Physiology and Pathophysiology of Electrolyte Transport in the Epididymis

  • Patrick Y. D. Wong
  • Stephen J. Huang
  • Anskar Y. H. Leung
  • Wai O. Fu
  • Yiu W. Chung
  • Tai S. Zhou
  • Wilson W. K. Yip
  • Winston K. L. Chan
Part of the Schering Foundation Workshop book series (SCHERING FOUND, volume 4)


Although it was eighty years ago that early investigators of the func- tions of the epididymis noted certain differences in the characteristics of the spermatozoa obtained from different regions and proposed that spermatozoa undergo a ‘ripening’ process during their epididymal passage (Tournade 1913), it was not until fifty-five years later that the principle of epididymal maturation of spermatozoa was refined with solid experimental supports (Bedford 1967; Orgebin-Crist 1967, 1969). It is now clear that important maturation changes take place in spermatozoa in the epididymis of most mammals including man and that these changes confer on the sperm the ability to fertilize eggs. Despite this, the mechanisms underlying sperm maturation are still obscure. To date, technological advances have made possible the study of epididymal functions at a cellular and molecular level and have brought light to our understanding of the underlying processes. Significant progress has been made in the area of androgen-regulated genes that control the biosynthesis and secretion of epididymal-specific macromolecules which are integral to the maturation of sperm plasma membrane. Interested readers are referred to the following excellent papers on this topic: Brooks 1987; Ghyselinck et al. 1990; Walker et al. 1990. The present chapter describes some studies made in our own laboratory on epididymal transport of electrolytes and fluid. Undoubtedly, this aspect of epididymal function is equally important for the maintenance of a favourable fluid environment on which sperm maturation and storage depend (Wong et al. 1982; Wong 1986). The introduction of cell culture techniques for the rat (Kierzenbaum et al. 1981, Beyers et al. 1986) and human (Cooper et al. 1990) epididymis facilitated study of the mechanism and regulation of electrolyte transport by the epididymis by the formation of an epithelial sheet on which transepithelial electrical (Cuthbert and Wong 1986; Wong 1988a, 1988b, 1988c), isotope flux (Fu et al. 1990) and microfluorescence (Wong and Huang 1990) measurements can be made on single cells as well as on cell monolayers. Furthermore, epididymal cell culture also permits access of patch-clamp pipettes to the luminal side of the epithelium so that the conductive properties of this membrane and its activation by intracellular messengers can be studied (Cook et a1.1990; Wong 1990c).


Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Exocrine Gland Basolateral Side Electrolyte Transport 
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. Anderson MP, Rich DP, Gregory RJ, Smith AE, Welsh MJ (1991) Generation of cAMP-oporated chloride currents by expression of CFTR. Science 251: 679–682PubMedCrossRefGoogle Scholar
  2. Au CL, Ngai HK, Yeung CH, Wong PYD (1978) Effect of adrenalectomy and hormone replacement on sodium and water transport in the perfused rat cauda epididymidis. J Endocrinol 77: 265–266PubMedCrossRefGoogle Scholar
  3. Bedford JM (1967) Effects of duct ligation on the fertilizing ability of spermatozoa from different regions of the rabbit epididymis. J Exp Zool 166: 271–282PubMedCrossRefGoogle Scholar
  4. Berger HA, Anderson MP, Gregory RJ, Smith AE, Welsh MJ (1991) The single channel basis of CFTR generated chloride currents. Pediatric Pulmonology Supp16: 250Google Scholar
