Formation of the Epididymal Fluid Microenvironment

  • P. Y. D. Wong
  • X. D. Gong
  • G. P. H. Leung
  • B. L. Y. Cheuk


It was thirty years ago when it was demonstrated that spermatozoa have to go through maturational changes in the epididymis before they can fertilize the ovum (Orgebin-Crist, 1967; Bedford, 1967). Since then, there has been a growing focus on the physiology and biochemistry of the epididymis. This burst of epididymal research was largely driven by the recognition that contraceptive agents that interfere with sperm maturation in the epididymis have many advantages over those that suppress sperm production in the testis. The former agents are expected to have a quick onset of action, rapid reversibility upon withdrawal, and reduced chance of mutagenic damage and endocrine impairment of libido. These advantages have been borne out by α-chlorohydrin (Coppola, 1969) and the chlorinated sugars (Ford and Waites, 1980) which act by interfering with sperm metabolism in the epididymis. However, interest in these agents as potential male contraceptives soon waned due to their neurotoxicity. In recent years, the advent of molecular biology techniques has led to t he identification and cloning of genes encoding sperm-coating or epididymal-specific proteins which can be targeted for immunocontraception. However, for these methods to be effective, organ-specific delivery methods of antisense oligonucleotides/antibodies will have to be developed. Reduction of the prominent constituents of the epididymal fluid viz. α-glucosidase and L-carnitine or enhancement of sperm transport through the epididymis by pharmacological means has not led to infertility in animals (Cooper and Yeung, 1999). Despite the consensus held that the epididymis is indispensable for the full expression of male fertility, attempts to induce infertility via an epididymal approach remain elusive.


Cystic Fibrosis Sertoli Cell Cystic Fibrosis Transmembrane Conductance Regulator Efferent Duct Anion Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anguiano, A., Oates, R.D., Amos, J.A., Dean, M., Gerrard, B., Stewart, C., et al, 1992, Congenital bilatera absence of the vas deferens: a primarily genital form of cystic fibrosis. JAMA. 267:1794.PubMedCrossRefGoogle Scholar
  2. Au, C.L., Ngai, H.K., Yeung, C.H. and Wong, P.Y.D., 1978, Effect of adrenalectomy and hormone replaceme on sodium and water transport in the perfused rat cauda epididymidis. J Endocrinol. 77:265.PubMedCrossRefGoogle Scholar
  3. Bedford, J.M., 1967, Effects of duct ligation on the fertilizing ability of spermatozoa from different regions of the rabbit epididymis. J Exp Zool. 166:271.PubMedCrossRefGoogle Scholar
  4. Bertog, M, Smith, D.J., Bielfeld-Ackermann, A., Bassett, J., Ferguson, D.J.P., Korbmacher, C. and Harris, A., 2000, Ovine genital duct epithelial cells differentiate in vitro and express functional CFTR and ENaC. Am J Physiol. In press.Google Scholar
  5. Boockfor, F.R., Morris, R.A., DeSimone, D.C., Hunt, D.M., Walsh, K.B., 1998, Sertoli cell expression of the cystic fibrosis transmembrane conductance regulator. Am J Physiol. 274:C922.PubMedGoogle Scholar
  6. Brugman, S.M. and Taussig, L.M., 1984, The reproductive system, in: Cystic Fibrosis, L.M. Taussig, ed., Thieme-Stratton, New York.Google Scholar
  7. Chan, H.C., Fu, W.O., Chung, Y.W., Huang, S.J., Chan, P. S.F. and W ong, P. Y.D., 1994, Swelling-induced anion and cation conductances in human epididymal cells. J Physiol. 478:449.PubMedGoogle Scholar
