The Blood-Epididymis Barrier and Human Male Fertility

Part of the Advances in Experimental Medicine and Biology book series (AEMB)


Spermatozoa undergo a posttesticular maturation in the epididymis to acquire motility and the capacity to fertilize. Sperm maturation depends in part upon the creation of a specific microenvironment within the epididymal lumen. This environment is conditioned by proteins secreted by the epithelium and by exchange of molecules between the lumen and the blood circulation. These exchanges are selectively regulated by the blood-epididymis barrier. The blood-epididymis barrier is comprised of apical tight junctions between adjacent principal cells. Adherens junctions, which are necessary for cell adhesion, can also be found at the junctional complex present between adjacent principal cells. Progress has been made on the understanding of cellular interactions in the epididymis as well as the regulation of the luminal microenvironment and its importance for sperm maturation in rodents and humans. Clearly, changes in the function of cellular junctions in the human epididymis are associated with male infertility.


Tight Junction Adherens Junction Tight Junction Protein Principal Cell Efferent Duct 
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. 1.
    Orgebin-Crist MC. Maturation of spermatozoa in the rabbit epididymis: delayed fertilization in does inseminated with epididymal spermatozoa. J Reprod Fertil 1968; 16(1):29–33.PubMedGoogle Scholar
  2. 2.
    Bedford JM. Morphological changes in rabbit spermatozoa during passage through the epididymis. J Reprod Fertil 1963; 5:169–177.PubMedGoogle Scholar
  3. 3.
    Turner TT. De Graaf’s thread: the human epididymis. J Androl 2008; 29(3):237–250.PubMedGoogle Scholar
  4. 4.
    Yeung CH, Cooper TG, Bergmann M et al. Organization of tubules in the human caput epididymidis and the ultrastructure of their epithelia. Am J Anat 1991; 191(3):261–279.PubMedGoogle Scholar
  5. 5.
    Vendrely E, Dadoune JP. Quantitative ultrastructural analysis of the principal cells in the human epididymis. Reprod Nutr Dev 1988; 28(5):1225–1235.PubMedGoogle Scholar
  6. 6.
    Yeung CH, Nashan D, Sorg C et al. Basal cells of the human epididymis-antigenic and ultrastructural similarities to tissue-fixed macrophages. Biol Reprod 1994; 50(4):917–926.PubMedGoogle Scholar
  7. 7.
    Robaire B, Hinton B, Orgebin-Crist M-C. The epididymis. In: Neill JD, eds. Knobil and Neill’s Physiology of Reproduction, 3th ed. New York: Elsevier, 2006:1071–1148.Google Scholar
  8. 8.
    Hermo L, Robaire B. Epididymal cell types and their functions. In: Robaire B, Hinton B, eds. The epididymis: from molecules to clinical practice. New York: Plenum Press, 2002:81–102.Google Scholar
  9. 9.
    Robaire B, Hermo L. Efferent ducts, epididymis and vas deferens: structure, functions and their regulation. In: Knobil E, Neill J, eds. The Physiology of Reproduction. New York: Raven Press, 1988:999–1080.Google Scholar
  10. 10.
    Cornwall GA. New insights into epididymal biology and function. Hum Reprod Update 2009; 15(2):213–227.PubMedGoogle Scholar
  11. 11.
    Misell LM, Holochwost D, Boban D et al. A stable isotope-mass spectrometric method for measuring human spermatogenesis kinetics in vivo. J Urol 2006; 175(1):242–246; discussion 246.PubMedGoogle Scholar
  12. 12.
    Hinrichsen MJ, Blaquier JA. Evidence supporting the existence of sperm maturation in the human epididymis. J Reprod Fertil 1980; 60(2):291–294.PubMedGoogle Scholar
  13. 13.
    Dacheux JL, Paquignon M. Relations between the fertilizing ability, motility and metabolism of epididymal spermatozoa. Reprod Nutr Dev 1980; 20(4A):1085–1099.PubMedGoogle Scholar
  14. 14.
    Yeung CH, Cooper TG, Oberpenning F et al. Changes in movement characteristics of human spermatozoa along the length of the epididymis. Biol Reprod 1993; 49(2):274–280.PubMedGoogle Scholar
  15. 15.
    Yeung CH, Perez-Sanchez F, Soler C et al. Maturation of human spermatozoa (from selected epididymides of prostatic carcinoma patients) with respect to their morphology and ability to undergo the acrosome reaction. Hum Reprod Update 1997; 3(3):205–213.PubMedGoogle Scholar
  16. 16.
