A local autocrine axis in the testes that regulates spermatogenesis

Nature Reviews Endocrinology

Volumn 6, Issue 7, 2010, Pages 380-395

  Cheng, C Yan ^a   Mruk, Dolores D ^a  

^a POPULATION COUNCIL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; GELATINASE A; HORMONE; LAMININ; METALLOPROTEINASE; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE; TESTOSTERONE;

AUTOCRINE EFFECT; BLOOD TESTIS BARRIER; CONTRACEPTION; HEMIDESMOSOME; HUMAN; HYPOTHALAMUS HYPOPHYSIS SYSTEM; NONHUMAN; PRIORITY JOURNAL; REVIEW; SPERMATOCYTE; SPERMATOGENESIS; TESTIS; ANATOMY AND HISTOLOGY; ANIMAL; BIOLOGICAL MODEL; MALE; METABOLISM; PHYSIOLOGY;

ANIMALS; AUTOCRINE COMMUNICATION; BLOOD-TESTIS BARRIER; HUMANS; MALE; MODELS, BIOLOGICAL; SPERMATOGENESIS; TESTIS;

EID: 77954024451     PISSN: 17595029     EISSN: 17595037     Source Type: Journal    
DOI: 10.1038/nrendo.2010.71     Document Type: Review

References (153)

1. Sharpe, R. M. in The Physiology of Reproduction (eds Knobil, E. & Neill, J. D.) 1363-1434 (Raven Press, New York, 1994).
2. Sokol, R. Z. Endocrinology of male infertility: evaluation and treatment. Semin. Reprod. Med. 27, 149-158 (2009).
3. Kakar, S. S., Malik, M. T., Winters, S. J. & Mazhawidza, W. Gonadotropin-releasing hormone receptors: structure, expression, and signaling transduction. Vitam. Horm. 69, 151-207 (2004).
4. Carreau, S., Wolczynski, S. & Galeraud-Denis, i. Aromatase, oestrogens and human reproduction. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1571-1579 (2010).
5. McLachlan, R. i. et al. Hormonal regulation of spermatogenesis in primates and man: insights for development of the male hormonal contraceptive. J. Androl. 23, 149-162 (2002).
6. Mather, J. P., Moore, A. & Li, R. H. Activins, inhibins, and follistatins: further thoughts on a growing family of regulators. Proc. Soc. Exp. Biol. Med. 215, 209-222 (1997).
7. Wang, R. S., Yeh, S., Tzeng, C. R. & Chang, C. Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice. Endocr. Rev. 30, 119-132 (2009).
8. Lyon, M. F. & Hawkes, S. G. X-linked gene for testicular feminization in the mouse. Nature 227, 1217-1219 (1970).
9. De Gendt, K. et al. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc. Natl Acad. Sci. USA 101, 1327-1332 (2004).
10. Chang, C. et al. infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proc. Natl Acad. Sci. USA 101, 6876-6881 (2004).
11. Holdcraft, R. W. & Braun, R. E. Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 131, 459-467 (2004).
12. Welsh, M., Saunders, P. T., Atanassova, N., Sharpe, R. M. & Smith, L. B. Androgen action via testicular peritubular myoid cells is essential for male fertility. FASEB J. 23, 4218-4230 (2009).
13. Abel, M. H. et al. The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction. Endocrinology 141, 1795 - 1803 (2000).
14. Kumar, T. R., Wang, Y., Lu, N. & Matzuk, M. M. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat. Genet. 15, 201-204 (1997). (Pubitemid 27061644)
15. Krishnamurthy, H., Danilovich, N., Morales, C. R. & Sairam, M. R. Qualitative and quantitative decline in spermatogenesis of the folliclestimulating hormone receptor knock-out (FORKO) mouse. Biol. Reprod. 62, 1146-1159 (2000).
16. Abel, M. H. et al. Spermatogenesis and Sertoli cell activity in mice lacking Sertoli cell receptors for follicle-stimulating hormone and androgen. Endocrinology 149, 3279-3285 (2008).
17. de Kretser, D. M. & Kerr, J. B. in The Physiology of Reproduction, vol.1 (eds Knobil, E. & Neill, J.) 837-932 (Raven Press, New York, 1988).