  8. Chan, H.C., Fu, W.O., Chung, Y.W., Huang, S.J., Zhou, T.S., and Wong, P.Y.D., 1993, Characterization of a swelling-induced chloride conductance in cultured rat epididymal cells. Am J Physiol. 265:C997.PubMedGoogle Scholar
  9. Chan, H.C., Fu, W.O., Chung, Y.W., Zhou, T.S. and Wong, P.Y.D., 1994, Adrenergic receptors on cultured rat epididymal cells. Regulation of Cl- conductances. Biol Reprod. 51:1040.PubMedCrossRefGoogle Scholar
  10. Chan, H.C., Lai, K.B., Fu, W.O., Chung, Y.W., Chan, P.S.F. and Wong, P.Y.D., 1995, Regional differences in bioelectrical properties and anion secretion in c ultured e pithelia from r at a nd human male excurrent ducts. Biol Reprod. 52:192.PubMedCrossRefGoogle Scholar
  11. Chan, H.C., Zhou, W.L., Fu, W.O., Ko, W.H. and Wong, P.Y.D., 1995, Different regulatory pathways involved in ATP-stimulated chloride secretion in rat epididymal epithelium. J Cell Physiol. 164:271.PubMedCrossRefGoogle Scholar
  12. Chan, H.C., Zhou, W.L. and Wong, P.Y.D., 1995, Extracellular ATP activates both Ca2+- and cAMP- dependent Cl-conductances in rat epididymal cells. J Mem Biol. 147: 185.CrossRefGoogle Scholar
  13. Cheng Chew, S.B., Leung, G.P.H., Leung, P.Y., Tse, C.M. and Wong, P.Y.D., 2000, Polarized distribution of NHE1 and NHE2 in the rat epididymis. Biol Reprod. 62:755.CrossRefGoogle Scholar
  14. Cheung, Y.M., Hwang, J.C. and Wong, P.Y.D., 1977, In vitro measurement of rate of fluid secretion in rat seminiferous tubules: Effects of metabolic inhibitors and ions. J Physiol. 269:1.PubMedGoogle Scholar
  15. Chillion, M., Casals, T., Mercier, B., Bassas, L., Lissens, W., Silber, S., et al., 1995, Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 332:1475.CrossRefGoogle Scholar
  16. Clulow, J., Hansen, L.A. and Jones, R.C., 1996, In vivo microperfusion of the ductuli efferentes testis of the rat: flow dependence of fluid reabsorption. Expl Physiol. 81:633.Google Scholar
  17. Cooper, T.G. and Yeung, C.H., 1999, Recent biochemical approaches to post-testicular, epididymal contraception. Hum Reprod Update. 5:14.CrossRefGoogle Scholar
  18. Coppola, J.A., 1969, An extragonadal male antifertility agent. Life Sci. 8: 43.PubMedCrossRefGoogle Scholar
  19. Corsi, G., Palazzo, G., Germani, C., Barcellona, P.S. and Silvestrini. B., 1976, l-Halobenzyl-lH-indazole-3-carboxylic acids. A new class of antispermatogenic agents. J Med Chem. 19: 778.PubMedCrossRefGoogle Scholar
  20. Cuthbert, A,W. and Wong, P.Y.D., 1986, Electrogenic anion secretion in cultured rat epididymal epithelium. J Physiol. 378:335.PubMedGoogle Scholar
  21. De Braekeleer, M. and Férec, C., 1996, Mutations in the cystic fibrosis gene in men with congenital bilateral absence of the vas deferens. Mol Hum Reprod. 2:669.PubMedCrossRefGoogle Scholar
  22. Denning, C.R., Sommers, S.C. and Quigley, H.J., 1968, Infertility in male patients with cystic fibrosis. Paediatrics 41:7.Google Scholar
  23. Diamond, J.M. and Wright, E.H., 1969, Biological membranes: The physical basis of ion and non-electrolyte selectivity. Ann Rev Physiol. 31:581.CrossRefGoogle Scholar
  24. Ford, W.C.L. and Waites, G.M.H., 1980, The control of male fertility by 6-chloro-6-deoxysugars. Reprod Fert & Develop. 1980; 20:1101.Google Scholar
  25. Hansen, L.A., Clulow, J. and Jones, R.C., 1999, The role of Na+-H+ exchange in fluid and solute transport in the rat efferent ducts. Expl Physiol. 84:521.CrossRefGoogle Scholar
  26. Harris, A., Chalkley, G.C., Lankester, S.A. and Coleman, L.S., 1991, Expression of the cystic fibrosis gene in human development. Development 113:305.PubMedGoogle Scholar