  5. Beyers SW, Hadley MA, Djakiew D, Dym M (1986) Growth and characterization of polarized monolayers of epididymal epithelial cells and Sertoli cells in dual environment chambers. J Androl 7: 59–68Google Scholar
  6. Boucher RC, Cheng EHC, Paradiso AM, Stutts MJ, Knowles MR, Earp HS (1989) Chloride secretory response in cystic fibrosis human airway epithelia. Preservation of calcium but not protein kinase C and A dependent mechanisms. J Clin Invest 84: 1424–1431Google Scholar
  7. Brooks DE (1987) Developmental expression and androgenic regulation of the messenger RNA for major secretory proteins of the rat epididymis. Mol Cell Endocrinol 53: 59–66PubMedCrossRefGoogle Scholar
  8. Cliff WH, Frizzell RA (1990) Seperate Cl-conductances activated by cAMP and Cat+ in Cf -secreting epithelial cells. Proc Natl Acad Sci USA 87: 4956–4960PubMedCrossRefGoogle Scholar
  9. Cohn JA, Melhus O, Vigna SR, Rigby MR, Marino CR. (1991) Immunocytochemical and phosphorylation studies of Cl-TR. Pediatr Pulmonol Supp16: 229Google Scholar
  10. Coleman L, Harris A (1991) Immortalization of male genital duct epithelium: an assay system for the cystic fibrosis gene. J. Cell Sci 98: 85–89PubMedGoogle Scholar
  11. Cook DI, Huang SJ, Wilson SM, Wong PYD, Young JA (1990) Ion channels in the apical membrane of the rat cauda epididymides. J Physiol 423: 57 PGoogle Scholar
  12. Cooper TG, Yeung CH, Meyer R, Schulze S (1990) Maintenance of human epididymal epithelial cell function in monolayer culture. J Reprod Fertil 90: 81–91PubMedCrossRefGoogle Scholar
  13. Cotton CU, Stutts MJ, Knowles MR, Gatzy JT, Boucher RC (1987) Abnormal apical cell membrane in cystic fibrosis respiratory epithelium. An in vitro electrophysiological analysis. J Clin Invest 79: 80–85PubMedCrossRefGoogle Scholar
  14. Cuthbert AW, Wong PYD (1986) Electrogenic anion secretion in cultured rat epididymal epithelium. J Physiol 378: 335–346PubMedGoogle Scholar
  15. Di Sant’Agnese PA, Talamo RC (1967) Pathogenesis and physiopathology of cystic fibrosis of the pancreas: fibrocystic disease of the pancreas (mucoviscidosis). N Engl J Med 277: 1287–1294PubMedCrossRefGoogle Scholar
  16. Donowitz M, Welsh MJ (1986) Ca and cyclic AMP in regulation of intestinal Na, K, and.Cl transport. Annu Rev Physiol 48: 135–150Google Scholar
  17. El-Badawi A, Schenk EA (1967) The distribution of cholinergic and adrenergic nerves in the mammalian epididymis. Am J Anat 121: 1–14PubMedCrossRefGoogle Scholar
  18. Frizzell RA, Rechkemmer G, Shoemaker RL (1986) Altered regulation of air- way epithelial cell chloride channels in cystic fibrosis. Science 233: 558–560PubMedCrossRefGoogle Scholar
  19. Fu WO, Huang SJ, Wilson SM, Wong PYD. (1990) Adrenaline stimulates Rb+ efflux from the apical and basolateral membranes of the cultured epididymal monolayers. J Physiol 423: 50 PGoogle Scholar
  20. Ghyselinck NB, Jimenez C, Lefrancois AM, Dufaure JP (1990) Molecular cloning of cDNA for androgen-regulated proteins secreted by the mouse epididymis. J Mol Endocrinol 4: 5–12PubMedCrossRefGoogle Scholar
  21. Gray MA, Greenwell JR, Argent BE (1988) Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells. J Membr Biol 105: 131–142PubMedCrossRefGoogle Scholar
  22. Gray MA, Pollard CE, Harris A, Colemen L, Greenwell JR, Argent BE (1990) Anion selectivity and block of the small conductance chloride channel on pancreatic duct cells. Am J Physiol 259: 752–761Google Scholar
  23. Handelsman DJ, Conway AJ, Boylan LM, Turtle JR (1984) Young’s syndrome: obstructive azoospermia and chronic sinopulmonary infections. N Engl J Med 310: 3–9PubMedCrossRefGoogle Scholar
  24. Hanley MR, Jackson TR, Cheung WT, Dreher M, Gatti A, Hawkins P, Patterson SI, Vallejo M, Dawson, AP, Thastrup 0 (1988) Molecular mechanisms of phospholipid signaling pathways in mammalian nerve cells. Cold Spring Harbor Symp Quant Biol 53: 435–445CrossRefGoogle Scholar