18. Carreau, S. & Hess, R. A. Oestrogens and spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1517-1535 (2010).
19. Carreau, S. Estrogen: Roles in spermatogenesis. Immun. Endocr. Metab. Agents Med. Chem. 8, 59-65 (2008).
20. Shaha, C. in Molecular Mechanisms in Spermatogenesis (ed. Cheng, C. Y.) 42-64 (Landes Bioscience and Springer Science+Business Media, Austin, TX, 2008).
21. Tripathi, R., Mishra, D. P. & Shaha, C. Male germ cell development: turning on the apoptotic pathways. J. Reprod. Immunol. 83, 31-35 (2009).
22. D'Souza, R. et al. Effect of high intratesticular estrogen on the seminiferous epithelium in adult male rats. Mol. Cell. Endocrinol. 241, 41-48 (2005).
23. Pentikainen, v., Erkkila, K., Suomalainen, L., Parvinen, M. & Dunkel, L. Estradiol acts as a germ cell survival factor in the human testis in vitro. J. Clin. Endocrinol. Metab. 85, 2057-2067 (2000).
24. Sirianni, R. et al. The novel estrogen receptor, G protein-coupled receptor 30, mediates the proliferative effects induced by 17beta-estradiol on mouse spermatogonial GC-1 cell line. Endocrinology 149, 5043-5051 (2008).
25. Lie, P. P., Cheng, C. Y. & Mruk, D. D. Coordinating cellular events during spermatogenesis: A biochemical model. Trends Biochem. Sci. 34, 366-373 (2009).
26. Dym, M. Basement membrane regulation of Sertoli cells. Endocr. Rev. 15, 102-115 (1994).
27. Orth, J. M. Proliferation of Sertoli cells in fetal and postnatal rats: a quantitative autoradiographic study. Anat. Rec. 203, 485-492 (1982).
28. Nistal, M., Abaurrea, M. A. & Paniagua, R. Morphological and histometric study on the human Sertoli cell from birth to the onset of puberty. J. Anat. 14, 351-363 (1982).
29. Weber, J. E., Russell, L. D., Wong, v. & Peterson, R. N. Three dimensional reconstruction of a rat stage v Sertoli cell: ii. Morphometry of Sertoli-Sertoli and Sertoli-germ cell relationships. Am. J. Anat. 167, 163-179 (1983).
30. Sinha Hikim, A. P. & Swerdloff, R. S. Hormonal and genetic control of germ cell apoptosis in the testis. Rev. Reprod. 4, 38-47 (1999).
31. Bartke, A. Apoptosis of male germ cells, a generalized or cell type-specific phenomenon? Endocrinology 136, 3-4 (1995).
32. Setchell, B. P. in Molecular Mechanisms in Spermatogenesis (ed. Cheng, C. Y.) 212-233 (Landes Bioscience/Springer Science+Business Media, Austin, TX, 2008).
33. Dym, M. & Cavicchia, J. C. Functional morphology of the testis. Biol. Reprod. 18, 1-15 (1978).
34. Xia, W., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Differential interactions between transforming growth factor-beta3/TbetaR1, TAB1, and CD2AP disrupt blood-testis barrier and Sertoli-germ cell adhesion. J. Biol. Chem. 281, 16799-16813 (2006).
35. Li, M. W. et al. TNFalpha reversibly disrupts the blood-testis barrier and impairs Sertoli-germ cell adhesion in the seminiferous epithelium of adult rat testes. J. Endocrinol. 190, 313-329 (2006).
36. Lui, W. Y., Wong, C. H., Mruk, D. D. & Cheng, C. Y. TGF-beta3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: an in vivo study. Endocrinology 144, 1139-1142 (2003).
37. Wong, C. H., Mruk, D. D., Lui, W. Y. & Cheng, C. Y. Regulation of blood-testis barrier dynamics: an in vivo study. J. Cell Sci. 117, 783-798 (2004).
38. Meng, J., Holdcraft, R. W., Shima, J. E., Griswold, M. D. & Braun, R. E. Androgens regulate the permeability of the blood-testis barrier. Proc. Natl Acad. Sci. USA 102, 16696-116670 (2005).
39. Wang, R. S. et al. Androgen receptor in Sertoli cell is essential for germ cell nursery and junction complex formation in mouse testes. Endocrinology 147, 5624-5633 (2006).
40. Yan, H. H., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells. FASEB J. 22, 1945-1959 (2008).
41. Li, M. W., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Connexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics. Proc. Natl Acad. Sci. USA 106, 10213-10218 (2009).
