Skip to main content
  • Revue
  • Physiologie
  • Published:

Sécrétions apocrines et glandes annexes

Apocrine secretion in accessory sex glands

Resume

Le spermatozoïde quittant le testicule est incapable d’activité transcriptionnelle ou traductionnelle. Malgré cela, la composition en macromolécules de la surface du spermatozoïde subit des modifications majeures au cours de son passage dans le tractus reproducteur mâle. Ceci s’explique par l’interaction entre les sécrétions des différentes glandes du tractus reproducteur mâle et le spermatozoïde. Le mécanisme d’ancrage à la surface du spermatozoïde de certaines protéines nouvellement acquises, particulièrement l’ancrage glycosylphosphatidyl inositol, suggère un mode de sécrétion apocrine le long du tractus reproducteur mâle. Ce type de sécrétion a été démontré au niveau de la prostate, du canal déférent et de l’épididyme.

Notre laboratoire s’est penché sur ce phénomène particulièrement au niveau épididymaire. Nous avons montré que l’épithélium épididymaire sécrète par voie apocrine des microvésicules membranaires nommées épididymosomes. somes. Différentes protéines sont associées à ces vésicules riches en cholestérol et en sphingomyéline. Nous avons montré que certaines de ces protéines associées aux épididymosomes sont sélectivement transférées aux spermatozoïdes au cours du transit épididymaire.

En utilisant une approche protéomique, nous avons identifié certaines de ces protéines. Celles-ci comprennent les enzymes impliquées dans la voie métabolique des polyols. Nous avons également mis en évidence les interactions entre le MIF (Macrophage migration Inhibitory Factor) sécrété par l’épididyme et le spermatozoïde. Tant les polyols que le MIF peuvent être impliqués dans le contrôle de la motilité des spermatozoïdes au cours de leur transit épididymaire.

Ces résultats illustrent l’importance de la sécrétion apocrine dans la maturation des spermatozoïdes au cours de leur transit dans le tractus reproducteur mâle.

Abstract

Although differentiated spermatozoa are incapable of transcriptional or translational activity, the macromolecule composition of their surface undergoes major changes during passage in the male reproductive tract. These changes are due to sequential, well orchestrated interactions between male reproductive tract secretions and the spermatozoan, particularly as it travels along the epididymis. Some of the sperm proteins acquired during maturation along the excurrent duct behave as integral membrane proteins. In fact, some epididymis-derived proteins are glycosyl phosphatidylinositol (GPI) anchored to the sperm plasma membrane, which raises the question of the mechanisms by which these proteins are secreted by the epididymal epithelium.

Our laboratory has identified a family of proteins added to the sperm surface during epididymal transit. These proteins are GPI anchored and the deduced amino acid sequences revealed the absence of a signal peptide in the N-terminal sequence of these proteins. These findings suggest that these proteins are secreted in an apocrine manner by the epididymal epithelium. Apocrine secretion involves formation of a cytoplasmic bleb in the apical region of the epithelial cells that is released into the intraluminal compartment. These blebs disintegrate and release small membranous vesicles generically called exosomes or epididymosomes when secreted by the epididymis. These vesicles are rich in sphingomyelin and are characterized by a high cholesterol/phospholipid ratio. Exosomes have also been reported to be secreted by the prostate, epididymis, and vas deferens.

Many proteins are associated with epididymosomes, and some of them are selectively transferred to spermatozoa during epididymal transit. We have identified some of these proteins by a proteomic approach, including an aldose reductase and a sorbitol dehydrogenase, two enzymes involved in the polyol pathway. Another protein associated with epididymosomes that is transferred to spermatozoa is a cytokine called “Macrophage migration Inhibitory Factor”. During epididymal maturation, this protein is associated with the outer dense fibers of the sperm flagellum and modulates the formation of disulfide bonds. It is hypothesized that both the polyol pathway and apocrine secretion of MIF by the epididymal epithelium modulate sperm motility during transit along the male reproductive tract. Further research is needed to understand the functions of other proteins secreted in an apocrine manner by the various glands of the male reproductive tract.

References

  1. AGRAWAL Y., VANHA-PERTTULA T.: Effect of secretory particles in bovine seminal vesicle secretion on sperm motility and acrosome reaction. J. Reprod. Fertil., 1987, 79: 409–419.