    Kirchhoff C, Pera I, Derr P et al. The molecular biology of the sperm surface. Post-testicular membrane remodelling. Adv Exp Med Biol 1997; 424:221–232.PubMedGoogle Scholar
  17. 17.
    Cooper TG. The human epididymis, sperm maturation and storage. Official Journal of the hellenic society of andrology 2007; 9(1):18–24.Google Scholar
  18. 18.
    Patrizio P, Ord T, Silber SJ et al. Correlation between epididymal length and fertilization rate in men with congenital absence of the vas deferens. Fertil Steril 1994; 61(2):265–268.PubMedGoogle Scholar
  19. 19.
    Dacheux JL, Gatti JL, Dacheux F. Contribution of epididymal secretory proteins for spermatozoa maturation. Microsc Res Tech 2003; 61(1):7–17.PubMedGoogle Scholar
  20. 20.
    Zhang JS, Liu Q, Li YM et al. Genome-wide profiling of segmental-regulated transcriptomes in human epididymis using oligo microarray. Mol Cell Endocrinol 2006; 250(1–2):169–177.PubMedGoogle Scholar
  21. 21.
    Dacheux JL, Belghazi M, Lanson Y et al. Human epididymal secretome and proteome. Mol Cell Endocrinol 2006; 250(1–2):36–42.PubMedGoogle Scholar
  22. 22.
    Dube E, Chan PT, Hermo L et al. Gene expression profiling and its relevance to the blood-epididymal barrier in the human epididymis. Biol Reprod 2007; 76(6):1034–1044.PubMedGoogle Scholar
  23. 23.
    Thimon V, Koukoui O, Calvo E et al. Region-specific gene expression profiling along the human epididymis. Mol Hum Reprod 2007; 13(10):691–704.PubMedGoogle Scholar
  24. 24.
    Kirchhoff C. Human epididymis-specific gene expression. Official Journal of the hellenic society of andrology 2007; 9(1):25–42.Google Scholar
  25. 25.
    Friend DS, Gilula NB. Variations in tight and gap junctions in mammalian tissues. J Cell Biol 1972; 53(3):758–776.PubMedGoogle Scholar
  26. 26.
    Howards SS, Jessee SJ, Johnson AL. Micropuncture studies of the blood-seminiferous tubule barrier. Biol Reprod 1976; 14(3):264–269.PubMedGoogle Scholar
  27. 27.
    Turner TT, Giles RD, Howards SS. Effect of oestradiol valerate on the rat blood-testis and blood-epididymal barriers to [3H]inulin. J Reprod Fertil 1981; 63(2):355–358.PubMedGoogle Scholar
  28. 28.
    Suzuki F, Nagano T. Development of tight junctions in the caput epididymal epithelium of the mouse. Dev Biol 1978; 63(2):321–334.PubMedGoogle Scholar
  29. 29.
    Cavicchia JC. Fine structure of the monkey epididymis: a correlated thin-section and freeze-cleave study. Cell Tissue Res 1979; 201(3):451–458.PubMedGoogle Scholar
  30. 30.
    Pelletier RM. Freeze-fracture study of cell junctions in the epididymis and vas deferens of a seasonal breeder: the mink (Mustela vison). Microsc Res Tech 1995; 30(1):37–53.PubMedGoogle Scholar
  31. 31.
    Lopez ML, Fuentes P, Retamal C et al. Regional differentiation of the blood-epididymis barrier in stallion (Equus caballus). J Submicrosc Cytol Pathol 1997; 29(3):353–363.PubMedGoogle Scholar
  32. 32.
    Cambrosio Mann M, Friess AE, Stoffel MH. Blood-tissue barriers in the male reproductive tract of the dog: a morphological study using lanthanum nitrate as an electron-opaque tracer. Cells Tissues Organs 2003; 174(4):162–169.PubMedGoogle Scholar
  33. 33.
    Suzuki F, Nagano T. Regional differentiation of cell junctions in the excurrent duct epithelium of the rat testis as revealed by freeze-fracture. Anat Rec 1978; 191(4):503–519.PubMedGoogle Scholar
  34. 34.
    Cyr DG, Robaire B, Hermo L. Structure and turnover of junctional complexes between principal cells of the rat epididymis. Microsc Res Tech 1995; 30(1):54–66.PubMedGoogle Scholar
  35. 35.