42. Lie, P. P., Cheng, C. Y. & Mruk, D. D. Crosstalk between desmoglein-2/desmocollin-2/Src kinase and coxsackie and adenovirus receptor/ ZO-1 protein complexes, regulates blood-testis barrier dynamics. Int. J. Biochem. Cell Biol. 42, 975-986 (2010).
43. Russell, L. Observations on rat Sertoli ectoplasmic ('junctional') specializations in their association with germ cells of the rat testis. Tissue Cell 9, 475-498 (1977).
44. vogl, A., vaid, K. & Guttman, J. in Molecular Mechanisms in Spermatogenesis (ed. Cheng, C. Y.) 186-211 (Landes Bioscience/ Springer Science+Business Media, Austin, TX, 2008).
45. Mruk, D. D., Silvestrini, B. & Cheng, C. Y. Anchoring junctions as drug targets: role in contraceptive development. Pharmacol. Rev. 60, 146-180 (2008).
46. Wong, C. H. & Cheng, C. Y. The blood-testis barrier: its biology, regulation and physiological role in spermatogenesis. Curr. Top. Dev. Biol. 71, 263-296 (2005).
47. Setchell, B. P. & Waites, G. M. B. in The Handbook of Physiology, Section 7, vol.5 (eds Hamilton, D. W. & Greep, R. O.) 143-172 (American Physiological Society, Washington, D. C., 1975).
48. Fawcett, D. W., Leak, L. v. & Heidger, P. M. Jr Electron microscopic observations on the structural components of the blood-testis barrier. J. Reprod. Fertil. Suppl. 10, 105-122 (1970).
49. Dym, M. & Fawcett, D. W. The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium. Biol. Reprod. 3, 308-326 (1970).
50. Dym, M. The fine structure of the monkey (Macaca) Sertoli cell and its role in maintaining the blood-testis barrier. Anat. Rec. 175, 639-656 (1973).
51. Fawcett, D. W. intercellular bridges. Exp. Cell Res. 8, 174-187 (1961).
52. Mruk, D. D. & Cheng, C. Y. Delivering nonhormonal contraceptives to men: advances and obstacles. Trends Biotechnol. 26, 90-99 (2008).
53. Yan, H. H. & Cheng, C. Y. Blood-testis barrier dynamics are regulated by an engagement/ disengagement mechanism between tight and adherens junctions via peripheral adaptors. Proc. Natl Acad. Sci. USA 102, 11722-11727 (2005).
54. Yan, H. H., Mruk, D. D., Lee, W. M. & Cheng, C. Y. in Molecular Mechanisms in Spermatogenesis (ed. Cheng, C. Y.) 234-254 (Landes Bioscience and Springer Science+Business Media, Austin, TX, 2008).
55. Lie, P. P., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Cytoskeletal dynamics and spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1581-1592 (2010).
56. Yan, H. H., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Ectoplasmic specialization: a friend or a foe of spermatogenesis? Bioessays 29, 36-48 (2007).
57. Wong, E. W., Mruk, D. D. & Cheng, C. Y. Biology and regulation of ectoplasmic specialization, an atypical adherens junction type, in the testis. Biochim. Biophys. Acta 1778, 692-708 (2008).
58. Yan, H. H. & Cheng, C. Y. Laminin alpha3 forms a complex with beta3 and gamma3 chains that serves as the ligand for alpha6beta1-integrin at the apical ectoplasmic specialization in adult rat testes. J. Biol. Chem. 281, 17286-17303 (2006).
59. Siu, M. K. & Cheng, C. Y. interactions of proteases, protease inhibitors, and the beta1 integrin/laminin gamma3 protein complex in the regulation of ectoplasmic specialization dynamics in the rat testis. Biol. Reprod. 70, 945-964 (2004).
60. Lee, N. P., Mruk, D. D., Lee, W. M. & Cheng, C. Y. is the cadherin/catenin complex a functional unit of cell-cell-actin-based adherens junctions (AJ) in the rat testis? Biol. Reprod. 68, 489-508 (2003).
61. Johnson, K. & Boekelheide, K. Dynamic testicular adhesion junctions are immunologically unique. ii. Localization of classic cadherins in rat testis. Biol. Reprod. 66, 992-1000 (2002). (Pubitemid 34263119)
62. Wolski, K. M., Perrault, C., Tran-Son-Tay, R. & Cameron, D. F. Strength measurement of the Sertoli-spermatid junctional complex. J. Androl. 26, 354-359 (2005).