  27. Huang, S.J., Fu, WO., Chung, Y.W., Zhou, T.S. and Wong, P.Y.D., 1993, Properties of cAMP-dependent and Ca2+-dependent whole-cell Cl- conductances in the rat epididymal cells. Am J Physiol. 33:C794.Google Scholar
  28. Ko, W.H., Chan, H.C., Chew, S.B. and Wong, P.Y.D., 1998, Regulated anion secretion in cultured epithelia from Sertoli cells of immature rats. J Physiol. 512:471.PubMedCrossRefGoogle Scholar
  29. Lai, K.B., Fu, W.O., Ko, W.H., Chan, H.C. and Wong, P.Y.D., 1994, The effect of [Arg8]-Vasopressin on electrogenic chloride secretion in cultured rat epididymal epithelia. Am J Physiol. 267:C607.PubMedGoogle Scholar
  30. Langenbach, R., Loftin, C., Lee, C. and Tiano, H., 1999, Cyclooxygenase knockout mice. Models for elucidating isoform-specific functions. Biochem Pharmacol. 58:1237.PubMedCrossRefGoogle Scholar
  31. Leung, AYH., Leung, P.Y., Cheng-Chew, S.B. and Wong, P.Y.D., 1992, The role of calcitonin gene-related peptide in the regulation of anion secretion by the rat and human epididymis. J Endocrinol. 133:259.PubMedCrossRefGoogle Scholar
  32. Leung, A.Y.H., Tai, H.L. and Wong, P.Y.D., 1993, ATP stimulates Ca2+release from a r apidly e xchanging pool in cultured rat epididymal cells. Am J Physiol. 264:C1388.PubMedGoogle Scholar
  33. Leung, A.Y.H. and Wong, P.Y.D., 1992, Studies of transepithelial Cl- transport in cultured cauda epididymal cells of rats by short-circuit current method. J Physiol. 457:391.PubMedGoogle Scholar
  34. Leung, A.Y.H. and Wong, P.Y.D., 1993, Ca2+release in cultured rat epididymal c ells du ring h ypoosmotic swelling. Pflugers Arch. 425:77.PubMedCrossRefGoogle Scholar
  35. Leung, A.Y.H. and Wong, P.Y.D., 1994, Biphasic short-circuit current response to noradrenaline mediated by Ca2+and cyclic AMP in cultured rat epididymal epithelium. Pflügers Arch. 426:396.PubMedCrossRefGoogle Scholar
  36. Leung, A.Y.H., Wong, P.Y.D., Yankaskas, J.R. and Boucher, R.C., 1996, cAMP-regulated but not Ca2+- regulated Cl-is lacking in cystic fibrosis mice epididymides and seminal vesicles. Am J Physiol. 271:C188.PubMedGoogle Scholar
  37. Leung, A.Y.H., Yip, W.K. and Wong, P.Y.D., 1992, Characterization of adrenoceptors involved in the electrogenic chloride secretion by cultured rat epididymal epithelium. Br J Pharmacol. 107:146.PubMedCrossRefGoogle Scholar
  38. Leung, G.P.H. and Wong, P.Y.D., 2000, Activation of cystic fibrosis transmembrane conductance regulator in rat epididymal epithelium by genistein. Biol Reprod. 62:143.PubMedCrossRefGoogle Scholar
  39. Leung, G.P.H., Dun, S.L., Dun, N.J. and Wong, P.Y.D., 1999, Serotonin via 5-HT1Band 5-HT2Breceptors stimulates anion secretion in the rat epididymal epithelium. J Physiol. 519:657.PubMedCrossRefGoogle Scholar
  40. Levine, N. and Marsh, D.J., 1971, Micropuncture studies of the electrochemical aspects of fluid and electrolyte transport in individual seminiferous tubules, the epididymis and the vas deferens in rats. J Physiol. 213:557.PubMedGoogle Scholar
  41. Li, C.S., Black, C, Brideau, C, Chan, C.C., Charleson, S., Cromlish, W.A., et al, 1999, A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett. 9:3181.PubMedCrossRefGoogle Scholar
  42. Man, S .Y., C lulow, J., H ansen, L .A. a nd J ones, R .C, 1997, A drenal independence of fluid and electrolyte reabsorption in the ductuli efferentes testis of the rat. Expl Physiol. 82:283.Google Scholar
  43. Martino, CD., Malcorni, W., Bellocci, M., Floridi, A. and Marcante, M.L., 1981, Effects of AF1312 and lonidamine on mammalian testis. A morphological study. Chemotherapy 27:27.PubMedCrossRefGoogle Scholar
