure, mode of expression in spermatogenesis, and sequence similarity to two non-mammalian genes. Mamm Genome 3:274–280

  56. 56.

    Haendler B, Kratzschmar J, Theuring F, Schleuning WD (1993) Transcripts for cysteine-rich secretory protein-1 (CRISP-1; DE/ AEG) and the novel related CRISP-3 are expressed under androgen control in the mouse salivary gland. Endocrinology 133:192–198

  57. 57.

    Morissette J, Kratzschmar J, Haendler B, et al (1995) Primary structure and properties of helothermine, a peptide toxin that blocks ryanodine receptors. Biophys J 68:2280–2288

  58. 58.

    Yamazaki Y, Morita T (2004) Structure and function of snake venom cysteine-rich secretory proteins. Toxicol 44:27–31

  59. 59.

    Guo M, Teng M, Niu L, et al (2005) Crystal structure of the cysteine-rich secretory protein STECRISP reveals that the cysteine-rich domain has a K+ channel inhibitor-loke fold. J Biol Chem 280:12405–12412

  60. 60.

    Roberts KP, Ensrud KM, Wooters JL, et al (2006) Epididymal secreted protein CRISP1 and sperm function. Mol Cell Endocrinol 250:122–127

  61. 61.

    Udby L, Bjartell A, Malm J, et al (2005) Characterization and localization of cysteine-rich secretory protein 3 (CRISP-3) in the human male reproductive tract. J Androl 26:333–342

  62. 62.

    Cohen DJ, Da Ros VG, Busso D, et al (2007) Participation of epididymal cysteine-rich secretory proteins in sperm-egg fusion and their potential use for male fertility regulation. Asian J Androl 9:528–532

  63. 63.

    Roberts KP, Wamstad JA, Ensrud KM, Hamilton DW (2003) Inhibition of capacitation-associated tyrosine phosphorylation signaling in rat sperm by epididymal protein Crisp-1. Biol Reprod 69:572–581

  64. 64.

    Busso D, Cohen DJ, Maldera JA, et al (2007) A novel function for CRISP1 in rodent fertilization: involvement in sperm-zona pellucida interaction. Biol Reprod 77:848–854

  65. 65.

    Ellerman DA, Busso D, Maldera JA, Cuasnicú PS (2008) Immunocontraceptive properties of recombinant sperm protein DE: implications for the development of novel contraceptives. Fertil Steril 89:199–205

  66. 66.

    Ellerman DA, Cohen DJ, Weigel Muñoz M, et al (2010) Immunologic behavior of human cysteine-rich secretory protein 1 (hCRISP1) in primates: prospects for immunocontraception. Fertil Steril 93:2551–2556

  67. 67.

    Da Ros VG, Maldera JA, Willis WD, et al (2008) Impaired sperm fertilizing ability in mice lacking Cysteine-RIch Secretory Protein 1 (CRISP1). Dev Biol 320:12–18

  68. 68.

    Cohen DJ, Maldera JA, Vasen G, et al (2011) Epididymal Protein CRISP1 Plays Different Roles During the Fertilization Process. J Androl 32:672–678

  69. 69.

    Boué F, Blais J, Sullivan R (1996) Surface localization of P34H an epididymal protein, during maturation, capacitation, and acrosome reaction of human spermatozoa. Biol Reprod 54:1009–1017

  70. 70.

    Légaré C, Gaudreault C, St-Jacques S, Sullivan R (1999) P34H sperm protein is preferentially expressed by the human corpus epididymidis. Endocrinology 140:3318–3327

  71. 71.

    Boué F, Sullivan R (1996) Cases of human infertility are associated with the absence of P34H an epididymal sperm antigen. Biol Reprod 54:1018–1024

  72. 72.

    Moskovtsev SI, Jarvi K, Légaré C, et al (2007) Epididymal P34H protein deficiency in men evaluated for infertility. Fertil Steril 88:1455–1457

  73. 73.

    Sullivan R, Légaré C, Villeneuve M, et al (2006) Levels of P34H, a sperm protein of epididymal origin, as a predictor of conventional in vitro fertilization outcome. Fertil Steril 85:1557–1559

  74. 74.

    Gaudreault C, Montfort L, Sullivan R (2002) Effect of immunization of hamsters against recombinant P26h on fertility rates. Reproduction 123:307–313

  75. 75.

    Dubé E, Legaré C, Gaudreault C, Sullivan R (2005) Contraceptive responses of female hamsters immunized with recombinant sperm protein P26h. Contraception 72:459–467

  76. 76.

    Khan SA, Suryawanshi AR, Ranpura SA, et al (2009) Identification of novel immuno-dominant epididymal sperm proteins using combinatorial approach. Reproduction 138:81–93

  77. 77.

    Khan SA, Jadhav SV, Suryawanshi AR, et al (2011) Evaluation of contraceptive potential of a novel epididymal sperm protein SFP2 in a mouse model. Am J Reprod Immunol 66:185–198

  78. 78.

    Jones R, Mann T, Sherins RJ (1978) Adverse effects of peroxidized lipid on human spermatozoa. Proc R Soc Lond B 201:413–417

  79. 79.

    Jones R, Mann T, Sherins RJ (1979) Peroxidative breakdown of phospholipids in human spermatozoa: spermicidal effects of fatty acid peroxides and protective action of seminal plasma. Fertil Steril 31:531–537

  80. 80.