    Gonzalez-Mariscal L, Betanzos A, Nava P et al. Tight junction proteins. Prog Biophys Mol Biol 2003; 81(1):1–44.PubMedGoogle Scholar
  36. 36.
    Hoffer AP, Hinton BT. Morphological evidence for a blood-epididymis barrier and the effects of gossypol on its integrity. Biol Reprod 1984; 30(4):991–1004.PubMedGoogle Scholar
  37. 37.
    Hinton BT, Howards SS. Permeability characteristics of the epithelium in the rat caput epididymidis. J Reprod Fertil 1981; 63(1):95–99.PubMedGoogle Scholar
  38. 38.
    Hinton BT, Palladino MA. Epididymal epithelium: its contribution to the formation of a luminal fluid microenvironment. Microsc Res Tech 1995; 30(1):67–81.PubMedGoogle Scholar
  39. 39.
    Chan HC, Lai KB, Fu WO et al. Regional differences in bioelectrical properties and anion secretion in cultured epithelia from rat and human male excurrent ducts. Biol Reprod 1995; 52(1):192–198.PubMedGoogle Scholar
  40. 40.
    Gould SF, Bernstein MH. Fine structure of fetal human testis and epididymis. Arch Androl 1979; 2(2):93–99.PubMedGoogle Scholar
  41. 41.
    Cooper TG, Yeung CH, Meyer R et al. Maintenance of human epididymal epithelial cell function in monolayer culture. J Reprod Fertil 1990; 90(1):81–91.PubMedGoogle Scholar
  42. 42.
    Yeung CH, Cooper TG, Weinbauer GF et al. Fluid-phase transcytosis in the primate epididymis in vitro and in vivo. Int J Androl 1989; 12(5):384–394.PubMedGoogle Scholar
  43. 43.
    Furuse M, Hirase T, Itoh M et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123(6 Pt 2):1777–1788.PubMedGoogle Scholar
  44. 44.
    Cyr DG, Hermo L, Egenberger N et al. Cellular immunolocalization of occludin during embryonic and postnatal development of the mouse testis and epididymis. Endocrinology 1999; 140(8):3815–3825.PubMedGoogle Scholar
  45. 45.
    Levy S, Robaire B. Segment-specific changes with age in the expression of junctional proteins and the permeability of the blood-epididymis barrier in rats. Biol Reprod 1999; 60(6):1392–1401.PubMedGoogle Scholar
  46. 46.
    Gye MC. Expression of occludin in canine testis and epididymis. Reprod Domest Anim 2004; 39(1):43–47.PubMedGoogle Scholar
  47. 47.
    Yoon SI, Park CJ, Nah WH et al. Expression of Occludin in Testis and Epididymis of Wild Rabbits, Lepus sinensis coreanus. Reprod Domest Anim 2009; 44(5):745–750.PubMedGoogle Scholar
  48. 48.
    Furuse M, Itoh M, Hirase T et al. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol 1994; 127(6 Pt 1):1617–1626.PubMedGoogle Scholar
  49. 49.
    Haskins J, Gu L, Wittchen ES et al. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol 1998; 141(1):199–208.PubMedGoogle Scholar
  50. 50.
    Itoh M, Morita K, Tsukita S. Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin. J Biol Chem 1999; 274(9):5981–5986.PubMedGoogle Scholar
  51. 51.
    Saitou M, Fujimoto K, Doi Y et al. Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing tight junctions. J Cell Biol 1998; 141(2):397–408.PubMedGoogle Scholar
  52. 52.
    Ikenouchi J, Furuse M, Furuse K et al. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 2005; 171(6):939–945.PubMedGoogle Scholar
  53. 53.
    Westphal JK, Dorfel MJ, Krug SM et al. Tricellulin forms homomeric and heteromeric tight junctional complexes. Cell Mol Life Sci 67(12):2057–2068.Google Scholar
  54. 54.
    Ikenouchi J, Sasaki H, Tsukita S et al. Loss of occludin affects tricellular localization of tricellulin. Mol Biol Cell 2008; 19(11):4687–4693.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Raleigh DR, Marchiando AM, Zhang Y et al. Tight junction-associated MARVEL proteins marveld3, tricellulin and occludin have distinct but overlapping functions. Mol Biol Cell 21(7):1200–1213.Google Scholar
  56. 56.