    PubMed  CAS  Google Scholar 

  2. ARIENTI G., CARLINI E., DE COSMO A.M. et al.: Prostasome-like particles in stallion semen. Biol. Reprod., 1998, 59: 309–313.

    Article  PubMed  CAS  Google Scholar 

  3. ARIENTI G., CARLINI E., POLCIA A. et al.: Fatty acid pattern of human prostasome lipid. Arch. Biochem. Biophys., 1998, 358: 391–395.

    Article  PubMed  CAS  Google Scholar 

  4. ARIENTI G., CARLINI E., SACCARDI C. et al.: CA. Role of human prostasomes in the activation of spermatozoa. J. Cell Mol. Med., 2004, 8: 77–84.

    Article  PubMed  CAS  Google Scholar 

  5. AUMULLER G., WILHELM B., SEITZ J.: Apocrine secretionfact or artifact? Anat. Anz., 1999, 181: 437–446.

    Article  CAS  Google Scholar 

  6. BERUBE B., LEFIEVRE L., COUTU L. et al.: Regulation of the epididymal synthesis of P26h, a hamster sperm protein. J. Androl., 1996, 17: 104–110.

    PubMed  CAS  Google Scholar 

  7. BERUBE B., SULLIVAN R.: Inhibition of invo fertilization by active immunization of male hamsters against a 26-kDa sperm glycoprotein. Biol. Reprod., 1994, 51: 1255–1263.

    Article  PubMed  CAS  Google Scholar 

  8. BOUE F., BERUBE B., DE LAMIRANDE E. et al.: Human sperm-zona pellucida interaction is inhibited by an antiserum against a hamster sperm protein. Biol. Reprod., 1994, 51: 577–587.

    Article  PubMed  CAS  Google Scholar 

  9. BOUE F., BLAIS J., SULLIVAN R.: Surface localization of P34H an epididymal protein, during maturation, capacitation, and acrosome reaction of human spermatozoa. Biol. Reprod., 1996, 54: 1009–1017.

    Article  PubMed  CAS  Google Scholar 

  10. BOUE F., SULLIVAN R.: Cases of human infertility are associated with the absence of P34H an epididymal sperm antigen. Biol. Reprod., 1996, 54: 1018–1024.

    Article  PubMed  CAS  Google Scholar 

  11. BREITBART H., RUBINSTEIN S.: Characterization of Mg2+-and Ca2+-ATPase activity in membrane vesicles from ejaculated ram seminal plasma. Arch. Androl., 1982, 9: 147–157.

    Article  PubMed  CAS  Google Scholar 

  12. CAFLISCH C.R., DUBOSE T.D. JR.: Effect of vasectomy on in situ pH in rat testis and epididymis. Contraception, 1990, 42 589–595.

    Article  PubMed  CAS  Google Scholar 

  13. CALVIN H.I., YU C.C., BEDFORD J.M.: Effects of epididymal maturation, zinc (II) and copper (II) on the reactive sulfhydryl content of structural elements in rat spermatozoa. Exp. Cell Res., 1973, 81: 333–341.

    Article  PubMed  CAS  Google Scholar 

  14. CHRISTOVA Y., JAMES P., MACKIE A., et al.: Molecular diffusion in sperm plasma membranes during epididymal maturation. Mol. Cell. Endocrinol., 2004, 216: 41–46.

    Article  PubMed  CAS  Google Scholar 

  15. COOPER T.G.: Interactions between epididymal secretions and spermatozoa. J. Reprod. Fertil., 1998, Suppl 53: 119–136.

    Google Scholar 

  16. DASSOULI A., DARNE C., FABRE S. et al.: Vas deferens epithelial cells in subculture: a model to study androgen regulation of gene expression. J. Mol. Endocrinol., 1995, 15: 129–141.

    Article  PubMed  CAS  Google Scholar 

  17. EICKHOFF R., BALDAUF C., KOYRO H.W. et al.: Influence of macrophage migration inhibitory factor (MIF) on the zinc content and redox state of protein-bound sulphydryl groups in rat sperm: indications for a new role of MIF in sperm maturation. Mol. Hum. Reprod., 2004, 10: 605–611.

    Article  PubMed  CAS  Google Scholar 

  18. EICKHOFF R., WILHELM B., RENNEBERG H. et al.: Purification and characterization of macrophage migration inhibitory factor as a release and transfer to spermatozoa. Mol. Med., 2001, 7: 27–35.

