Blood-Testis Barrier, Junctional and Transport Proteins and Spermatogenesis

  • Brian P. Setchell
Part of the Advances in Experimental Medicine and Biology book series (volume 636)


The term “blood-testis barrier” appears to have been first used by Chiquoine1 in an article on effects of cadmium on the testis, but evidence for such a barrier already existed, dating back to the early years of the twentieth century (see ref. 2 for early references). In a number of studies, it was shown that some dyes when injected into animals, stained most tissues, with the notable exceptions of the brain and the seminiferous tubules of the testis. The former observation was rapidly taken up and developed to form the basis for the concept of the blood-brain barrier3,4, but it was only with the studies of Kormano5 that the true significance of the earlier observations on the testis was recognized. He showed that dyes which were excluded from the tubules of adult rats readily penetrated those of prepubertal animals. In addition, Kormano noticed that staining of interstitial cells with acriflavine also fell around the time of puberty, suggesting a change in the blood vessels as well. At about the same time as Kormano’s studies, Waites and I showed that testis blood flow measured by indicator dilution with rubidium gave much lower values that with iodoantipyrine, while similar values were obtained in most other organs except brain6, suggesting that rubidium was also excluded to some extent from parts of the testis, as it was from the brain.


Germ Cell Sertoli Cell Seminiferous Tubule Seminiferous Epithelium Myoid Cell 
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.
    Chiquoine D. Observations on the early events of cadmium necrosis of the testis. Anat Rec 1964; 149:23–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Setchell BP, Waites GMH. The blood-testis barrier. In: Greep RO, Hamilton DW, eds. Handbook of Physiology Section 7 Vol V. Male Reproductive System. Washington DC: American Physiological Society, 1975:143–172.Google Scholar
  3. 3.
    Davson H, Zlokovic B, Rakic L et al. An Introduction to the Blood-Brain Barrier. London: Macmillan, 1993: 1–335.Google Scholar
  4. 4.
    Rubin LL, Staddon JM. The cell biology of the blood-brain barrier. Annu Rev Neurosci 1999; 22:11–28.PubMedCrossRefGoogle Scholar
  5. 5.
    Kormano M. Dye permeability and alkaline phosphatase activity of testicular capillaries in the post-natal rat. Histochemie 1967; 9:327–338.PubMedCrossRefGoogle Scholar
  6. 6.
    Waites GMH, Setchell BP. Changes in blood flow and vascular permeability in the testis, epididymis and accessory reproductive organs of the rat after the administration of cadmium chloride. J Endocrinol 1966; 34:329–342.PubMedCrossRefGoogle Scholar
  7. 7.
    Voglmayr JK, Waites GMH, Setchell BP. Studies on spermatozoa and fluid collected directly from the testis of the conscious ram. Nature 1966; 210:861–863.PubMedCrossRefGoogle Scholar
  8. 8.
    Voglmayr JK, Scott TW, Setchell BP et al. Metabolism of testicular spermatozoa and characteristics of testicular fluid collected from the conscious ram. J Reprod Fertil 1967; 14:87–99.PubMedGoogle Scholar
  9. 9.
    Setchell BP, Scott TW, Voglmayr JK et al. Characteristics of testicular spermatozoa and the fluid which transports them into the epididymis. Biol Reprod 1969; (Suppl 1):40–66.Google Scholar
  10. 10.
    Tuck RR, Setchell BP, Waites GMH et al. The composition of fluid collected by micropuncture and catheterization from the seminiferous tubules and rete testis of rats. Pflugers Archiv 1970; 318:225–243.PubMedCrossRefGoogle Scholar
  11. 11.
    Setchell BP, Dawson RMC, White RW. The high concentration of free myo-inositol in rete testis fluid from rams. J Reprod Fertil 1968; 17:329–332.Google Scholar
  12. 12.
    Hinton BT, White RW, Setchell BP. Concentrations of myo-inositol in the luminal fluid of the mammalian testis and epididymis. J Reprod Fertil 1980; 58:395–399.PubMedGoogle Scholar
  13. 13.
    Setchell BP, Voglmayr JK, Waites GMH. A blood-testis barrier restricting passage from blood into rete testis fluid but not into lymph. J Physiol 1969; 200:73–85.PubMedGoogle Scholar
  14. 14.
    Setchell BP, Wallace ALC. The penetration of iodine-labelled FSH and albumin into the seminiferous tubules of sheep and rats. J Endocrinol 1972; 54:67–77.PubMedCrossRefGoogle Scholar
  15. 15.
    Waites GMH, Jones AR, Main SJ et al. The entry of antifertility and other compounds into the testis. Adv Biosci 1973; 10:101–116.PubMedGoogle Scholar
  16. 16.
    Setchell BP, Hinton BT, Jacks F et al. Restricted penetration of iodinated follicle-stimulating and luteinizing hormone into the seminiferous tubules of the rat testis. Mol Cell Endocrinol 1976; 6:59–69.PubMedCrossRefGoogle Scholar
  17. 17.
    Howards SS, Jessee SJ, Johnson AL. Micropuncture studies of the blood-seminiferous tubule barrier. Biol Reprod 1976; 14:264–269.PubMedCrossRefGoogle Scholar
  18. 18.
    Fawcett DM. Ultrastructure and function of Sertoli cells. In: Greep RO, Hamilton DW, eds. Handbook of Physiology Section 7 Vol V. Male Reproductive System. Washington DC: American Physiological Society, 1975:21–55.Google Scholar
  19. 19.
    Russell LD, Clegg ED, Ettlin RA et al. Histological and Histopathological Evaluation of the Testis. Clearwater: Cache River Press, 1990: 1–286.Google Scholar
  20. 20.
    Russell LD. Form, dimensions and cytology of mammalian Sertoli cells. In: Russell LD, Griswold MD, eds. The Sertoli cell. Clearwater: Cache River Press, 1993:1–37.Google Scholar
  21. 21.
    Ploen L, Setchell BP. Blood-testis barriers revisited: A homage to Lennart Nicander. Int J Androl 1992; 15:1–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Setchell BP, Pollanen P, Zupp JL. The development of the blood-testis barrier and changes in vascular permeability at puberty in rats. Int J Androl 1988; 11:225–233.PubMedCrossRefGoogle Scholar
  23. 23.
    Setchell BP, Tao L, Zupp JL. The penetration of chromium-EDTA from blood plasma into various compartments of rat testes, as an indicator of the blood-testis barrier, following exposure of the testes to heat. J Reprod Fertil 1996; 106:125–133.PubMedCrossRefGoogle Scholar
  24. 24.
    Tao L, Zupp JL, Setchell BP. Effect of efferent duct ligation on the function of the blood-testis barrier in rats. J Reprod Fertil 2000; 120:13–18.PubMedCrossRefGoogle Scholar
  25. 25.
    Setchell BP. The entry of substances into the seminiferous tubules. In: Mancini RE, Martini L, eds. Male Fertility and Sterility. New York: Academic Press, 1974:37–57.Google Scholar
  26. 26.
    Jones KH, Dechkonskaia AM, Herrick EA et al. Subchronic effects following a single sarin exposure on blood-brain and blood-testes barrier permeability, acetylcholinesterase, and acetylcholine receptors in the central nervous system of rat: A dose-reponse study. J Toxicol Environ Health A 2000; 61:695–797.PubMedCrossRefGoogle Scholar
  27. 27.
    Abou-Donia MB, Goldstein LB, Dechovskaia A et al. Effects of daily dermal application of DEET and epermethrin, alone and in combination on sensimotor performance, blood-brain barrier, and blood-testis barrier in rats. J Toxicol Environ Health A 2001; 62:523–541.PubMedCrossRefGoogle Scholar
  28. 28.