    Steed E, Rodrigues NT, Balda MS et al. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC Cell Biol 2009; 10:95.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Morita K, Furuse M, Fujimoto K et al. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci USA 1999; 96(2):511–516.PubMedGoogle Scholar
  58. 58.
    Furuse M, Sasaki H, Fujimoto K et al. A single gene product, claudin-1 or-2, reconstitutes tight junction strands and recruits occludin in fibroblasts. J Cell Biol 1998; 143(2):391–401.PubMedGoogle Scholar
  59. 59.
    Tsukita S, Furuse M. Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol 2000; 149(1):13–16.PubMedGoogle Scholar
  60. 60.
    Van Itallie CM, Anderson JM. Claudins and epithelial paracellular transport. Annu Rev Physiol 2006; 68:403–429.PubMedGoogle Scholar
  61. 61.
    Findley MK, Koval M. Regulation and roles for claudin-family tight junction proteins. IUBMB Life 2009; 61(4):431–437.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Gregory M, Dufresne J, Hermo L et al. Claudin-1 is not restricted to tight junctions in the rat epididymis. Endocrinology 2001; 142(2):854–863.PubMedGoogle Scholar
  63. 63.
    Gregory M, Cyr DG. Identification of multiple claudins in the rat epididymis. Mol Reprod Dev 2006; 73(5):580–588.PubMedGoogle Scholar
  64. 64.
    Guan X, Inai T, Shibata Y. Segment-specific expression of tight junction proteins, claudin-2 and-10, in the rat epididymal epithelium. Arch Histol Cytol 2005; 68(3):213–225.PubMedGoogle Scholar
  65. 65.
    Inai T, Sengoku A, Hirose E et al. Claudin-7 expressed on lateral membrane of rat epididymal epithelium does not form aberrant tight junction strands. Anat Rec (Hoboken) 2007; 290(11):1431–1438.Google Scholar
  66. 66.
    Jelinsky SA, Turner TT, Bang HJ et al. The rat epididymal transcriptome: comparison of segmental gene expression in the rat and mouse epididymides. Biol Reprod 2007; 76(4):561–570.PubMedGoogle Scholar
  67. 67.
    Johnston DS, Jelinsky SA, Bang HJ et al. The mouse epididymal transcriptome: transcriptional profiling of segmental gene expression in the epididymis. Biol Reprod 2005; 73(3):404–413.PubMedGoogle Scholar
  68. 68.
    Mandell KJ, Parkos CA. The JAM family of proteins. Adv Drug Deliv Rev 2005; 57(6):857–867.PubMedGoogle Scholar
  69. 69.
    Ebnet K, Schulz CU, Meyer Zu Brickwedde MK et al. Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem 2000; 275(36):27979–27988.PubMedGoogle Scholar
  70. 70.
    Bazzoni G, Martinez-Estrada OM, Orsenigo F et al. Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin and occludin. J Biol Chem 2000; 275(27):20520–20526.PubMedGoogle Scholar
  71. 71.
    Ebnet K, Suzuki A, Horikoshi Y et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J 2001; 20(14):3738–3748.PubMedGoogle Scholar
  72. 72.
    Ebnet K, Aurrand-Lions M, Kuhn A et al. The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity. J Cell Sci 2003; 116(Pt 19):3879–3891.PubMedGoogle Scholar
  73. 73.
    Liu Y, Nusrat A, Schnell FJ et al. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 2000; 113( Pt 13):2363–2374.PubMedGoogle Scholar
  74. 74.
    Mandell KJ, Berglin L, Severson EA et al. Expression of JAM-A in the human corneal endothelium and retinal pigment epithelium: localization and evidence for role in barrier function. Invest Ophthalmol Vis Sci 2007; 48(9):3928–3936.PubMedCentralPubMedGoogle Scholar
  75. 75.
    Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. Am J Physiol Cell Physiol 2004; 286(6):C1213–1228.PubMedGoogle Scholar
  76. 76.
    Gumbiner B, Lowenkopf T, Apatira D. Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc Natl Acad Sci USA 1991; 88(8):3460–3464.PubMedGoogle Scholar
  77. 77.
    Adachi M, Inoko A, Hata M et al. Normal establishment of epithelial tight junctions in mice and cultured cells lacking expression of ZO-3, a tight-junction MAGUK protein. Mol Cell Biol 2006; 26(23):9003–9015.PubMedCentralPubMedGoogle Scholar
  78. 78.
    Umeda K, Ikenouchi J, Katahira-Tayama S et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 2006; 126(4):741–754.PubMedGoogle Scholar
  79. 79.