    PubMed  CAS  Google Scholar 

  19. FORNES M.W., BARBIERI A., CAVICCHIA J.C.: Morphological and enzymatic study of membrane-bound vesicles from the lumen of the rat epididymis. Andrologia, 1995, 27: 1–5.

    PubMed  CAS  Google Scholar 

  20. FRAILE B., MARTIN R., DE MIGUEL M.P. et al.: Light and electron microscopic immunohistochemical localization of protein gene product 9.5 and ubiquitin immunoreactivities in the human epididymis and vas deferences. Biol. Reprod., 1996, 55: 291–297.

    Article  PubMed  CAS  Google Scholar 

  21. FRENETTE G., LESSSARD C., MADORE E. et al.: Aldose reductase and macrophage migration inhibitory factor are associated with epididymosomes and spermatozoa in the bovine epididymis. Biol. Reprod., 2003, 69: 1586–1592.

    Article  PubMed  CAS  Google Scholar 

  22. FRENETTE G., LESSARD C., SULLIVAN R.: Pelyol pathway along the bovine epididymis. Mol. Reprod. Dev., 2004, 69: 448–456.

    Article  PubMed  CAS  Google Scholar 

  23. FRENETTE G., LESSARD C., SULLIVAN R.: Selected proteins of “prostasome-like particles” from epididymal cauda fluid are transferred to epididymal caput spermatozoa in bull. Biol. Reprod., 2002, 67: 308–313.

    Article  PubMed  CAS  Google Scholar 

  24. FRENETTE G., SLLIVAN R.: Prostasome-like particles are involved in the transfer of P25b from the bovine epididymal fluid to the sperm surface. Mol. Reprod. Dev., 2001, 59: 115–121.

    Article  PubMed  CAS  Google Scholar 

  25. GAUDREAULT C., LEGARE C., BERUBE B. et al.: Hamster sperm protein, p26h: a member of the short-chain dehydrogenase/reductase superfamily. Biol. Reprod., 1999, 61: 264–273.

    Article  PubMed  CAS  Google Scholar 

  26. GAUDREAULT C., MONTFORT L., SULLIVAN R.: Effect of immunization of hamsters against recombinant P26h on fertility rates. Reproduction, 2002, 123: 307–313.

    Article  PubMed  CAS  Google Scholar 

  27. GHOSH M., ROY S.K., CHOWDHURY A.R.: Zinc and copper conent in rat epididymis and vas deferens. Endokrinologie, 1978, 71: 206–209.

    PubMed  CAS  Google Scholar 

  28. GROOS S., WILHELM B., RENNEBERG H. et al.: Simultaneous apocrine and merocrine secretion in the rat coagulating gland.Cell Tissue Res., 1999, 295: 495–504.

    Article  PubMed  CAS  Google Scholar 

  29. GUILLEMETTE C., THABET M., DOMPIERRE L. et al.: Some vasovasostomized men are characterized by low levels of P34H, an epididymal sperm protein. J. Androl., 1999, 20: 214–219.

    PubMed  CAS  Google Scholar 

  30. HERMO L., JACKS D.: Nuture’s ingenuity: bypassing the classical secretory route via apocrine secretion. Mol. Reprod. Dev., 2002, 63: 394–410.

    Article  PubMed  CAS  Google Scholar 

  31. JONES R.: Sperm survival versus degradation in the Mammalian epididymis: a hypothesis. Biol. Reprod., 2004, 71: 1405–1411.

    Article  PubMed  CAS  Google Scholar 

  32. KIRCHHOFF C., HALE G.: Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins during sperm maturation. Mol. Hum. Reprod., 1996, 2: 177–184.

    Article  PubMed  CAS  Google Scholar 

  33. KRAVETS F.G., LEE J., SINGH B. et al.: Prostasomes: current concepts. Prostate, 43, 2000: 169–174.

    Article  PubMed  CAS  Google Scholar 

  34. LEGARE C., BERUBE B., BOUE F. et al.: Hamster sperm antigen P26h is a phosphatidylinositol-anchored protein. Mol. Reprod. Dev., 1999, 52: 225–233.

    Article  PubMed  CAS  Google Scholar 

  35. LEGARE C., GAUDREAULT C., ST-JACQUES S. et al.: P34H sperm protein is preferentially expressed by the human corpus epididymidis.Endocrinology, 1999, 140: 3318–3327.