    Malin DH, Lake JR, Schopen CK et al. Nicotine abstinence syndrome precipitated by central but not peripheral hexamethonium. Pharmacol Biochem Behav 1997; 58:695–699.PubMedCrossRefGoogle Scholar
  29. 29.
    Furuta S, Suzuki M, Toyama S et al. Tissue distribution of polaprezinc in rats determined by the double tracer method. J Pharm Biomed Anal 1999; 19:453–461.PubMedCrossRefGoogle Scholar
  30. 30.
    Meng J, Holdcraft RW, Shima JE et al. Androgens regulate the permeability of the blood-testis barrier. Proc Nat Acad Sci USA 2005; 102:16696–16700.PubMedCrossRefGoogle Scholar
  31. 31.
    Banks WA, Kastin AJ. Human interleukin-1α crosses the blood-testis barriers of the mouse. J Androl 1992; 13:254–259.PubMedGoogle Scholar
  32. 32.
    McLay RN, Banks WA, Kastin AJ. Granulocyte macrophage-colony stimulating factor crosses the blood-testis barrier in mice. Biol Reprod 1997; 57:822–826.PubMedCrossRefGoogle Scholar
  33. 33.
    Banks WA, Kastin AJ, Komaki G et al. Pituitary adenylate cyclase activating polypeptide (PACAP) can cross the vascular component of the blood-testis barrier in the mouse. J Androl 1993; 14:170–173.PubMedGoogle Scholar
  34. 34.
    Banks WA, Kastin AJ, Ehrensing CA. Diurnal uptake of circulating interleukin-1α by brain, spinal cord, testis and muscle. Neuroimmunomodulation 1998; 5:36–41.PubMedCrossRefGoogle Scholar
  35. 35.
    Banks, WA, McLay RN, Kastin AJ et al. Passage of leptin across the blood-testis barrier. Am J Physiol 1999; 276:E1099–E1104.PubMedGoogle Scholar
  36. 36.
    King LM, Banks WA, George WJ. Differences in cadmium-transport to the testis, epididymis and brain in cadmium-sensitive and_-resistant murine strains 129/J and A/J. J Pharm Exp Ther 1999; 289:825–830.Google Scholar
  37. 37.
    King LM, Banks WA, George WJ. Differential zinc transport into testis and brain of cadmium-sensitive and_-resistant murine strains. J Androl 2000; 21:656–663.PubMedGoogle Scholar
  38. 38.
    Plotkin SR, Banks WA, Maness LM et al. Differential transport of rat and human interleukin-1α across the blood-brain and blood-testis barrier in rats. Brain Res 2000; 881:57–61.PubMedCrossRefGoogle Scholar
  39. 39.
    Mizushima H, Nakamura Y, Matsumoto H et al. The effect of cardiac arrest on the blood-testis barrier to albumin, tumor necrosis factor alpha, pituitary adenylate cyclase activating polypeptide, sucrose and verapamil in the mouse. J Androl 2001; 22:255–260.PubMedGoogle Scholar
  40. 40.
    Farghali H, Williams DS, Simplaceanu E et al. An evaluation of the integrity of the blood-testis barrier by magnetic resonance imaging. Magnet Reson Med 1991; 22:81–87.CrossRefGoogle Scholar
  41. 41.
    Kim KN, Kim HJ, Lee SD et al. Effect of triolein on the blood-testis barrier in cats. Invest Radiol 2004; 39:445–449.PubMedCrossRefGoogle Scholar
  42. 42.
    Setchell BP. The secretion of fluid by the testis of rats, rams and goats with some observation on the effects of age, cryptorchidism and hypophysectomy. J Reprod Fertil 1970; 23:79–85.PubMedCrossRefGoogle Scholar
  43. 43.
    Russell LD, Bartke A, Goh JC. Postnatal development of the Sertoli cell barrier, tubular lumen, and cytoskeleton of Sertoli and myoid cells in the rat, and their relationship to tubular fluid secretion and flow. Am J Anat 1989; 184:179–189.PubMedCrossRefGoogle Scholar
  44. 44.
    Hinton BT, Setchell BP. Fluid secretion and movement. In: Russell LD, Griswold MD, eds. The Sertoli Cell. Clearwater: Cache River Press, 1993;249–267.Google Scholar
  45. 45.
    Janecki A, Jakubowiak A, Steinberger A. Regulation of transepithelial electrical resistance in two-compartment Sertoli cell cultures: In vitro model of the blood-testis barrier. Endocrinology 1991; 129:1489–1496.PubMedCrossRefGoogle Scholar
  46. 46.
    Djakiew D, Onoda M. Mutichamber cell culture and directional secretion. In: Russell LD, Griswold MD, eds. The Sertoli Cell. Clearwater: Cache River Press, 1993:181–194.Google Scholar
  47. 47.
    Lui WY, Lee WM. CAMP perturbs inter-Sertoli tight junction permeability barrier in vitro via its effect on proteasome-sensitive ubiquination of occludin. J Cell Physiol 2005; 203:564–572.PubMedCrossRefGoogle Scholar
  48. 48.
    Mruk DD, Cheng CY. Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocrin Rev 2004; 25:747–806.CrossRefGoogle Scholar
  49. 49.
    Bawa SR. Fine structure of the Sertoli cell in the human testis. J Ultrastruc Res 1963; 9:459–474.CrossRefGoogle Scholar
  50. 50.
    Brokelmann J. Fine structure of germ cells and Sertoli cells during the cycle of the seminiferous epithelium in the rat. Z Zellforsch Mikrosk Anat 1963; 59:820–850.PubMedCrossRefGoogle Scholar
  51. 51.
    Flickinger C, Fawcett DW. The junctional specializations of Sertoli cells in the seminiferous epithelium. Anat Rec 1967; 158:207–222.PubMedCrossRefGoogle Scholar
  52. 52.
    Nicander L. An electron microscopical study of cell contacts in the seminiferous tubules of some mammals. Z Zellforsch Mikrosk Anat 1967; 83:375–397.PubMedCrossRefGoogle Scholar
  53. 53.
    Ross MH. The Sertoli cell and the blood-testicular barrier: An electronmicroscopic study. In: Holstein AF, Horstmann E, eds. Morphological Aspects of Andrology. Grosse, Berlin: 1970:83–86.Google Scholar
  54. 54.
    Fawcett DW, Leak LV, Heidger PM. Electron microscopic observations on the structural components of the blood-testis barrier. J Reprod Fertil 1970; (Suppl 10):105–122.Google Scholar
  55. 55.
    Dym M, Fawcett DW. The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium. Biol Reprod 1970; 3:308–326.PubMedGoogle Scholar
  56. 56.
    Dym M. The fine structure of the monkey (Macaca) Sertoli cell and its role in maintaining the blood-testis barrier. Anat Rec 1973; 175:639–656.PubMedCrossRefGoogle Scholar
  57. 57.
    Russell LD. The blood-testis barrier and its formation relative to spermatocyte maturation in the adult rat: A lanthanum tracer study. Anat Rec 1978; 190:99–112.PubMedCrossRefGoogle Scholar
  58. 58.
    Pelletier RM, Byers SW. The blood-testis barrier and Sertoli cell junctions: Structural considerations. Microsc Res Tech 1992; 20:3–33.PubMedCrossRefGoogle Scholar
  59. 59.
    Setchell BP, Breed WG. Anatomy, vasculature and innervation of the male reproductive tract. In: Neill JD, ed. Knobil and Neill’s Physiology of Reproduction. 3rd ed. Amsterdam: Elsevier, 2006:771–825.Google Scholar
  60. 60.
    Regaud C. Etudes sur la structure des tubes seminiferes et sur la spermatogenesis chez les mammiferes. Arch Anat Microscop 1901; 4:101–154, 231–380.Google Scholar
  61. 61.