    DeBellefeuille S, Hermo L, Gregory M et al. Catenins in the rat epididymis: their expression and regulation in adulthood and during postnatal development. Endocrinology 2003; 144(11):5040–5049.PubMedGoogle Scholar
  80. 80.
    Hirabayashi S, Mori H, Kansaku A et al. MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin. Lab Invest 2005; 85(12):1528–1543.PubMedGoogle Scholar
  81. 81.
    Dobrosotskaya IY, James GL. MAGI-1 interacts with beta-catenin and is associated with cell-cell adhesion structures. Biochem Biophys Res Commun 2000; 270(3):903–909.PubMedGoogle Scholar
  82. 82.
    Hamazaki Y, Itoh M, Sasaki H et al. Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule. J Biol Chem 2002; 277(1):455–461.PubMedGoogle Scholar
  83. 83.
    Jeansonne B et al. Claudin-8 interacts with multi-PDZ domain protein 1 (MUPP1) and reduces paracellular conductance in epithelial cells. Cell Mol Biol (Noisy-le-grand) 2003; 49(1):13–21.Google Scholar
  84. 84.
    Lanaspa MA, Almeida NE, Andres-Hernando A et al. The tight junction protein, MUPP1, is up-regulated by hypertonicity and is important in the osmotic stress response in kidney cells. Proc Natl Acad Sci USA 2007; 104(34):13672–13677.PubMedGoogle Scholar
  85. 85.
    Adachi M, Hamazaki Y, Kobayashi Y et al. Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins. Mol Cell Biol 2009; 29(9):2372–2389.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Cordenonsi M, D’Atri F, Hammar E et al. Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3 and myosin. J Cell Biol 1999; 147(7):1569–1582.PubMedGoogle Scholar
  87. 87.
    D’Atri F, Citi S. Cingulin interacts with F-actin in vitro. FEBS Lett 2001; 507(1):21–24.Google Scholar
  88. 88.
    Guillemot L, Hammar E, Kaister C et al. Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression. J Cell Sci 2004; 117(Pt 22):5245–5256.PubMedGoogle Scholar
  89. 89.
    Guillemot L, Citi S. Cingulin regulates claudin-2 expression and cell proliferation through the small GTPase RhoA. Mol Biol Cell 2006; 17(8):3569–3577.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Ohnishi H, Nakahara T, Furuse K et al. JACOP, a novel plaque protein localizing at the apical junctional complex with sequence similarity to cingulin. J Biol Chem 2004; 279(44):46014–46022.PubMedGoogle Scholar
  91. 91.
    Matter K, Balda MS. Functional analysis of tight junctions. Methods 2003; 30(3):228–234.PubMedGoogle Scholar
  92. 92.
    Gonzalez-Mariscal L, Tapia R, Chamorro D. Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta 2008; 1778(3):729–756.PubMedGoogle Scholar
  93. 93.
    Cyr DG, Gregory M, Dube E et al. Orchestration of occludins, claudins, catenins and cadherins as players involved in maintenance of the blood-epididymal barrier in animals and humans. Asian J Androl 2007; 9(4):463–475.PubMedGoogle Scholar
  94. 94.
    Turner TT, Johnston DS, Finger JN et al. Differential gene expression among the proximal segments of the rat epididymis is lost after efferent duct ligation. Biol Reprod 2007; 77(1):165–171.PubMedGoogle Scholar
  95. 95.
    Dufresne J, Cyr DG. Activation of an SP binding site is crucial for the expression of claudin 1 in rat epididymal principal cells. Biol Reprod 2007; 76(5):825–832.PubMedGoogle Scholar
  96. 96.
    Honda H, Pazin MJ, D’Souza T et al. Regulation of the CLDN3 gene in ovarian cancer cells. Cancer Biol Ther 2007; 6(11):1733–1742.PubMedGoogle Scholar
  97. 97.
    Honda H, Pazin MJ, Ji H et al. Crucial roles of Sp1 and epigenetic modifications in the regulation of the CLDN4 promoter in ovarian cancer cells. J Biol Chem 2006; 281(30):21433–21444.PubMedGoogle Scholar
  98. 98.
    Luk JM, Tong MK, Mok BW et al. Sp1 site is crucial for the mouse claudin-19 gene expression in the kidney cells. FEBS Lett 2004; 578(3):251–256.PubMedGoogle Scholar
  99. 99.