    Article  PubMed  CAS  Google Scholar 

  36. LEVINE N., KELLY H. Measurement of pH in the epididymis in vivo. J. Reprod. Fertil., 1978, 52: 333–335.

    PubMed  CAS  Google Scholar 

  37. MANIN M., LECHER P., MARTINEZ A., et al.: Exportation of mouse vas deferens protein, a protein without a signal peptide, from mouse vas deferens epithelium: a model of apocrine secretion. Biol. Reprod., 1995, 52: 50–62.

    Article  PubMed  CAS  Google Scholar 

  38. MINELLI A., MORONI M., MARTINEZ E. et al.: Occurrence of prostasome-like membrane vesicles in equine seminal plasma. J. Reprod. Fertil., 1998, 114: 237–243.

    Article  PubMed  CAS  Google Scholar 

  39. MONTFORT L., FRENETTE G., SULLIVAN R.: Sperm-zona pellucida interaction involves a carbonyl reductase activity in the hamster. Mol. Reprod. Dev., 2002, 61: 113–119.

    Article  PubMed  CAS  Google Scholar 

  40. NICKEL W.: The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes. Eur. J. Biochem., 2003, 270: 2109–2119.

    Article  PubMed  CAS  Google Scholar 

  41. PARENT S.L.L., BRINDLE Y., SULLIVAN R.: Bull subfertility is associated with low levels of a sperm membrane antigen. Mol. Reprod. Dev., 1999, 52: 57–65.

    Article  CAS  Google Scholar 

  42. REJRAJI H., VERNET P., DREVET J.R.: GPX5 is present in the mouse caput and cauda epididymidis lumen at three different locations. Mol. Reprod. Dev., 2002, 63: 96–103.

    Article  PubMed  CAS  Google Scholar 

  43. RONQUIST G.: Zinc enrichment in prostasomes. Int. J. Androl., 1998, 21: 233–234.

    Article  PubMed  CAS  Google Scholar 

  44. RONQUIST G., BRODY I., GOTTFRIES A. et al.: An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid-part II. Andrologia, 1978, 10: 427–433.

    PubMed  CAS  Google Scholar 

  45. RONQUIST G., NILSSON B.O.: The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and maligant prostate growth. Prostate Cancer Prostatic Dis., 2004, 7: 21–31.

    Article  PubMed  CAS  Google Scholar 

  46. SAEZ F., FRENETTE G., SULLIVAN R.: Epididymosomes and prostasomes: their roles in posttesticular maturation of the sperm cells. J. Androl., 2003, 24: 149–154.

    PubMed  Google Scholar 

  47. SULLIVAN R.: Male fertility makers, myth or reality. Anim. Reprod. Sci., 2004, 82–8, 341–347.

    Article  CAS  Google Scholar 

  48. SULLIVAN R., BLEAU G.: Interaction between isolated components from mammalian sperm and egg. Gamete Res., 1985, 12: 101–116.

    Article  CAS  Google Scholar 

  49. SULLIVAN R., FRENETTE G., LESSARD C. et al.: Sperm antigen acquisition in the epididymis: A role for epididymosomes. In: Hinton B.T., Turner T. eds. Epididymis III. Charlottesville (VA, USA), Van Doren Company, 2003, 130–136.

    Google Scholar 

  50. SULLIVAN R., ROBITAILLE G.: Heterogeneity of epididymal spermatozoa of the hamster. Gamete Res., 1989, 24: 229–236.

    Article  PubMed  CAS  Google Scholar 

  51. SUTOVSKY P., MORENO R., RAMALHO-SANTOS J. et al.: A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalina epididymis. J. Cell Sci., 2001, 114: 1665–1675.

    PubMed  CAS  Google Scholar 

  52. UTLEG A.G., YI E.C., XIE T. et al.: Proteomic analysis of human prostasomes. Prostate, 2003, 56: 150–161.

    Article  PubMed  CAS  Google Scholar 

  53. YANAGIMACHI R., KAMIGUCHI Y., MIKAMO K. et al.: Maturation of spermatozoa in the epididymis of the Chinese hamster. Am. J. Anat., 1985, 172: 317–330.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert Sullivan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sullivan, R., Frenette, G. & Legare, C. Sécrétions apocrines et glandes annexes. Androl. 15, 35–40 (2005). https://doi.org/10.1007/BF03035188

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03035188

Mots clés

Key words