    Ross MH. The fine structure and development of the peritubular contractile cell component in the seminiferous tubules of the mouse. Am J Anat 1967; 121:523–558.PubMedCrossRefGoogle Scholar
  62. 62.
    Palombi F, Farini D, Salanova M et al. Development and cytodifferentiation of peritubular myoid cells in the rat testis. Anat Rec 1992; 233:32–40.PubMedCrossRefGoogle Scholar
  63. 63.
    Fillipini A, Tripiciano A, Palombi F et al. Rat testicular myoid cells respond to endothelin: Characterization of binding and signal transduction pathway. Endocrinology 1993; 133:1789–1796.CrossRefGoogle Scholar
  64. 64.
    Tripiciano A, Fillipini A, Guistiniano Q et al. Direct visualization of rat peritubular myoid cell contraction in response to endothelin. Biol Reprod 1996; 55:25–31.PubMedCrossRefGoogle Scholar
  65. 65.
    Fantoni G, Morris PL, Firti G et al. A new autocrine/paracrine factor in rat testis. Am J Physiol 1993; 265:E267–E274.PubMedGoogle Scholar
  66. 66.
    Norton JN, Skinner MK. Regulation of Sertoli cell function and differentiation through the actions of a testicular paracrine factor P-Mod-S. Endocrinology 1989; 124:2711–2719.PubMedCrossRefGoogle Scholar
  67. 67.
    Skinner MK. Cell-cell interaction in the testis. Endocrin Rev 1991; 12:45–77.CrossRefGoogle Scholar
  68. 68.
    Kurlandsky SB, Gamble MV, Ramakrishnan R et al. Plasma delivery of retinoic acid to tissues in the rat. J Biol Chem 1995; 270:17850–17857.PubMedCrossRefGoogle Scholar
  69. 69.
    Vernet N, Dennefeld C, Rochette-Egly C et al. Retinoic acid metabolism and signaling pathways in the adult and developing mouse testis. Endocrinology 2006; 147:96–110.PubMedCrossRefGoogle Scholar
  70. 70.
    van Pelt AMM, de Rooij DG. Retinoic acid is able to reinitiate spermatogenesis in Vitamin A-deficient rats and high replicate doses support the full development of spermatogenic cells. Endocrinology 1991; 128:697–704.PubMedCrossRefGoogle Scholar
  71. 71.
    Davis JT, Ong DE. Retinol processing by the peritubular cell from rat testis. Biol Reprod 1995; 52:356–364.PubMedCrossRefGoogle Scholar
  72. 72.
    Livera G, Rouiller V, Pairault C et al. Regulation and perturbation of testicular functions by vitamin A. Reproduction 2002; 124:173–180.PubMedCrossRefGoogle Scholar
  73. 73.
    Fawcett DW. Observations on the organization of the interstitial tissue of the testis and on the occluding junctions in the seminiferous epithelium. Adv Biosci 1973; 10:83–99.PubMedGoogle Scholar
  74. 74.
    Duarte HE, de Oliviera C, Orsi AM et al. Ultrastuctural characteristics of the testicular capillaries in the dog (Canis familiaris). Anat Histol Embryol 1995; 24:73–76.PubMedCrossRefGoogle Scholar
  75. 75.
    Pinart E, Bonet S, Briz MD et al. Morphologic and histochemical study of blood capillaries in boar testes: Effects of abdominal cryptorchidism. Teratology 2001; 63:42–51.PubMedCrossRefGoogle Scholar
  76. 76.
    Takayama H. Ultrastructure of testicular capillaries as a permeability barrier (in Japanese). Nippon Hinyokika Gakkai Zasshi 1986; 77:1840–1850.PubMedGoogle Scholar
  77. 77.
    Ergun S, Davidoff M, Holstein AF. Capillaries in the lamina propria of human seminiferous tubules are partly fenestrated. Cell Tissue Res 1996; 286:93–102.PubMedCrossRefGoogle Scholar
  78. 78.
    Stewart PA. Endothelial vesicles in the blood-brain barrier; are they related to permeability? Cell Mol Neurobiol 2000; 20:149–163.PubMedCrossRefGoogle Scholar
  79. 79.
    Moroi S, Saitou M, Fujimoto K et al. Occludin is concentrated at tight junctions of mouse/rat but not human/guinea pig Sertoli cells in testes. Am J Physiol 1998; 274:C1708–C1717.PubMedGoogle Scholar
  80. 80.
    Saitou M, Furuse M, Sasaki H et al. Complex phenotype of mice lacking occludin, a complex of tight junction strands. Mol Biol Cell 2000; 11:4131–4142.PubMedGoogle Scholar
  81. 81.
    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; 140:3815–3825.PubMedCrossRefGoogle Scholar
  82. 82.
    Chung NPY, Mruk D, Mo MY et al. A 22-amino acid synthetic peptide corresponding to the second extracellular loop of rat occludin perturbs the blood-testis barrier and disrupts spermatogenesis reversibly in vivo. Biol Reprod 2001; 65:1340–1351.PubMedCrossRefGoogle Scholar
  83. 83.
    Turksen K, Troy TC. Barriers built on claudins. J Cell Sci 2004; 117:2435–2447.PubMedCrossRefGoogle Scholar
  84. 84.
    Hellani A, Ji J, Mauduit C et al. Developmental and hormonal regulation of the expression of oligodendocyte-specific protein/claudin 11 in mouse testis. Endocrinology 2000; 141:3012–3019.PubMedCrossRefGoogle Scholar
  85. 85.
    Gow A, Southwood CM, Li JS et al. CNS myelin and Sertoli cell tight junction strands are absent in Osp/Claudin-11 null mice. Cell 1999; 99:649–659.PubMedCrossRefGoogle Scholar
  86. 86.
    Morita K, Sasaki H, Furuse M et al. Endothelial claudin: Claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 1999; 147:185–194.PubMedCrossRefGoogle Scholar
  87. 87.
    Kamimura Y, Chiba H, Utsumi H et al. Barrier function of microvessels and roles of glial cell line-derived neurotrophic factor in the rat testis. Med Electron Microsc 2002; 35:139–145.PubMedCrossRefGoogle Scholar
  88. 88.
    Nitta T, Hata M, Gotoh S et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 2003; 161:653–660.PubMedCrossRefGoogle Scholar
  89. 89.
    Salanova M, Stefanini M, De Curtis I et al. Integrin receptor α6 β1 is localized at specific sites of cell-cell contact in rat seminiferous epithelium. Biol Reprod 1995; 52:79–87.PubMedCrossRefGoogle Scholar
  90. 90.
    Salanova M, Ricci G, Boitani C et al. Junctional contacts between Sertoli cells in normal and aspermatogenic rat seminiferous epithelium contain α6 β1 integrins, and their formation is controlled by follicle stimulating hormone. Biol Reprod 1998; 58:371–378.PubMedCrossRefGoogle Scholar
  91. 91.
    Kissel K, Hamm S, Schulz M et al. Immunohistochemical localization of the murine transferrin receptor (TfR) on blood-tissue barriers using a novel anti-TfR monoclonal antibody. Histochem Cell Biol 1998; 10:63–72.CrossRefGoogle Scholar
  92. 92.
    Sylvester SR, Griswold MD. Molecular biology of iron transport in the testis. In: de Kretser DM, ed. Molecular Biology of the Male Reproductive System. San Diego: Academic Press, 1993:311–326.Google Scholar
  93. 93.
    Sylvester SR, Griswold MD. The testicular iron shuttle: A “nurse” function of the Sertoli cells. J Androl 1994; 15:381–385.PubMedGoogle Scholar
  94. 94.