63. Cheng, C. Y. et al. AF-2364 [1-(2,4- dichlorobenzyl)-1H-indazole-3- carbohydrazide] is a potential male contraceptive: a review of recent data. Contraception 72, 251-261 (2005).
64. Wolski, K. M., Mruk, D. D. & Cameron, D. F. The Sertoli-spermatid junctional complex adhesion strength is affected in vitro by adjudin. J. Androl. 27, 790-794 (2006).
65. Chen, Y. M., Lee, N. P., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Fer kinase/FerT and adherens junction dynamics in the testis: an in vitro and in vivo study. Biol. Reprod. 69, 656-672 (2003).
66. Yan, H. H., Mruk, D. D., Wong, E. W., Lee, W. M. & Cheng, C. Y. An autocrine axis in the testis that coordinates spermiation and blood-testis barrier restructuring during spermatogenesis. Proc. Natl Acad. Sci. USA 105, 8950-8955 (2008).
67. Carraway, C. A. & Carraway, K. L. Sequestration segregation of receptor kinases in epithelial cells: implications for ErbB2 oncogenesis. Sci. STKE 2007, re3 (2007).
68. Durbeej, M. Laminins. Cell Tissue Res. 339, 259-268 (2010).
69. Siu, M. K. & Cheng, C. Y. Dynamic cross-talk between cells and the extracellular matrix in the testis. Bioessays 26, 978-992 (2004).
70. Tzu, J. & Marinkovich, M. P. Bridging structure with function: Structure, regulatory, and developmental role of laminins. Int. J. Biochem. Cell Biol. 40, 199-214 (2008).
71. Yan, H. H., Mruk, D. D. & Cheng, C. Y. Junction restructuring and spermatogenesis: the biology, regulation, and implication in male contraceptive development. Curr. Top. Dev. Biol. 80, 57-92 (2008).
72. Adair-Kirk, T. L. & Senior, R. M. Fragments of extracellular matrix as mediators of inflammation. Int. J. Biochem. Cell Biol. 40, 1101-1110 (2008).
73. Koch, M. et al. Characterization and expression of the laminin gamma3 chain: a novel, nonbasement membrane-associated, laminin chain. J. Cell Biol. 145, 605-618 (1999).
74. Obholz, K. L., Akopyan, A., Waymire, K. G. & MacGregor, G. R. FNDC3A is required for adhesion between spermatids and Sertoli cells. Dev. Biol. 298, 498-513 (2006).
75. Bulgakova, N. A. & Knust, E. The Crumbs complex: from epithelial-cell polarity to retinal degeneration. J. Cell Sci. 122, 2587-2596 (2009).
76. Assemat, E., Bazellieres, E., Pallesi-Pocachard, E., Le Bivic, A. & Massey-Harroche, D. Polarity complex proteins. Biochim. Biophys. Acta 1778, 614-630 (2008).
77. Shin, K., Fogg, v. C. & Margolis, B. Tight junctions and cell polarity. Annu. Rev. Cell Dev. Biol. 22, 207-235 (2006).
78. Wu, J. & Mlodzik, M. A quest for the mechanism regulating global planar cell polarity of tissues. Trends Cell Biol. 19, 295-305 (2009).
79. iden, S. & Collard, J. G. Crosstalk between small GTPases and polarity proteins in cell polarization. Nat. Rev. Mol. Cell Biol. 9, 846-859 (2008).
80. Wong, E. W., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood-testis barrier restructuring during spermatogenesis. Proc. Natl Acad. Sci. USA 105, 9657-9662 (2008).
81. Wong, E. W. & Cheng, C. Y. Polarity proteins and cell-cell interactions in the testis. Int. Rev. Cell. Mol. Biol. 278, 309-353 (2009).
82. Lee, M. & vasioukhin, v. Cell polarity and cancercell and tissue polarity as a non-canonical tumor suppressor. J. Cell Sci. 121, 1141-1150 (2008).
83. Kemphues, K. J., Priess, J. R., Morton, D. G. & Cheng, N. S. identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52, 311-320 (1988).
84. Wong, E. W., Sun, S., Li, M. W., Lee, W. M. & Cheng, C. Y. 14-3-3 protein regulates cell adhesion in the seminiferous epithelium of rat testes. Endocrinology 150, 4713-4723 (2009).