  25. Hendry WF, Knight RK, Whitfield HN, Stanfield AG, Pryse-Davies J, Ryder TA, Pavia D, Bateman JR, Clarke SW (1978) Obstructive azoospermia: respiratory function tests, electron microscopy and the results of surgery. B J Urol 50: 598–604CrossRefGoogle Scholar
  26. Huang SJ, Fu WO, Chung YW, Leung AYH, Wong PYD (1991) Adrenaline stimulates whole-cell chloride current in cultured rat epididymal cells. In: Murakami M, Seo Y, Kuwahara A, Watari H (eds) Ionic basis and energy metabolism of epithelial transport–hot aspects from exocrine secretion. National Institute for Physiological Sciences, Okazaki, Japan, pp. 229–230Google Scholar
  27. Kaplan E, Shwachman H, Perlmutter AD, Rule A, Khaw KT, Holsclaw DS (1968) Reproductive failure in males with cystic fibrosis. N Engl J Med 279: 65–69PubMedCrossRefGoogle Scholar
  28. Kerem B, Rommens JM, Buchanan JA, et al. (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245: 1073–1080PubMedCrossRefGoogle Scholar
  29. Kierzenbaum AL, Lea O, Petrusz P, French FS, Tres LL (1981) Isolation, culture, and immunocytochemical characterization of epididymal epithelial cells from pubertal and adult rats. Proc Natl Acad Sci USA 78: 1675–1679CrossRefGoogle Scholar
  30. Liedtke C (1989) Regulation of chloride transport in epithelia, Annu Rev Physiol 51: 143–160PubMedCrossRefGoogle Scholar
  31. Leung AYH, Leung PY, Cheng-Chew SB, Wong PYD (1992) The role of calcitonin gene-related peptide in the regulation of anion secretion by the rat and human epididymis. J Endocrinol (in press)Google Scholar
  32. Levine N, Marsh DJ (1971) Micropuncture studies of the electrochemical aspects of fluid and electrolyte transport in individual seminiferous tubules, the epididymis and vas deferens in rats. J Physiol 213: 557–570PubMedGoogle Scholar
  33. McCann JD, Matsuda J, Garcia M, Kaczorowski G, Welsh MJ (1990) Basolateral K+ channels in airway epithelia. I. Regulation by Cat+ and blocked by charybdotoxin. Am J Physiol 258: L334–342PubMedGoogle Scholar
  34. Neville E, Brewis R, Yeates WK, Burridge A (1983) Respiratory tract disease and obstructive azoospermia. Thorax 38: 929–933PubMedCrossRefGoogle Scholar
  35. Orgebin-Crist M-C (1967) Sperm maturation in rabbit epididymis. Nature 216: 816–818PubMedCrossRefGoogle Scholar
  36. Orgebin-Crist M-C (1969) Studies on the function of the epididymis. Biol Re-prod 1: 155–175CrossRefGoogle Scholar
  37. Pollard CE, Harris A, Coleman L, Argent BE (1992) Chloride channels on epi- thelial cells cultured from human fetal epididymis. J Mem Biol (in press)Google Scholar
  38. Puchelle E, Gaillard D, Hinnrasky J, Fuchey C, Boutterin MC, Jallat J, Slos P, et al. (1991) Immunocytochemical localization of CFTR in normal and CF human respiratory epithelium. Pediatr Pulmonol Suppl 6: 257Google Scholar
  39. Putney JW Jr (1985) Identification of cellular activation mechanisms associated with salivary secretion. Ann Rev Physiol 48: 75–88CrossRefGoogle Scholar
  40. Reddy MM, Bell CL, Quinton PM (1991) Anion selectivity of Cl-conductance affected by cystic fibrosis as an in vitro diagonstic tool. Pediatric Pulmonology Suppl 6: 251Google Scholar
  41. Rich DP, Anderson MP, Gregory RJ, Cheng SH, Paul S, Jefferson DM et al. (1990) Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature 347: 358–363PubMedCrossRefGoogle Scholar
  42. Riordan JR, Rommens JM, Kerem B, Zielenski J, Lok S, Playsic N, Chou JL, Drumm ML, Iannuzzi MC et al. (1989) Identification of the cystic fibrosis gene: cloning and charcaterization of the complementary DNA. Science 245: 1066–1072PubMedCrossRefGoogle Scholar
  43. Rommens JM, Iannuzzi MC, Kerem B et al. (1989) Identification of the cystic fibrosis gene: chromosomal walking and jumping. Science 243: 1059–1065CrossRefGoogle Scholar