  44. Oates, R.D. and Amos, J.A., 1994, The genetic basis of congenital bilateral absence of the vas deferens and cystic fibrosis. J Androl. 15:1.PubMedGoogle Scholar
  45. Orgebin-Crist M-C., 1967, Sperm maturation in the rabbit epididymis. Nature 216:816.PubMedCrossRefGoogle Scholar
  46. Patrizio, P., Ord, T., Silber, S.J. and Asch, R.H., 1993, Cystic fibrosis mutations impair the fertilization rate of epididymal sperm from men with congenital absence of the vas deferens. Hum Reprod. 8:1259.PubMedGoogle Scholar
  47. Pollard, C.E., Harris, A., Coleman, L. and Argent, B.E., 1991, Chloride channels on epithelial cells from cultured human fetal epididymis. J Mem Biol. 124:275.CrossRefGoogle Scholar
  48. Rave-Harel, N., Kerem, E., Nissim-Rafinia, M., Madjar, I., Goshen, R., Augarten, A., et al, 1997, The molecular basis of partial penetrance of splicing mutations in cystic fibrosis. Am J Hum Genet. 60:87.PubMedGoogle Scholar
  49. Schultz, B.D., Singh, A.K., Devor, D.C. and Bridges, R.J., 1999, Pharmacology of CFTR chloride channel activity. Physiol Rev. 79: S109.PubMedGoogle Scholar
  50. Setchell, B.P., 1967, Fluid secretion by the testis. J Reprod Fert. 14:347CrossRefGoogle Scholar
  51. Setchell, B.P., 1969, Do Sertoli cells secrete the rete testis fluid? J Reprod Fert. 19:391.CrossRefGoogle Scholar
  52. Silvestrini, B., Palazzo, G. and Gregorio, M.D., 1984, Lonidamine and related compounds. Prog Med Chem. 21:111.CrossRefGoogle Scholar
  53. Tizzano, E.F., Silver, M.M., Chitayat, D., Benichou, J.C. and Buchwald, M., 1994, Differential cellular expression of cystic fibrosis transmembrane regulator in the reproductive tissues. Am J Pathol. 144:906.PubMedGoogle Scholar
  54. Trezise, A.E.O. and Buchwald, M., 1991, In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator. Nature 353:434.PubMedCrossRefGoogle Scholar
  55. Trezise, A.E.O., Linder, C.C., Grieger, D., Thompson, E.W., Meunier, H., Griswold, M.D. et al, 1993, CFTR expression is regulated during both the cycle of the seminiferous epithelium and the oestrous cycle of rodents. Nat Genet. 3:157.PubMedCrossRefGoogle Scholar
  56. Tuck, R.R., Setchell, B.P., Waites, G.M.H. and Young, J.A., 1970, The composition of fluid collected by micropuncture and catheterization from the seminiferous tubules and rete testis of rats. Pflügers Arch. 318:225.PubMedCrossRefGoogle Scholar
  57. Turner, T.T., Hartmann, P.K. and Howard, S.S., 1977, In vivo sodium, potassium, and sperm concentrations in the rat epididymis. Fert Steril. 28:191.Google Scholar
  58. Van der Ven, K., Messer, L., van der Ven, H., Jeyendran, R.S. and Ober, C., 1996, Cystic fibrosis mutation screening in healthy men with reduced sperm quality. Hum Reprod. 11:513.PubMedCrossRefGoogle Scholar
  59. Wen, R.Q. and Wong, P.Y.D., 1988, Reserpine treatment increases viscosity of fluid in the epididymis of rats. Biol Reprod. 38:969.PubMedCrossRefGoogle Scholar
  60. Whittle, B.J.R., 1998, Experimental basis for non-steroidal anti-inflammatory drug-induced gut injury, in: Clinical s ignificance and p otentialofs elective COX-2 inh ibitorsJ.R. Vane and R.M. Botting, ed., William Harvey Press, London.Google Scholar
  61. Wong, P.Y.D., 1986, Fluid transport and sperm maturation in the epididymis. Biomed Res. 7 (Suppl 2):233.Google Scholar
  62. Wong, P.Y.D., 1988a, Mechanism of adrenergic stimulation of anion secretion in cultured rat epididymal epithelium. Am J Physiol. 254:121.Google Scholar
  63. Wong, P.Y.D., 1988b, Control of anion and fluid secretion by P2-purinoceptor in the rat epididymis. Br J Pharmacol. 95:1315.PubMedCrossRefGoogle Scholar