85. Russell, L. D. Further observations on tubulobulbar complexes formed by late spermatids and Sertoli cells in the rat testis. Anat. Rec. 194, 213-232 (1979).
86. Russell, L. D. Spermatid-Sertoli tubulobulbar complexes as devices for elimination of cytoplasm from the head region in late spermatids of the rat. Anat. Rec. 194, 233-246 (1979).
87. Russell, L. D. Observations on the interrelationships of Sertoli cells at the level of the blood-testis barrier: evidence for formation and resorption of Sertoli-Sertoli tubulobulbar complexes during the spermatogenic cycle of the rat. Am. J. Anat. 155, 259-279 (1979).
88. Young, J. S., Guttman, J. A., vaid, K. S. & vogl, A. W. Tubulobulbar complexes are intercellular podosome-like structures that internalize intact intercellular junctions during epithelial remodeling events in the rat testis. Biol. Reprod. 80, 162-174 (2009).
89. Young, J. S., Guttman, J. A., vaid, K. S., Shahinian, H. & vogl, A. W. Cortactin (CTTN), N-WASP (WASL), and clathrin (CLTC) are present at podosome-like tubulobulbar complexes in the rat testis. Biol. Reprod. 80, 153-161 (2009).
90. Fletcher, S. J. & Rappoport, J. Z. The role of vesicle trafficking in epithelial cell motility. Biochem. Soc. Trans. 37, 1072-1076 (2009).
91. Derivery, E. & Gautreau, A. Generation of branched actin networks: assembly and regulation of the N-WASP and WAvE molecular machines. Bioessays 32, 119-131 (2010).
92. Walsh, S. v., Hopkins, A. M. & Nusrat, A. Modulation of tight junction structure and function by cytokines. Adv. Drug Deliv. Rev. 41, 303-313 (2000). (Pubitemid 30347380)
93. Xia, W., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Cytokines and junction restructuring during spermatogenesis-a lesson to learn from the testis. Cytokine Growth Factor Rev. 16, 469-493 (2005).
94. Turner, J. R. intestinal mucosal barrier function in health and disease. Nat. Rev. Immunol. 9, 799-809 (2009).
95. Li, M. W., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Cytokines and junction restructuring events during spermatogenesis in the testis: An emerging concept of regulation. Cytokine Growth Factor Rev. 20, 329-338 (2009).
96. Koch, S. & Nusrat, A. Dynamic regulation of epithelial cell fate and barrier function by intercellular junctions. Ann. NY Acad. Sci. 1165, 220-227 (2009).
97. Kirschner, N. et al. Alteration of tight junction proteins is an early event in psoriasis: Putative involvement of proinflammatory cytokines. Am. J. Pathol. 175, 1095-1106 (2009).
98. Clayburgh, D. R. et al. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J. Clin. Invest. 115, 2702-2715 (2005).
99. Lui, W. Y., Lee, W. M. & Cheng, C. Y. Transforming growth factor-b3 perturbs the inter-Sertoli tight junction permeability barrier in vitro possibly mediated via its effects on occludin, zonula occludens-1, and claudin-11. Endocrinology 142, 1865-1877 (2001).
100. Lui, W. Y., Lee, W. M. & Cheng, C. Y. Transforming growth factor-beta3 regulates the dynamics of Sertoli cell tight junctions via the p38 mitogenactivated protein kinase pathway. Biol. Reprod. 68, 1597-1612 (2003).
101. Siu, M. K., Lee, W. M. & Cheng, C. Y. The interplay of collagen iv, tumor necrosis factor-alpha, gelatinase B (matrix metalloprotease-9), and tissue inhibitor of metalloproteases-1 in the basal lamina regulates Sertoli cell-tight junction dynamics in the rat testis. Endocrinology 144, 371-387 (2003).
102. Xia, W. & Cheng, C. Y. TGF-beta3 regulates anchoring junction dynamics in the seminiferous epithelium of the rat testis via the Ras/ERK signaling pathway: An in vivo study. Dev. Biol. 280, 321-343 (2005).
103. Wong, C. H., Mruk, D. D., Siu, M. K. & Cheng, C. Y. Blood-testis barrier dynamics are regulated by alpha2-macroglobulin via the c-Jun N-terminal protein kinase pathway. Endocrinology 146, 1893-1908 (2005).