    Onada M, Suarez-Quian CA, Djakiew D et al. Characterization of Sertoli cells cultures in the bicameral chamber system: Relationship between formation of permeability barriers and polarized secretion of transferrin. Biol Repord 1990; 43:672–683.CrossRefGoogle Scholar
  95. 95.
    Djakiew D, Hadley MA, Byers SW et al. Tranferrin-mediated transcellular transport of 59Fe across confluent epithelial sheets of Sertoli cells grown in bicameral cell culture chambers. J Androl 1986; 7:355–366.PubMedGoogle Scholar
  96. 96.
    Sylvester SR, Griswold MD. Localization of transferrin and transferrin receptors in rat testes. Biol Reprod 1984; 31:196–203.Google Scholar
  97. 97.
    Hoyes KP, Johnson C, Johnston RE et al. Testicular toxicity of the transferrin binding radionuclide 114mIn in adult and neonatal rats. Reprod Toxicol 1995; 9:297–305.PubMedCrossRefGoogle Scholar
  98. 98.
    Hoyes KP, Morris ID, Hendry JH et al. Transferrin-mediated uptake of radionuclides by the testis. J Nucl Med 1996; 37:336–340.PubMedGoogle Scholar
  99. 99.
    Hoyes KP, Bingham D, Hendry JH et al. Transferrin-mediated uptake of plutonium by spermatogenic tubules. Int J Radiat Biol 1996; 70:467–471.PubMedCrossRefGoogle Scholar
  100. 100.
    Suire S, Fontaine I, Guillou F. Transferrin gene expression and secretion in rat Sertoli cells. Mol Reprod Dev 1997; 48:168–175.PubMedCrossRefGoogle Scholar
  101. 101.
    Roberts KP, Awonyi CA, Santulli et al. Regulation of Sertoli cell transferrin and sulfated glycoprotein-2 messenger ribonucleic acid levels during restoration of spermatogenesis in the adult hypophysectomized rat. Endocrinology 1991; 129:3417–3423.PubMedCrossRefGoogle Scholar
  102. 102.
    Suire S, Fontaine I, Guillou F. Follicle stimulating hormone (FSH) stimulates transferrin gene transcription in rat Sertoli cells: Cis and trans-acting elements involved in FSH action via cyclic adenosine 3′,5′-monophosphate on the transferrin gene. Mol Endocrinol 1995; 9:756–766.PubMedCrossRefGoogle Scholar
  103. 103.
    Hoeben E, van Damme J, Put W et al. Cytokines derived from activated human mononuclear cells markedly stimulate transferrin secretion by cultured Sertoli cells. Endocrinology 1996; 137:514–521.PubMedCrossRefGoogle Scholar
  104. 104.
    Norton JN, Vigne JL, Skinner MK. regulation of Sertoli cell differentiation by the testicular paracrine factor PmodS: Analysis of common signal transduction pathways. Endocrinology 1994; 134:149–157.PubMedCrossRefGoogle Scholar
  105. 105.
    Hoeben E, Swinnen JV, Heyns W et al. Heregulins or neu differentiation factors and the interactions between peritubular myoid cells and Sertoli cells. Endocrinology 1999; 140:2216–2223.PubMedCrossRefGoogle Scholar
  106. 106.
    Roberts KP, Santulli R, Seiden J et al. The effect of testosterone withdrawal and subsequent germ cell depletion on transferrin and sulfated glycoprotein-2 messenger ribonucleic acid levels in the adult rat testis. Biol Reprod 1992; 47:92–96.PubMedCrossRefGoogle Scholar
  107. 107.
    Maguire SM, Millar MR, Sharpe RM et al. Investigation of the potential role of the germ cell complement in control of the expression of transferrin mRNA in the prepubertal and adult rat testis. J Mol Endocrinol 1997; 19:67–77.PubMedCrossRefGoogle Scholar
  108. 108.
    Skinner MK, Griswold MD. Sertoli cells synthesize and secrete a ceruloplasmin-like protein. Biol Reprod 1983; 28: 1225–1229.PubMedCrossRefGoogle Scholar
  109. 109.
    Augustine LM, Markelewicz RJ, Boekelheide K et al. Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier. Drug Metab Dispos 2005; 33:182–189.PubMedCrossRefGoogle Scholar
  110. 110.
    Griffin KP, Ward DT, Liu W et al. Differential expression of divalent metal transporter DMT1 (Slc11a2) in the spermatogenic epithelium of the developing and adult rat testis. Am J Physiol 2005; C176–C184.Google Scholar
  111. 111.
    Schinkel AH. The physiological function of drug-transporting P-glycoproteins. Sem Cancer Biol 1997; 8:161–170.CrossRefGoogle Scholar
  112. 112.
    Schinkel AH, Jonker JW. Mammalian drug efflux transporter of the ATP binding cassette (ABC) family: An overview. Adv Drug Del Rev 2003; 55:3–29.CrossRefGoogle Scholar
  113. 113.
    Fromm MF. Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci 2004; 25:423–429.PubMedCrossRefGoogle Scholar
  114. 114.
    Leslie EM, Deeley RG, Cole SPC. Multidrug resistance proteins: Role of P-glycoprotein, MRP1, MRP2 and BRCP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 2005; 204:216–237.PubMedCrossRefGoogle Scholar
  115. 115.
    Cordon-Cardo C, O’Brien JP, Casals L et al. Multidrug-resistancce gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci USA 1989; 86:695–698.PubMedCrossRefGoogle Scholar
  116. 116.
    Cordon-Cardo C, O’Brien JP, Boccia J et al. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem 1990; 38:1277–1287.PubMedGoogle Scholar
  117. 117.
    Thiebaut F, Tsuruo T, Hamda H et al. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: Evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J Histochem Cytochem 1989; 37:159–164.PubMedGoogle Scholar
  118. 118.
    Holash JA, Harik SI, Perry G et al. Barrier properties of testis microvessels. Proc Natl Acad Sci USA 1993; 90:11069–11073.PubMedCrossRefGoogle Scholar
  119. 119.
    Melaine N, Lienard MO, Dorval I et al. Multidrug resistance genes and p-glycoprotein in the testis of the rat, mouse, guinea pig and human. Biol Reprod 2002; 67:1699–1707.PubMedCrossRefGoogle Scholar
  120. 120.
    Bart J, Hollema H, Groen HJM et al. The distribution of drug-efflux pumps, Pgp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours. Eur J Cancer 2004; 40:2064–2070.PubMedCrossRefGoogle Scholar
  121. 121.
    Trezise AEO, Romano PR, Gill DR et al. The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression. EMBO J 1992; 11:4291–4303.PubMedGoogle Scholar
  122. 122.
    Stewart PA, Beliveau R, Rogers KA. Cellular localization of P-glycoprotein in brain versus gonadal capillaries. J Histochem Cytochem 1996; 44:679–685.PubMedGoogle Scholar
  123. 123.
    Schinkel AH, Smit JJM, van Tellingen O. Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 77:491–502.PubMedCrossRefGoogle Scholar
  124. 124.
    Schinkel AH, Wagenaar E, van Deemter L et al. Absence of the mdrla P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin and cyclosporin A. J Clin Invest 1995; 96:1698–1705.PubMedCrossRefGoogle Scholar
  125. 125.
    Schinkel AH, Wagenaar E, Mol CAAM et al. P-Glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996; 97:2517–2524.PubMedCrossRefGoogle Scholar
  126. 126.
    Van Asperen J, Schinkel AH, Beijenen JH et al. Altered pharmacokinetics of vinblastine in mdr la P-glycoprotein deficient mice. J Natl Cancer Inst 1996; 88:994–999.PubMedCrossRefGoogle Scholar
  127. 127.