    Sade H, Holloway K, Romero IA et al. Transcriptional control of occludin expression in vascular endothelia: Regulation by Sp3 and YY1. Biochim Biophys Acta 2009; 1789(3):175–183.PubMedGoogle Scholar
  100. 100.
    Hayashi T, Yoshinaga A, Ohno R et al. Expression of the p63 and Notch signaling systems in rat testes during postnatal development: comparison with their expression levels in the epididymis and vas deferens. J Androl 2004; 25(5):692–698.PubMedGoogle Scholar
  101. 101.
    Lopardo T, Lo Iacono N, Marinari B et al. Claudin-1 is a p63 target gene with a crucial role in epithelial development. PLoS ONE 2008; 3(7):e2715.PubMedCentralPubMedGoogle Scholar
  102. 102.
    Ikenouchi J, Furuse M, Furuse K et al. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 2005; 171(6):939–945.PubMedGoogle Scholar
  103. 103.
    Ikenouchi J, Matsuda M, Furuse M et al. Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci 2003; 116(Pt 10):1959–1967.PubMedGoogle Scholar
  104. 104.
    Ohkubo T, Ozawa M. The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation. J Cell Sci 2004; 117(Pt 9):1675–1685.PubMedGoogle Scholar
  105. 105.
    Niessen CM. Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 2007; 127(11):2525–2532.PubMedGoogle Scholar
  106. 106.
    Takai Y, Nakanishi H. Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci 2003; 116(Pt 1):17–27.PubMedGoogle Scholar
  107. 107.
    Watari Y, Kariya K, Shibatohge M et al. Identification of Ce-AF-6, a novel Caenorhabditis elegans protein, as a putative Ras effector. Gene 1998; 224(1–2):53–58.PubMedGoogle Scholar
  108. 108.
    Takahashi K, Nakanishi H, Miyahara M et al. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. J Cell Biol 1999; 145(3):539–549.PubMedGoogle Scholar
  109. 109.
    Okamoto R, Irie K, Yamada A et al. Recruitment of E-cadherin associated with alpha-and beta-catenins and p120ctn to the nectin-based cell-cell adhesion sites by the action of 12-O-tetradecanoylphorbol-13-acetate in MDCK cells. Genes Cells 2005; 10(5):435–445.PubMedGoogle Scholar
  110. 110.
    Fukuhara A, Irie K, Yamada A et al. Role of nectin in organization of tight junctions in epithelial cells. Genes Cells 2002; 7(10):1059–1072.PubMedGoogle Scholar
  111. 111.
    Fukuhara A, Irie K, Nakanishi H et al. Involvement of nectin in the localization of junctional adhesion molecule at tight junctions. Oncogene 2002; 21(50):7642–7655.PubMedGoogle Scholar
  112. 112.
    Sato T, Fujita N, Yamada A et al. Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells. J Biol Chem 2006; 281(8):5288–5299.PubMedGoogle Scholar
  113. 113.
    Honda T, Shimizu K, Fukuhara A et al. Regulation by nectin of the velocity of the formation of adherens junctions and tight junctions. Biochem Biophys Res Commun 2003; 306(1):104–109.PubMedGoogle Scholar
  114. 114.
    Hoshino T, Shimizu K, Honda T et al. A novel role of nectins in inhibition of the E-cadherin-induced activation of Rac and formation of cell-cell adherens junctions. Mol Biol Cell 2004; 15(3):1077–1088.PubMedCentralPubMedGoogle Scholar
  115. 115.
    Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting and tissue morphogenesis. Genes Dev 2006; 20(23):3199–3214.PubMedGoogle Scholar
  116. 116.
    Chen X, Gumbiner BM. Crosstalk between different adhesion molecules. Curr Opin Cell Biol 2006; 18(5):572–578.PubMedGoogle Scholar
  117. 117.
    Cyr DG, Hermo L, Blaschuk OW et al. Distribution and regulation of epithelial cadherin messenger ribonucleic acid and immunocytochemical localization of epithelial cadherin in the rat epididymis. Endocrinology 1992; 130(1):353–363.PubMedGoogle Scholar
  118. 118.
    Andersson AM, Edvardsen K, Skakkebaek NE. Expression and localization of N-and E-cadherin in the human testis and epididymis. Int J Androl 1994; 17(4):174–180.PubMedGoogle Scholar
  119. 119.