  44. Schoumacher RA, Shoemaker RL, Halm DR, Tallant EA, Wallace RW, Frizzell RA (1987) Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells. Nature 330: 752–754PubMedCrossRefGoogle Scholar
  45. Seale TW, Flux M, Rennert OM (1985) Reproductive defects in patients of both sexes with cystic fibrosis: a review. Am Clin Lab Sci 15: 152–158Google Scholar
  46. Sjöstrand NO (1965) The adrenergic innervation of the vas deferens and the accessory male genital glands. Acta Physiol Scand 65 Suppl 257Google Scholar
  47. Thastrup 0, Dawson AP, Scharff O, Foder B, Cullen PJ, Drobak BK, Bjerrum PJ, Christensen SB, Hanley MR (1989) Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage. Agents Action 27: 17–23CrossRefGoogle Scholar
  48. Tournade A (1913) Différence de motilité des spermatozoides prélevés dans les divers segments de l’épididyme. Comptes Rendu de la Soc de Biologie, Paris 74: 738–740Google Scholar
  49. Turner TT, Hartmann PK, Howards SS (1977) In vivo sodium, potassium, and sperm concentrations in the rat epididymis. Fert Steril 28: 191–194Google Scholar
  50. Walker JE, Jones R, Moore A, Hamilton, DW, Hall L (1990) Analysis of major androgen-regulated cDNA clones from the rat epididymis. Mol Cell Endocrinol 74: 61–68PubMedCrossRefGoogle Scholar
  51. Wang C, So SY, Wong KK, So WWK, Chan SYW (1987) Chronic sinopulmonary disease in Chinese patients with obstructive azoospermia. J Androl 8: 225–229PubMedGoogle Scholar
  52. Welsh MJ (1987) Electrolyte transport by airway epithelia. Physiol Rev 67: 1143–1184PubMedGoogle Scholar
  53. Welsh MJ, Liedtke CM (1986) Chloride and potassium channels in cystic fibrosis airway epithelia. Nature 322: 467–470PubMedCrossRefGoogle Scholar
  54. Wen RQ, Wong PYD (1988) Reserpine treatment increases viscosity of fluid in the epididymis of rats. Biol Reprod 38: 969–974PubMedCrossRefGoogle Scholar
  55. Widdicombe JH, Welsh MJ, Finkbeiner WE (1985) Cystic fibrosis decreases the apical membrane chloride permeability of monolayers cultured from cells of tracheal epithelium. Proc Natl Acad Sci 82: 6167–6171PubMedCrossRefGoogle Scholar
  56. Wong PYD (1986) Fluid transport and sperm maturation in the epididymis. Biomed Res 7, Suppl 2: 233–240Google Scholar
  57. Wong PYD (1988a) Mechanism of adrenergic stimulation of anion secretion in cultured rat epididymal epithelium. Am J Physiol 254: F121 - F133PubMedGoogle Scholar
  58. Wong PYD (1988b) Inhibition by chloride channel blockers of anion secretion in cultured rat epididymal epithelium. Brit J Pharmacol 94: 155–163CrossRefGoogle Scholar
  59. Wong PYD (1988c) Control of anion and fluid secretion by apical P2-purinoceptors in the rat epididymis. Brit J Pharmacol 95: 1315–1312CrossRefGoogle Scholar
  60. Wong PYD (1989) Potassium channel blockers inhibit anion secretion in cultured rat epididymal epithelium. Jap J Physiol 39: 595–607CrossRefGoogle Scholar
  61. Wong PYD (1990) Electrolyte and fluid transport in the epididymis. In: Young JA, Wong PYD (eds) Epithelial secretion of water and electrolytes. Springer Verlag, Berlin, Heidelberg, pp 333–347Google Scholar
  62. Wong PYD, Chan TPT (1988) Adrenergic control of electrogenic anion secretion by primary cultures of rat epididymal cells. In: Davison JS, Shaffer EA (eds) Gastrointestinal and hepatic secretion. University of Calgary Press, Canada, pp. 216–219Google Scholar
  63. Wong PYD, Huang SJ (1989) Intracellular pH measurement in primary mono-layer cultures of rat epididymal cells. Pflügers Arch 413: 414–421PubMedCrossRefGoogle Scholar
  64. Wong PYD, Huang SJ (1990) Secretory agonists stimulate a rise in intracellular cyclic AMP but not Cat+ and inositol phosphates in cultured rat epididymal epithelium. Expl Physiol 75: 321–337Google Scholar