    Uhr M, Steckler T, Yassouridis A et al. Penetration of amitriptyline, but not of fluoxetine into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology. 2000; 22:380–387.PubMedCrossRefGoogle Scholar
  128. 128.
    Grauer MT, Uhr M. P-glycoprotein reduces the ability of amitriptyline metabolites to cross the blood-brain barrier in mice after a 10-day administration of amitriptyline. J Psychopharmacol 2004; 18:66–74.PubMedCrossRefGoogle Scholar
  129. 129.
    Uhr M, Ebinger M, Rosenhagen MC et al. The anti-Parkinson drug budipine is exported actively out of the brain by P-glycoprotein in mice. Neurosci Lett 2005; 383:73–76.PubMedCrossRefGoogle Scholar
  130. 130.
    Uhr M, Holsboer F, Muller MB. Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone and progesterone into the brain is enhanced in mice deficient for both mdrla and mdrlb P-glycoproteins. J Neuroendocrinol 2002; 14:753–759.PubMedCrossRefGoogle Scholar
  131. 131.
    Karssen AM, Meijer OC, van der Sandt ICJ et al. Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain. Endocrinology 2001; 142:2686–2694.PubMedCrossRefGoogle Scholar
  132. 132.
    Karssen AM, Meijer OC, van der Sandt ICJ et al. The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone. J Endocrinol 2002; 175:251–260.PubMedCrossRefGoogle Scholar
  133. 133.
    Huisman MT, Smit JW, Schinkel AH. Significance of P-glycoprotein for the pharmacology and clinical use of HIV protease inhibitors. AIDS 2000; 14:237–242.PubMedCrossRefGoogle Scholar
  134. 134.
    Choo EF, Leake B, Wandel C et al. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testis. Drug Metab Dispos 2000; 28:655–660.PubMedGoogle Scholar
  135. 135.
    Huisman MT, Smit JW, Wiltshire HR et al. Assessing safety and efficacy of directed P-glycoprotein inhibition to improve the pharmacokinetic properties of saquinavir coadministered with ritonavir. J Pharmacol Exp Ther 2003; 304:596–602.PubMedCrossRefGoogle Scholar
  136. 136.
    Arboix M, Paz OG, Colombo T et al. Mutidrug resistance-reversing agents increase vinblastine distribution in normal tissues expressing the P-glycoprotein but do not enhance drug penetration into brain and testis. J Pharmacol Exp Ther 1997; 281: 1226–1230.PubMedGoogle Scholar
  137. 137.
    Forrest JB, Turner TT, Howard SS. Cyclophosphamide, vincristine and the blood-testis barrier. Invest Urol 1981; 18:443–444.PubMedGoogle Scholar
  138. 138.
    Trezise AEO, Buchwald M. In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator. Nature 1991; 353:434–437.PubMedCrossRefGoogle Scholar
  139. 139.
    Stride BD, Valdimarsson G, Gerlach JH et al. Structure and expression of the messenger RNA encoding the murine multidrug resistance protein, an ATP cassette transporter. Mol Pharmacol 1996; 49:962–971.PubMedGoogle Scholar
  140. 140.
    Flens MJ, Zaman GJR, van der Valk P et al. Tissue distribution of the multidrug resistance protein. Am J Path 1996; 148:1237–1247.PubMedGoogle Scholar
  141. 141.
    Wijnholds J, Scheffer GL, van der Valk M et al. Mutidrug resistance protein 1 protects the oropharanygeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 1998; 188:797–808.PubMedCrossRefGoogle Scholar
  142. 142.
    Tribull TE, Bruner RH, Bain LJ. The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol Lett 2003; 142:61–70.PubMedCrossRefGoogle Scholar
  143. 143.
    Qian YM, Song WC, Cui H et al. Glutathione stimulated sulfated estrogen transport by multidrug resistance protein 1. J Biol Chem 2001; 276:6404–6411.PubMedCrossRefGoogle Scholar
  144. 144.
    Borst P, Oude Elferink R. Mammalian ABC transporter in health and disease. Ann Rev Biochem 2002; 71:537–592.PubMedCrossRefGoogle Scholar
  145. 145.
    Riccardi, R, Vigersky RA, Barnes S et al. Methotrexate in the interstitial space and seminiferous tubules of rat testis. Cancer Res 1982; 42:1617–1619.PubMedGoogle Scholar
  146. 146.
    Niemi M, Setchell BP. Gamma glutamyl transpeptidase in the vasculature of the rat testis. Biol Reprod 1986; 35:385–391.PubMedCrossRefGoogle Scholar
  147. 147.
    Bustamante JC, Setchell BP. The uptake of amino acids, in particular leucine, by isolated perfused testes of rats. J Androl 2000; 21:452–463.PubMedGoogle Scholar
  148. 148.
    Duelli R, Enerson BE, Gerhardt DZ et al. Expression of large amino acid transporter LAT1 in rat brain endothelium. J Cereb Blood Flow Metab 2000; 20:1557–1562.PubMedCrossRefGoogle Scholar
  149. 149.
    Ghabriel MN, Lu JJ, Hermanis G et al. Expression of a blood-brain barrier specific antigen in the male reproductive tract. Reproduction 2002; 123:389–397.PubMedCrossRefGoogle Scholar
  150. 150.
    Fenton RA, Howorth A, Cooper GJ et al. Molecular characterization of a novel UT-A urea transporter isoform (UT-A5) in testis. Am J Physiol 2000; 279:C1425–C1431.Google Scholar
  151. 151.
    Fenton RA, Cooper GJ, Morris ID et al. Coordiated expression of UT-A and UT-B urea transporters in rat testis. Am J Physiol 2002; 282:C1492–C1501.Google Scholar
  152. 152.
    Turner TT, Hartmann PK, Howards SS. Urea in the seminiferous tubule: Evidence for active transport. Biol Reprod 1979; 20:511–515.PubMedCrossRefGoogle Scholar
  153. 153.
    Kato R, Maeda T, Akaike T et al. Nucleoside transport at the blood-testis barrier studied with primary-cultured Sertoli cells. J Pharmacol Exp Ther 2005; 312:601–608.PubMedCrossRefGoogle Scholar
  154. 154.
    Ong DE, Chytil F. Retinoic acid-binding protein in rat tissue. J Biol Vhem 1975; 250:6113–6117.Google Scholar
  155. 155.
    Kato M, Sung WK, Kato K et al. Immunohistochemical studies on the localization of cellular retinol-binding protein in rat testis and epididymis. Biol Reprod 1985; 32:173–189.PubMedCrossRefGoogle Scholar
  156. 156.
    Davis JT, Ong DE. Synthesis and secretion of retinal-binding protein by cultured rat Sertoli cells. Biol Reprod 1992; 47:528–533.PubMedCrossRefGoogle Scholar
  157. 157.
    Rajan N, Sung WK, Goodman DS. Localization of cellular retinol-binding protein mRNA in rat testis and epididymis and its stage-dependent expression during the cycle of the seminiferous epithelium. Biol Reprod 1990; 43:835–842.PubMedCrossRefGoogle Scholar
  158. 158.
    McGuire BW, Orgebin-Crist MC, Chytil F Autoradiographic localization of serum retinal-binding protein in rat testis. Endocrinology 1981; 108:658–667.PubMedCrossRefGoogle Scholar
  159. 159.
    Rajguru SU, Kang YH, Ahluwalia BS. Localization of retinol (Vitamin A) in rat testes. J Nutr 1982; 112:1881–1891.PubMedGoogle Scholar
  160. 160.
    Shingleton JL, Skinner MK, Ong DE. Characteristics of retinol accumulation from serum retinal-binding protein by cultured Sertoli cells. Biochemistry 1989; 28:9641–9647.PubMedCrossRefGoogle Scholar
  161. 161.