  64. Wong, P.Y.D., 1988c, Inhibition by chloride channel blockers of anion secretion in cultured epididymal epithelium and intact epididymis of rats. Br J Pharmacol. 94:155.PubMedCrossRefGoogle Scholar
  65. Wong, P.Y.D., 1989, Potassium channel blockers inhibit anion secretion in cultured rat epididymal epithelium. Jap J Physiol. 39:595.CrossRefGoogle Scholar
  66. Wong, P.Y.D., 1990, Electrolyte and fluid transport in the epididymis, in: Epithelial secretion of water and electrolytesJ.A.Young and P.Y.D.Wong, ed., Springer-Verlag, HeidelbergGoogle Scholar
  67. Wong, P.Y.D., 1998, CFTR gene and male fertility. Mol Hum Reprod. 4:107.PubMedCrossRefGoogle Scholar
  68. Wong, P.Y.D., Au, C.L. and Ngai, H.K., 1979, Some characteristics of salt and water transport in the rat epididymis, in: The SpermatozoonD.W. Fawcett and J.M. Bedford, ed., Urban & Schwarzenberg, Baltimore-Munich.Google Scholar
  69. Wong, P.Y.D. and Chan, T.P.T., 1987, Adrenergic control of electrogenic anion secretion by primary cultures of rat epididymal cells, in: Gastrointestinal and h epatic s ecretionJ.S. Davison and E.A. Shaffer, ed., University of Calgary Press, Canada.Google Scholar
  70. Wong, P.Y.D., Chan, H.C., Leung, P.S., Chung, Y.W., Wong, Y.L., Lee, WM., et al., 1999, Regulation of anion secretion by cyclo-oxygenase and prostanoids in cultured epididymal epithelia from the rat. J Physiol. 514:809.PubMedCrossRefGoogle Scholar
  71. Wong, P.Y.D., Fu, W.O. and Huang, S.J., 1989, Endothelin stimulates anion secretion in a cultured epithelium. Br J Pharmacol. 98:191.CrossRefGoogle Scholar
  72. Wong, P.Y.D. and Huang, S.J., 1989, Intracellular pH measurement in primary monolayer cultures of rat epididymal cells. Pflügers Arch. 413:414.PubMedCrossRefGoogle Scholar
  73. Wong, P.Y.D., Huang, S.J., Fu, W.O. and Law, W.K., 1990, Effect of angiotensins on electrogenic anion transport in monolayer cultures of rat epididymis. J Endocrinol. 125:448.Google Scholar
  74. Wong, P.Y.D., Huang, S.J., Leung, A.Y.H., Fu, W.O., Chung, Y.W., Zhou, T.S., et al., 1992, Physiology and pathophysiology of electrolyte transport in the epididymis. In: Spermatogenesis- fertilization-contraception: Molecular, cellular and endocrine events in male reproductionE. Nieschlag and U-F. Habenicht, ed., Springer, Heidelberg.Google Scholar
  75. Wong, P.Y.D. and Lee, W.M., 1982, Effect of spironolactone (aldosterone antagonist) on electrolyte and water content of the cauda epididymidis and fertility of male rats. Biol Reprod. 27:771.PubMedCrossRefGoogle Scholar
  76. Wong, P.Y.D., Lee, W.M., Tsang, A.Y.F., Fu, W.O. and Chan, Q.Q., 1983, Lack of an effect of gossypol on epididymis of the rat. Contraception 27:391.PubMedCrossRefGoogle Scholar
  77. Wong, P.Y.D. and Yeung, C.H., 1977, Hormonal regulation of fluid reabsorption in isolated rat cauda epididymidis. Endocrinology 101:1391.PubMedCrossRefGoogle Scholar
  78. Wong, P.Y.D. and Yeung, C.H., 1978, Absorptive and secretory functions of the perfused rat cauda epididymidis. J Physiol. 275:13.PubMedGoogle Scholar
  79. Zhou, W.L., Leung, P.S., Wong, T.P., Dun, N.J., Won,g P.Y.D. and Chan, H.C., 1997, Local regulation of epididymal anion secretion by pituitary adenylate cyclase-activating polypeptide. J Endocrinol. 154:389.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • P. Y. D. Wong
    • 1
  • X. D. Gong
    • 1
  • G. P. H. Leung
    • 1
  • B. L. Y. Cheuk
    • 1
  1. 1.Department of Physiology, Faculty of MedicineThe Chinese University of Hong KongShatin, N.T.Hong Kong

Personalised recommendations