  65. Wong PYD, Uchendu CN (1990) The role of angiotensin-converting enzyme in the rat epididymis. J Endocrinol 125: 457–465PubMedCrossRefGoogle Scholar
  66. Wong PYD, Uchendu CN (1991) Studies of the renin-angiotensin system in primary cultures of the rat epididymis. J Endocrinol, 131: 287–293PubMedCrossRefGoogle Scholar
  67. Wong PYD, Yeung CH (1976) Inhibition by amiloride of the sodium dependent fluid reabsorption in isolated rat cauda epididymidis. Brit. J. Pharmac. 58, 529–532Google Scholar
  68. Wong PYD, Yeung CH (1977a) Hormonal regulation of fluid reabsorption in isolated rat cauda epididymidis. Endocrinol 101: 1391–1397CrossRefGoogle Scholar
  69. Wong PYD, Yeung CH (1977b) Inhibition by a-chlorohydrin of fluid reabsorption in the rat cauda epididymidis. J Reprod Fert 51: 469–471CrossRefGoogle Scholar
  70. Wong PYD, Yeung CH (1977c) Fluid reabsorption in isolated duct of the rat cauda epididymidis. J Reprod Fert 49: 77–81CrossRefGoogle Scholar
  71. Wong PYD, Yeung CH (1978) Absorptive and secretory functions of the per-fused rat cauda epididymidis. J Physiol 275: 13–26PubMedGoogle Scholar
  72. Wong PYD, Yeung CH, Ngai HK (1977) Effect of a-chlorohydrin on transport processes in perfused rat cauda epididymidis. Contraception 16: 637642Google Scholar
  73. Wong PYD, Au CL, Bedford JM (1982) Biology of the scrotum ( II) Suppression by abdominal temperature of transepithelial ion and water transport in the cauda epididymidis. Biol Reprod 26: 683–689Google Scholar
  74. Wong PYD, Fu WO, Huang SJ (1989) Endothelin stimulates anion secretion in a cultured epithelium. Br J Pharmacol 98: 191–196CrossRefGoogle Scholar
  75. Wong PYD, Fu WO, Huang SJ (1990a) Measurement of chloride transport pool in rat epididymal cells using short circuit current transients after bumetanide. In: Wong, PYD, Young JA (eds) Exocrine Secretion H. International Symposium on Exocrine Secretion, Hong Kong, pp 133–138Google Scholar
  76. Wong PYD, Huang SJ, Fu WO, Law WK (1990b) Effect of angiotensins on electrogenic anion transport in monolayer cultures of rat epididymis. J Endocrinol 125: 448–456Google Scholar
  77. Wong PYD, Huang SJ, Jones AO, Cook DI, Young JA (1990c) A large conductance K channel from the apical membrane of the rat epididymal epithelium. Pediatric Pulmonology Suppl 5: 215Google Scholar
  78. Wong PYD, Cheng-Chew SB, Leung PY, Qin DN (1991a) Functional study and immunocytochemical identification of endothelin in cultured epididymal cells and intact epididymis of the rat. J Cardio Pharmacol 17 Suppl 7: S241–244Google Scholar
  79. Wong PYD, Huang SJ, Leung AYH, Fu WO, Chung YW, Chan PSF (1991b) Adrenaline stimulates short-circuit current and whole-cell chloride current in cultured human epididymal cells. Pediatric Pulmonology Suppl 6: 262Google Scholar
  80. Wong PYD, Uchendu CN, Huang SJ, Fu WO, Leung AYH, Chung YW (1991c) Local regulation of of ion transport in the epididymis. In: Murakami M, Seo Y, Kuwahara A, Watari H (eds) Ionic basis and energy metabolism of epithelial transport–hot aspects from exocrine secretion. National Institute for Physiological Sciences, Okazaki Japan, pp 153–156Google Scholar
  81. Wong YC, Wong PYD, Yeung CH (1978) Ultrastructural correlation of water reabsorption in isolated rat cauda epididymidis. Experentia 34: 485–487CrossRefGoogle Scholar
  82. Young D (1970) Surgical treatment of male infertility. J Reprod Fertil 23: 541542Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • Patrick Y. D. Wong
  • Stephen J. Huang
  • Anskar Y. H. Leung
  • Wai O. Fu
  • Yiu W. Chung
  • Tai S. Zhou
  • Wilson W. K. Yip
  • Winston K. L. Chan

There are no affiliations available

Personalised recommendations