    Samy ET, Li JCH, Grima J et al. Sertoli cell prostaglandin D2 synthetase is a multifunctional molecule: Its expression and regulation. Endocrinology 2000; 141:710–721.PubMedCrossRefGoogle Scholar
  162. 162.
    Gerena RL, Irikura D, Urade Y et al. Identification of a fertility-associated protein in bull seminal plasma as lipocalin-type prostaglandin D synthase. Biol Reprod 1998; 58:826–833.PubMedCrossRefGoogle Scholar
  163. 163.
    Vitale R, Fawcett DW, Dym M. The normal development of the blood-testis barrier and the effects of clomiphene and estrogen treatment. Anat Rec 1973; 176:333–344.CrossRefGoogle Scholar
  164. 164.
    Gilula NB, Fawcett DW, Aoki A. The Sertoli cell occluding junctions and gap junctions in mature and developing mammalian testis. Dev Biol 1976; 50:142–168PubMedCrossRefGoogle Scholar
  165. 165.
    Pelletier RM, Friend DS. The Sertoli cell junctional complex: structure and permeability to filipin in the neonatal and adult guinea pig. Am J Anat 1983; 168:213–228.PubMedCrossRefGoogle Scholar
  166. 166.
    Nagano T, Suzuki F. The postnatal development of the junctional complexes of the mouse Sertoli cells as revealed by freeze-fracture. Anat Rec 1976; 185:403–418.PubMedCrossRefGoogle Scholar
  167. 167.
    Bergmann M, Dierichs R. Postnatal formation of the blood-testis barrier in the rat with special reference to the initiation of meiosis. Anat Embryol 1983; 168:269–275.PubMedCrossRefGoogle Scholar
  168. 168.
    Pelletier RM. Cyclic formation and decay of the blood-testis barrier in the mink (Mustela vison), a seasonal breeder. Am J Anat 1986; 175:91–117.PubMedCrossRefGoogle Scholar
  169. 169.
    Pelletier RM. Blood barriers of the epididymis and vas deferens act asynchronously with the blood barrier of the testis in the mink (Mustela vison). Microsc Res Tech 1994; 27:333–349.PubMedCrossRefGoogle Scholar
  170. 170.
    Morales A, Cavicchia JC. Seasonal changes of the blood-testis barrier in viscacha (Lagostomus maximus maximus): A freeze-fracture and lanthanum tracer study. Anat Rec 1993; 236:459–464.PubMedCrossRefGoogle Scholar
  171. 171.
    Bergmann M. Photoperiod and testicular function in Phodopus sungorus. Adv Anat Embryol Cell Biol 1987; 105:1–76.PubMedGoogle Scholar
  172. 172.
    Levy S, Serre V, Hermo L et al. The effects of aging on the seminiferous epithelium and the blood-testis barrier of the Brown Norway rat. J Androl 1999; 20:356–365.PubMedGoogle Scholar
  173. 173.
    Toyama Y, Ohkawa M, Oku R et al. Neonatally administered diethylstilbestrol retards the development of the blood-testis barrier in the rat. J Androl 2001; 22:413–423.PubMedGoogle Scholar
  174. 174.
    Hosoi I, Toyama Y, Maekawa M et al. Development of the blood-testis barrier in the mouse is delayed by neonatally administered diethylstilbestrol but not by ß-estradiol 3-benzoate. Andrologia 2002; 34:255–262.PubMedCrossRefGoogle Scholar
  175. 175.
    Janecki A, Jakubowiak A, Steinberger A. Effects of cyclic AMP and phorbol ester on transepithelial electrical resistance of Sertoli cell monolayers in two-compartment culture. Mol Cell Endocrinol 1991; 82:61–69.PubMedCrossRefGoogle Scholar
  176. 176.
    Xia W, Cheng CY. TGF-β3 regulates anchoring junction dynamics in the seminiferous epithelium of the rat testis via the Ras/ERK signaling pathway: An in vivo study. Dev Biol 2005; 280:321–343.PubMedCrossRefGoogle Scholar
  177. 177.
    Li MWM, Xia W, Mruk DD et al. Tumor necrosis factor α reversibly disrupts the blood-testis barrier and impairs Sertoli-germ cell adhesion in the seminiferous epithelium of adult rat testes J Endocrinol 2006; 190:313–329.PubMedCrossRefGoogle Scholar
  178. 178.
    Kerr JB, Savage GN, Millar M et al. Response of the seminiferous epithelium of the rat testis to withdrawal of androgen; evidence for direct effect upon intercellular spaces associated with Sertoli cell junctional complexes. Cell Tissue Res 1993; 274:153–161.PubMedCrossRefGoogle Scholar
  179. 179.
    Gye MC, Ohsako S. Effects of flutamide in the rat testis on the expression of occludin, an integral member of the tight junctions. Toxicol Lett 2003; 143:217–222.PubMedCrossRefGoogle Scholar
  180. 180.
    Xia W, Wong CH, Lee NP et al. Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood-testis barrier integrity: An in vivo study using an androgen suppression model. J Cell Physiol 2005; 205:141–157.PubMedCrossRefGoogle Scholar
  181. 181.
    Cavicchia JC, Sacerdote FL. Correlation between blood-testis barrier development and onset of the first spermatogenic wave in normal and busulfan-treated rats; a lanthanum and freeze-fracture study. Anat Rec 1991; 230:361–368.PubMedCrossRefGoogle Scholar
  182. 182.
    Ribiero AF, David-Ferreira JF. The inter-Sertoli cell tight junctions in germ cell-free seminiferous tubules from prenatally irradiated rats: A freeze-fracture study. Cell Biol Int 1996; 20:513–522.CrossRefGoogle Scholar
  183. 183.
    Levine N, Marsh DJ. Micropuncture study of the fluid composition of “Sertoli cell-only” seminiferous tubules in rats. J Reprod Fertil 1975; 43:547–549.PubMedCrossRefGoogle Scholar
  184. 184.
    Huang HFS, Yang CS, Meyenhofer M et al. Disruption of sustentacular (Sertoli) cell tight junctions and regression of spermatogenesis in vitamin-A-deficient rats. Acta Anat 1988; 133:10–15.PubMedCrossRefGoogle Scholar
  185. 185.
    Ismail N, Morales CR. Effects of vitamin A deficiency on the inter-Sertoli cell tight junctions and on the germ cell population. Microsc Res Tech 1992; 20:43–49.PubMedCrossRefGoogle Scholar
  186. 186.
    Morales A, Cavicchia JC. Spermatogenesis and blood-testis barrier in rats after long-term vitamin A deprivation. Tissue Cell 2002; 34:349–355.PubMedCrossRefGoogle Scholar
  187. 187.
    Setchell BP. The movement of fluids and substances in the testis. Aust J Biol Sci 1986; 39:193–207.PubMedGoogle Scholar
  188. 188.
    Neaves WB. Permeability of Sertoli cell tight junctions to lanthanum after ligation of ductus deferens and ductuli efferentes. J Cell Biol 1973; 59:559–572.PubMedCrossRefGoogle Scholar
  189. 189.
    Ross MH. Permeability of Sertoli-Sertoli junctions and Sertoli-spermatid junctions after efferent duct ligation and lanthanum treatment. Am J Anat 1977; 148:49–56.PubMedCrossRefGoogle Scholar
  190. 190.
    Osman DI, Ploen L. The terminal segment of the seminiferous tubules and the blood-testis barrier before and after efferent duct ligation in the rat. Int J Androl 1978; 1:235–249.CrossRefGoogle Scholar
  191. 191.