    Alvarez JG, Touchstone JC, Blasco L, Storey BT (1987) Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. J Androl 8:338–348

  81. 81.

    Aitken RJ, Clarkson JS (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. The Walpole Lecture. J Reprod Fertil 83:459–469

  82. 82.

    Aitken RJ, Fisher H (1994) Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. Bioassays 16:259–268

  83. 83.

    Gomez E, Irvine DS, Aitken RJ (1998) Evaluation of a spectrophotometris assay for the measurement of malonyldialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function. Int J Androl 21:81–94

  84. 84.

    Sharma RK, Agarwal A (1996) Role of reactive oxygen species in male infertility. Urology 48:835–850

  85. 85.

    Aitken RJ (1999) The human spermatozoa-a cell in crisis? The Amoroso Lecture. J Reprod Fertil 115:1–7

  86. 86.

    Aitken RJ (2004) Founders’ Lecture. Human spermatozoa: fruit of creation, seeds of doubt. Reprod Fertil Dev 16:655–664

  87. 87.

    Aitken RJ, Clarkson JS, Fishel S (1989) Generation of reactive oxygen species, lipid peroxidation and human sperm function. Biol Reprod 40:183–197

  88. 88.

    Suleiman SA, Elamin AM, Zaki ZMS, et al (1996) Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl 17:530–537

  89. 89.

    MacLeod J (1943) The role of oxygen in the metabolism and motility of human spermatozoa. Am J Physiol 138:512–518

  90. 90.

    Aitken RJ (2002) Active oxygen in spermatozoa during epididymal transit. In: Robaire B, Hinton BT (Eds), The epididymis from molecules to clinical practice. Plenum Press, New York, pp 325–328

  91. 91.

    Aitken RJ, Harkiss D, Buckingham D (1993) Relationship between iron-catalyzed lipid peroxidation and human sperm function. J Reprod Fertil 98:257–265

  92. 92.

    Aitken RJ, Harkiss D, Buckingham D (1993) Analysis of lipid peroxidation mechanisms in human spermatozoa. Mol Reprod Dev 35:302–315

  93. 93.

    Drevet JR (2011) Protection of epididymal spermatozoa from oxidative stress. In: Agarwal A, Aitken RJ, Alvarez JG (eds) Studies on men’s health and fertility-Oxidative stress in applied basic research and clinical practice. Springer, New York. In press

  94. 94.

    Aitken RJ, Gordon E, Harkiss D, et al (1998) Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 59:1037–1046

  95. 95.

    Chabory E, Damon C, Lenoir A, et al (2009) Epididymis selenoindependent glutathione peroxidase 5 (GPx5) contributes to the maintenance of sperm DNA integrity. J Clin Invest 119:2074–2085

  96. 96.

    Aitken RJ (2009) GPx5 protects the family jewels. J Clin Invest 119:1849–1851

  97. 97.

    Aitken RJ, Koopman P, Lewis SE (2004) Seeds of concern. Nature 432:48–52

  98. 98.

    Vogt PH (2005) Azoospermia factor (AZF) in Yd11: towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod Biomed Online 10:81–93

  99. 99.

    Aitken RJ, Krausz C (2001) Oxidative stress, DNA damage and the Y chromosome. Reproduction 122:497–506

  100. 100.

    Blom E (1966) A new sterilizing and hereditary defect (the « DAG defect ») located in the bull sperm tail. Nature 209:739–740

  101. 101.

    Cooper TG, Barfield JP (2006) Utility of infertile male models for contraception and conservation. Mol Cell Endocrinol 250:206–211

  102. 102.

    Yeung CH, Anapolski M, Cooper TG (2002) Measurement of volume changes in mouse spermatozoa using an electronic sizing analyzer and a flow cytometer: validation and application to an infertile mouse model. J Androl 23:522–528

  103. 103.

    Xu YX, Wagenfeld A, Yeung CH, et al (2003) Expression and location of the taurine transporter in the epididymis of infertile c-ros receptor tyrosine kinase-deficient and fertile heterozygous mice. Mol Reprod Dev 64:144–151

  104. 104.

    Yeung CH, Anapolski M, Setiawan I et al (2004) Effects of putative epididymal osmolytes on sperm volume regulation of fertile and infertile c-ros tarnsgenic mice. J Androl 25:216–223

  105. 105.

    Jeulin C, Lewin LM (1996) Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update 2:87–102

  106. 106.

    Martin CW, Anderson RA, Cheng L, et al (2000) Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations. Hum Reprod 15:637–645

  107. 107.

    Yeung CH, Barfield JP, Cooper TG (2006) Phsyiological volume regulation by spermatozoa. Mol Cell Endcrinol 250:98–105

  108. 108.

    Turner TT (2011) Looking to the Future of Epididymal Research: Why This, Why Now? J Androl 32:705–710

  109. 109.

    Naz RK, Gupta SK, Gupta JC, et al (2005) Recent advances in contraceptive vaccine development: a mini-review. Hum Reprod 20:3271–3283

  110. 110.

    Naz RK (2009) Development of genetically engineered human sperm immuno-contraceptives. J Reprod Immunol 83:145–150

Download references

Author information

Correspondence to J. -R. Drevet.

Rights and permissions

Reprints and Permissions

About this article

Mots clés

  • Épididyme
  • Contrôle de la fertilité

Keywords

  • Epididymis
  • Fertility control