    Cyr DG, Robaire B. Developmental regulation of epithelial-and placental-cadherin mRNAs in the rat epididymis. Ann N Y Acad Sci 1991; 637:399–408.PubMedGoogle Scholar
  120. 120.
    Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 2008; 1778(3):660–669.PubMedCentralPubMedGoogle Scholar
  121. 121.
    Barth AI, Nathke IS, Nelson WJ. Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol 1997; 9(5):683–690.PubMedGoogle Scholar
  122. 122.
    Capaldo CT, Macara IG. Depletion of E-cadherin disrupts establishment but not maintenance of cell junctions in Madin-Darby canine kidney epithelial cells. Mol Biol Cell 2007; 18(1):189–200.PubMedCentralPubMedGoogle Scholar
  123. 123.
    Davis MA, Ireton RC, Reynolds AB. A core function for p120-catenin in cadherin turnover. J Cell Biol 2003; 163(3):525–534.PubMedGoogle Scholar
  124. 124.
    Itoh M, Nagafuchi A, Moroi S et al. Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments. J Cell Biol 1997; 138(1):181–192.PubMedGoogle Scholar
  125. 125.
    Merdek KD, Nguyen NT, Toksoz D. Distinct activities of the alpha-catenin family, alpha-catulin and alpha-catenin, on beta-catenin-mediated signaling. Mol Cell Biol 2004; 24(6):2410–2422.PubMedCentralPubMedGoogle Scholar
  126. 126.
    Wiesner C, Winsauer G, Resch U et al. Alpha-catulin, a Rho signalling component, can regulate NF-kappaB through binding to IKK-beta and confers resistance to apoptosis. Oncogene 2008; 27(15):2159–2169.PubMedGoogle Scholar
  127. 127.
    Stemmler MP. Cadherins in development and cancer. Mol Biosyst 2008; 4(8):835–850.PubMedGoogle Scholar
  128. 128.
    Hernandez S, Chavez Munguia B, Gonzalez-Mariscal L. ZO-2 silencing in epithelial cells perturbs the gate and fence function of tight junctions and leads to an atypical monolayer architecture. Exp Cell Res 2007; 313(8):1533–1547.PubMedGoogle Scholar
  129. 129.
    Wittchen ES, Haskins J, Stevenson BR. Exogenous expression of the amino-terminal half of the tight junction protein ZO-3 perturbs junctional complex assembly. J Cell Biol 2000; 151(4):825–836.PubMedGoogle Scholar
  130. 130.
    Lioni M, Brafford P, Andl C et al. Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells. Am J Pathol 2007; 170(2):709–721.PubMedGoogle Scholar
  131. 131.
    Spira A. Epidemiology of human reproduction. Hum Reprod 1986; 1(2):111–115.PubMedGoogle Scholar
  132. 132.
    Chamley LW, Clarke GN. Antisperm antibodies and conception. Semin Immunopathol 2007; 29(2):169–184.PubMedGoogle Scholar
  133. 133.
    Ohl DA, Naz RK. Infertility due to antisperm antibodies. Urology 1995; 46(4):591–602.PubMedGoogle Scholar
  134. 134.
    Flickinger CJ, Howards SS, Herr JC. Effects of vasectomy on the epididymis. Microsc Res Tech 1995; 30(1):82–100.PubMedGoogle Scholar
  135. 135.
    Thimon V, Calvo E, Koukoui O et al. Effects of vasectomy on gene expression profiling along the human epididymis. Biol Reprod 2008; 79(2):262–273.PubMedGoogle Scholar
  136. 136.
    Hermo L, Korah N, Gregory M et al. Structural alterations of epididymal epithelial cells in cathepsin A-deficient mice affect the blood-epididymal barrier and lead to altered sperm motility. J Androl 2007; 28(5):784–797.PubMedGoogle Scholar
  137. 137.
    Dube E, Hermo L, Chan PT et al. Alterations in gene expression in the caput epididymides of nonobstructive azoospermic men. Biol Reprod 2008; 78(2):342–351.PubMedGoogle Scholar
  138. 138.
    Rajasekaran SA, Beyenbach KW, Rajasekaran AK. Interactions of tight junctions with membrane channels and transporters. Biochim Biophys Acta 2008; 1778(3):757–769.PubMedGoogle Scholar
  139. 139.
    Dube E, Hermo L, Chan PT et al. Alterations in the Human Blood-Epididymis Barrier in Obstructive Azoospermia and the Development of Novel Epididymal Cell Lines from Infertile Men. Biol Reprod 2010: In Press.Google Scholar
  140. 140.