    Anton E. Preservation of the rat blood-testis barrier after ligation of the ductuli efferentes, as demonstrated by intra-arterial perfusion with peroxidase. J Reprod Fertil 1982; 66:227–230.PubMedCrossRefGoogle Scholar
  192. 192.
    Porsti I, Ylitalo P. Penetration of some compounds through blood-brain and blood-testis barriers in chronically hypertensive rats. Acta Physiol Scand 1984; 120:387–391.PubMedCrossRefGoogle Scholar
  193. 193.
    Gravis CJ, Chen I, Yates RD. Stability of the intra-epithelial component of the blood-testis barrier in epinephrine-induced testicular degeneration in Syrian hamsters. Am J Anat 1977; 148:19–32.PubMedCrossRefGoogle Scholar
  194. 194.
    Setchell BP, Waites GMH. Changes in the permeability of testicular capillaries and of the “blood-testis barrier” after injection of cadmium chloride in the rat. J Endocrinol 1970; 41: 81–86.CrossRefGoogle Scholar
  195. 195.
    Johnson MH. The effect of cadmium chloride on the blood-testis barrier of the guinea-pig. J Reprod Fertil 1969; 551–553.Google Scholar
  196. 196.
    Lee IP, Dixon RL. Effects of cadmium on spermatogenesis studied by velocity sedimentation cell separation and serial mating. J Pharmacol Exp Ther 1973; 187:641–652.PubMedGoogle Scholar
  197. 197.
    Janecki A, Jakubowiak A, Steinberger A. Effect of cadmium chloride on transepithelial electrical resistance of Sertoli cell monolayers in two-compartment cultures—A new model for toxicological investigations of the “blood-testis” barrier in vitro. Toxicol Appl Pharmacol 1992; 112:51–57.PubMedCrossRefGoogle Scholar
  198. 198.
    Chung NPY, Cheng CY. Is cadmium chloride-induced inter-Sertoli tight junction permeability barrier disruption a suitable in vitro model to study the events of junction disassembly during spermatogenesis in the rat testis. Endocrinology 2001; 142:1878–1888.PubMedCrossRefGoogle Scholar
  199. 199.
    Hew KW, Heath GL, Jiwa AH et al Cadmium in vivo causes disruption of tight junction-associated microfilaments in rat Sertoli cells. Biol Reprod 1993; 49:840–849.PubMedCrossRefGoogle Scholar
  200. 200.
    Wong CH, Mruk DD, Lui WY et al. Regulation of blood-testis barrier dynamics: An in vivo study. J Cell Sci 2004; 117:783–798.PubMedCrossRefGoogle Scholar
  201. 201.
    Wong CH, Mruk DD, Siu MKY et al. Blood-testis barrrier dynamics are regulated by α-macroglobulin via the c-jun N-terminal protein kinase pathway. Endocrinology 2005; 146:1893–1908.PubMedCrossRefGoogle Scholar
  202. 202.
    Weber JE, Turner TT, Tung KSK et al. Effects of cytochalasin D on the integrity of the Sertoli cell (blood-testis) barrier. Am J Anat 1988; 182:130–147.PubMedCrossRefGoogle Scholar
  203. 203.
    Eng F, Wiebe JP, Alima LH. Long-term alteration in the permeability of the blood-testis barrier following a single intratesticular injection of dilute aqueous glycerol. J Androl 1994; 15:311–317.PubMedGoogle Scholar
  204. 204.
    Wiebe JP, Kowalik A, Gallardi RL et al. Glycerol disrupts tight junction-associated actin microfilaments, occludin, and microtubules in Sertoli cells. J Androl 2000; 21:625–635.PubMedGoogle Scholar
  205. 205.
    Hall ES, Eveleth J, Boekelheide K. 2,5-Hexadione exposure alters the rat Sertoli cell cytoskeleton. II. Intermediate filaments and actin. Toxicol Appl Pharmacol 1991; 111:443–453.PubMedCrossRefGoogle Scholar
  206. 206.
    Pogach LM, Lee Y, Gould S et al. Characterization of cis-platinum-induced Sertoli cell dysfunction in rodents. Toxicol Appl Pharmacol 1989; 98:350–361.PubMedCrossRefGoogle Scholar
  207. 207.
    Pereira ML. Studies on the permeability of the blood-testis barrier in stainless steel-administered mice. Cell Biol Int 1995; 19:619–624.PubMedCrossRefGoogle Scholar
  208. 208.
    Toyama Y, Suzuki-Toyota F, Maekawa M et al. Adverse effects of bisphenol A to spermiogenesis in mice and rats. Arch Histol Cytol 2004; 67:373–381.PubMedCrossRefGoogle Scholar
  209. 209.
    Willson JT, Jones NA, Katxh S et al. Penetration of the testicular-tubular barrier by horseradish peroxidase induced by adjuvant. Anat Rec 1973; 176:85–100.CrossRefGoogle Scholar
  210. 210.
    Main SJ, Waites GMH. The blood-testis barrier and temperature damage to the testis of the rat. J Reprod Fertil 1977; 51:439–450.PubMedCrossRefGoogle Scholar
  211. 211.
    Stewart RJ, Boyd S, Brown S et al. The blood-testis barrier in experimental unilateral cryptorchidism. J Path 1990; 160:51–55.PubMedCrossRefGoogle Scholar
  212. 212.
    Hagenas L, Ploen L, Ritzen EM et al. Blood-testis barrier: Maintained function of inter-Sertoli cell junction in experimental cryptorchidsm in the rat, as judged by a simple lanthanum-immersion technique. Andrologia 1976; 9:3–7.Google Scholar
  213. 213.
    Cavicchia JC, Sacerdote FL, Ortiz L. The human blood-testis barrier in impaired spermatogenesis. Ultrastuct Path 1996; 20:211–218.CrossRefGoogle Scholar
  214. 214.
    Meyer JM, Mezrahid P, Vignon F et al. Sertoli cell barrier dysfunction and spermatogenic breakdown in the human testis: A lanthanum tracer investigation. Int J Androl 1996; 19:190–198.PubMedCrossRefGoogle Scholar
  215. 215.
    Fritz IB, Lyon MF, Setchell BP. Evidence for a defective seminiferous tubule barrier in testes of Tfm and Sxr mice. J Reprod Fertil 1983; 67:359–363.PubMedCrossRefGoogle Scholar
  216. 216.
    Noguchi J, Toyama Y, Yuasa S et al. Hereditary defects in both germ cells and the blood-testis barrier system in as-mutant rats: Evidence from spermatogonial transplantation and tracer permeability analysis. Biol Reprod 2002; 67:880–888.PubMedCrossRefGoogle Scholar
  217. 217.
    Berg KA. The blood-testis barrier in sterile blue fox-silvr fox hybrids compared with that in normal foxes of both species. Int J Androl 1984; 7:167–175.CrossRefGoogle Scholar
  218. 218.
    Setchell BP. The functional significance of the blood-testis barrier. J Androl 1980; 1:2–10.Google Scholar
  219. 219.
    Teuscher C, Wild GC, Tung KSK. Immunochemical analysis of guinea pig sperm autoantigens. Biol Reprod 1982; 26:218–229.PubMedCrossRefGoogle Scholar
  220. 220.
    Tung KSK, Teuscher C. Mechanisms of autoimmune disease in the testis and ovary. Hum Reprod Update 1995; 1:35–50.PubMedCrossRefGoogle Scholar
  221. 221.
    Yule TD, Montoya GD, Russell LD et al. Autoantigenic cells exist outside the blood testis barrier. J Immunol 1988; 141:1161–1167.PubMedGoogle Scholar
  222. 222.
    Lustig L, Satz ML, Sztein MB et al. Antigens of the basement membranes of the seminferous tubules induce autoimmunity in Wistar rats. J Reprod Immunol 1982; 4:79–90.PubMedCrossRefGoogle Scholar
  223. 223.
    Rival C, Guazzone VA, Theas MS et al. Pathomechanism of autoimmune orchitis. Andrologica 2005; 37:226–227.CrossRefGoogle Scholar
  224. 224.
    Yule TD, Tung KSK. Experimental autoimmune orchitis induced by testis and sperm antigen-specific T cell clones: An important pathogenic cytokine in tumor necrosis factor. Endocrinology 1993; 133:1098–1107.PubMedCrossRefGoogle Scholar
  225. 225.
    Maddocks S, Setchell BP. The rejection of thyroid allografts in the ovine testis. Immunol Cell Biol 1988; 66:1–8.PubMedCrossRefGoogle Scholar
  226. 226.
    Setchell BP, Granholm T, Ritzen EM. Failure of thyroid allografts to function in the testes of cynomolgous monkeys. J Reprod Immunol 1995; 28:75–80.PubMedCrossRefGoogle Scholar
  227. 227.
    Hedger M. Immunophysiology of the male reproductive tract. In: Neill JD, ed. Knobil and Neill’s Physiology of Reproduction. 3rd ed. Amsterdam: Elsevier, 2006:1195–1286.Google Scholar
  228. 228.
    Setchell BP, Pakarinen P, Huhtaniemi I. How much LH do the Leydig cells see? J Endocrinol 2002; 175:375–382.PubMedCrossRefGoogle Scholar
  229. 229.
    Lincoln GA. Seasonal aspects of testicular function. In: Burger H, de Krester D, eds. The Testis, 2nd edition. New York: Raven Press, 1989:329–385.Google Scholar
  230. 230.
    Setchell BP, Laurie MS, Main SJ et al. The mechanism of transport of testosterone through the walls of the seminiferous tubules of the rat testis. Int J Androl 1978; (Suppl 2):506–512.Google Scholar
  231. 231.
    Setchell BP, Laurie MS, Flint APF et al. Transport of free and conjugated steroids from the boar testis in lymph, venous blood and rete testis fluid. J Endocrinol 1983; 96:127–136.PubMedCrossRefGoogle Scholar
  232. 232.
    Setchell BP, Cox JE. Secretion of free and conjugated steroids by the horse testis into lymph and venous blood. J Reprod Fertil 1982; (Suppl. 32):123–127.Google Scholar
  233. 233.
    Jutte NH, Jabseb R, Grootegoed JA et al. Regulation of survival of rat pachytene spermatocytes by lactate supply from Sertoli cells. J Reprod Fertil 1982; 65:431–438.PubMedCrossRefGoogle Scholar
  234. 234.
    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; 16:469–493.PubMedCrossRefGoogle Scholar
  235. 235.
    Brinster RL, Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci USA 1994; 91:11298–11302.PubMedCrossRefGoogle Scholar
  236. 236.
    Jahnukainen K, Hou M, Petersen C et al. Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer Res 2001; 61:706–710.PubMedGoogle Scholar
  237. 237.
    Parks JE, Lee DR, Huang S et al. Prospects for spermatogenesis in vitro. Theriogenology 2003; 59:73–86.PubMedCrossRefGoogle Scholar
  238. 238.
    Zhai Y, Sperkova Z, Napoli JL. Cellular expression retinal dehydrogenase types 1 and 2: Effects of Vitamin A status on testis mRNA. J Cell Physiol 2001; 186–232.Google Scholar
  239. 239.
    Bowles J, Knight D, Smith C et al. Retinoid signaling determines germ cell fate in mice. Science 2006; 312:596–600.PubMedCrossRefGoogle Scholar
  240. 240.
    Koubova J, Menke DB, Zhou Q et al. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Nat Acad Sci USA 2006; 103:2474–2479.PubMedCrossRefGoogle Scholar
  241. 241.
    Oulad-Abdelghani M, Bouillet P, Decimo D et al. Characteriation of a premeiotic germ cell-specific cytoplasmic protein encoded by Stra8, a novel retinoic acid-responsive gene. J Cell Biol 1996; 135:469–477.PubMedCrossRefGoogle Scholar
  242. 242.
    Beumer TL, Kiyokawa H, Roepers-Gajadien HL et al. Regulatory role of p27kip 1 in the mouse and human testis. Endocrinology 1999; 140:1834–1840.PubMedCrossRefGoogle Scholar
  243. 243.
    Buzzard JJ, Wreford NG, Morrison JR. Thyroid hormone, retinoic acid and testosterone suppress proliferation and induce markers of differentiation in cultured rat Sertoli cells. Endocrinology 2006; 144:3722–3731.CrossRefGoogle Scholar
  244. 244.
    Akmal KM, Dufour JM, Kim KH. Retinoic acid receptor α gene expression in the rat testis: Potential role during the prophase of meiosis and in the transition from round to elongating spermatids. Biol Reprod 1997; 56:549–556.PubMedCrossRefGoogle Scholar
  245. 245.
    Chung SSW, Wolgemuth DJ. Role of retinoid signaling in the regulation of spermatogenesis. Cytogenet Genome Res 2004; 105:189–202.PubMedCrossRefGoogle Scholar
  246. 246.
    Chung SSW, Sung W, Wang X et al. Retinoic acid receptor α is required for synchronization of spermatogenic cycles and its absence results in progressive breakdown of the spermatogenic process. Dev Dynam 2004; 230:754–766.CrossRefGoogle Scholar
  247. 247.
    Ghyselinck NB, Vernet N, Dennefeld et al. Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinal binding protein. Dev Dynam 2006; 235:1608–1622.CrossRefGoogle Scholar
  248. 248.
    de Rooij DG, van Pelt AMM, Van de Kant HJG et al. Role of retinoids in spermatogonial proliferation and differentiation and the meiotic prophase. In: Bartke A, ed. Function of Somatic Cells in the Testis. New York: Springer Verlag, 1994:345–361.Google Scholar
  249. 249.
    van Pelt AMM, van Dissel-Emiliani FMF, Gaemers IC et al. Characteristics of A spermatogonia and preleptotene spermatocytes in the Vitamin A-deficient rat testis. Biol Reprod 1995; 53:570–578.PubMedCrossRefGoogle Scholar
  250. 250.
    Gaemers IC, Sonneveld E, van Pelt AMM et al. The effect of 9-cis-retinoic acid on proliferation and differentiation of A spermatogonia and retinoid receptor gene expression in the Vitamin A-deficient mouse testis. Endocrinology 1998; 139:4269–4276.PubMedCrossRefGoogle Scholar
  251. 251.
    Setchell BP, Palombi F. Isolation of endothelial cells from the rat testis, and their effect on testosterone secretion by interstitial cells Miniposter 13th European Workshop on Molecular and Celular Endocrinology of the Testis. 2004; C6.Google Scholar
  252. 252.
    Richardson LL, Kleinman HK, Dym M. Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol Reprod 1995; 52:320–330.PubMedCrossRefGoogle Scholar
  253. 253.
    Onoda M, Djakiew D. Pachytene spermatocyte protein(s), stimulate Sertoli cells grown in bicameral chambers: Dose-dependent secretion of ceruloplasmin, sulfated glucoprotein-1, sulfated glycoprotein-2 and transferring. In Vitro Cell Dev Biol 1991; 27A:215–222.PubMedCrossRefGoogle Scholar
  254. 254.
    Onoda M, Djakiew D. A 29,000M ® protein derived from round spermatids regulates Sertoli cell secretion. Mol Cell Endocrinol 1993; 93:53–61.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Brian P. Setchell
    • 1
  1. 1.Department of Anatomical SciencesUniversity of AdelaideAdelaideAustralia

Personalised recommendations