    Kim ED, Winkel E, Orejuela F et al. Pathological epididymal obstruction unrelated to vasectomy: results with microsurgical reconstruction. J Urol 1998; 160(6 Pt 1):2078–2080.PubMedGoogle Scholar
  141. 141.
    Calzada MJ. Von Hippel-Lindau syndrome: molecular mechanisms of the disease. Clin Transl Oncol 12(3):160–165.Google Scholar
  142. 142.
    Odrzywolski KJ, Mukhopadhyay S. Papillary cystadenoma of the epididymis. Arch Pathol Lab Med 134(4):630–633.Google Scholar
  143. 143.
    Harten SK, Shukla D, Barod R et al. Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin. Mol Biol Cell 2009; 20(3):1089–1101.PubMedCentralPubMedGoogle Scholar
  144. 144.
    Dube E, Dufresne J, Chan PTK et al. Assessing the role of claudins in maintaining the integrity of epididymal tight junctions using novel human epididymal cell lines. Biology of Reproduction 2010; 82(6):1119–1128.PubMedGoogle Scholar
  145. 145.
    Palladino MA, Powell JD, Korah N et al. Expression and localization of hypoxia-inducible factor-1 subunits in the adult rat epididymis. Biol Reprod 2004; 70(4):1121–1130.PubMedGoogle Scholar
  146. 146.
    Glasker S, Tran MG, Shively SB et al. Epididymal cystadenomas and epithelial tumourlets: effects of VHL deficiency on the human epididymis. J Pathol 2006; 210(1):32–41.PubMedGoogle Scholar
  147. 147.
    Pellati D, Mylonakis I, Bertoloni G et al. Genital tract infections and infertility. Eur J Obstet Gynecol Reprod Biol 2008; 140(1):3–11.PubMedGoogle Scholar
  148. 148.
    Trojian TH, Lishnak TS, Heiman D. Epididymitis and orchitis: an overview. Am Fam Physician 2009; 79(7):583–587.PubMedGoogle Scholar
  149. 149.
    Capaldo CT, Nusrat A. Cytokine regulation of tight junctions. Biochim Biophys Acta 2009; 1788(4):864–871.PubMedCentralPubMedGoogle Scholar
  150. 150.
    Xia W, Mruk DD, Lee WM et al. Cytokines and junction restructuring during spermatogenesis—a lesson to learn from the testis. Cytokine Growth Factor Rev 2005; 16(4–5):469–493.PubMedGoogle Scholar
  151. 151.
    Sawada N, Murata M, Kikuchi K et al. Tight junctions and human diseases. Med Electron Microsc 2003; 36(3):147–156.PubMedGoogle Scholar
  152. 152.
    Sousa S, Lecuit M, Cossart P. Microbial strategies to target, cross or disrupt epithelia. Curr Opin Cell Biol 2005; 17(5):489–498.PubMedGoogle Scholar
  153. 153.
    Araki Y, Suzuki K, Matusik RJ et al. Immortalized epididymal cell lines from transgenic mice overexpressing temperature-sensitive simian virus 40 large T-antigen gene. J Androl 2002; 23(6):854–869.PubMedGoogle Scholar
  154. 154.
    Britan A, Lareyre JJ, Lefrancois-Martinez AM et al. Spontaneously immortalized epithelial cells from mouse caput epididymidis. Mol Cell Endocrinol 2004; 224(1–2):41–53.PubMedGoogle Scholar
  155. 155.
    Dufresne J, St-Pierre N, Viger RS et al. Characterization of a novel rat epididymal cell line to study epididymal function. Endocrinology 2005; 146(11):4710–4720.PubMedGoogle Scholar
  156. 156.
    Sipila P, Shariatmadari R, Huhtaniemi IT et al. Immortalization of epididymal epithelium in transgenic mice expressing simian virus 40 T antigen: characterization of cell lines and regulation of the polyoma enhancer activator 3. Endocrinology 2004; 145(1):437–446.PubMedGoogle Scholar
  157. 157.
    Telgmann R, Brosens JJ, Kappler-Hanno K et al. Epididymal epithelium immortalized by simian virus 40 large T antigen: a model to study epididymal gene expression. Mol Hum Reprod 2001; 7(10):935–945.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2013

Authors and Affiliations

  1. 1.INRS-Institut Armand-FrappierUniversity of QuebecCanada

Personalised recommendations