104. Pentikainen, v. et al. TNF-alpha down-regulated the Fas ligand and inhibits germ cell apoptosis in the human testis. J. Clin. Endocrinol. Metab. 86, 4480-4488 (2001).
105. Suominen, J. S., Wang, Y., Kaipia, A. & Toppari, J. Tumor necrosis factor-alpha (TNF-alpha) promotes cell survival during spermatogenesis, and this effect can be blocked by infliximab, a TNF-alpha antagonist. Eur. J. Endocrinol. 151, 629-640 (2004).
106. Wong, v. & Russell, L. D. Three-dimensional reconstruction of a rat stage v Sertoli cell: i. Methods, basic configuration, and dimensions. Am. J. Anat. 167, 143-161 (1983). (Pubitemid 13069013)
107. Lui, W. Y., Lee, W. M. & Cheng, C. Y. TGF-betas: their role in testicular function and Sertoli cell tight junction dynamics. Int. J. Androl. 26, 147-160 (2003).
108. Loveland, K. L., Dias, v., Meachem, S. & Rajpert-De Meyts, E. The transforming growth factor-beta superfamily in early spermatogenesis: potential relevance to testicular dysgenesis. Int. J. Androl. 30, 377-384 (2007).
109. O'Bryan, M. K. & Hedger, M. P. in Molecular Mechanisms in Spermatogenesis (ed. Cheng, C. Y.) 92-114 (Landes Bioscience and Springer Science+Business Media, Austin, TX, 2008).
110. Lui, W. Y. & Cheng, C. Y. Regulation of cell junction dynamics by cytokines in the testis-a molecular and biochemical perspective. Cytokine Growth Factor Rev. 18, 299-311 (2007).
111. Li, M. W., Mruk, D. D. & Cheng, C. Y. "Unlocking" the blood-testis barrier and the ectoplasmic specialization by cytokines during spermatogenesis: Emerging targets for male contraception. Immun. Endocr. Metab. Agents Med. Chem. 8, 20-27 (2008).
112. Li, M. W., Mruk, D. D. & Cheng, C. Y. Mitogenactivated protein kinases in male reproductive function. Trends Mol. Med. 15, 159-168 (2009).
113. Xia, W., Wong, E. W., Mruk, D. D. & Cheng, C. Y. TGF-beta3 and TNFalpha perturb blood-testis barrier (BTB) dynamics by accelerating the clathrin-mediated endocytosis of integral membrane proteins: a new concept of BTB regulation during spermatogenesis. Dev. Biol. 327, 48-61 (2009).
114. Syed, v. et al. Residual bodies activate Sertoli cell interleukin-1alpha (iL-1alpha) release, which triggers iL-6 production by an autocrine mechanism, through the lipoxygenase pathway. Endocrinology 136, 3070-3078 (1995).
115. Sarkar, O., Mathur, P. P., Cheng, C. Y. & Mruk, D. D. interleukin 1 alpha (iL1A) is a novel regulator of the blood-testis barrier in the rat. Biol. Reprod. 78, 445-454 (2008).
116. Siu, E. R., Wong, E. W., Mruk, D. D., Porto, C. S. & Cheng, C. Y. Focal adhesion kinase is a blood- testis barrier regulator. Proc. Natl Acad. Sci. USA 106, 9298-9303 (2009).
117. Chung, N. P. & Cheng, C. Y. is cadmium chlorideinduced 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 142, 1878-1888 (2001).
118. 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. 112, 51-57 (1992).
119. Turner, T. T. et al. On the androgen microenvironment of maturing spermatozoa. Endocrinology 115, 1925-1932 (1984).
120. Jarow, J. P. & Zirkin, B. R. The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann. NY Acad. Sci. 1061, 208-220 (2005).
121. Beardsley, A., Robertson, D. M. & O'Donnell, L. A complex containing alpha6beta1-integrin and phosphorylated focal adhesion kinase between Sertoli cells and elongated spermatids during spermatid release from the seminiferous epithelium. J. Endocrinol. 190, 759-770 (2006).
122. Zhang, J. et al. Regulation of Sertoli-germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-beta- catenin protein complex which are possibly mediated by c-Src and myotubularinrelated protein 2: an in vivo study using an androgen suppression model. Endocrinology 146, 1268-1284 (2005).
123. Wong, C. H. et al. Regulation of ectoplasmic specialization dynamics in the seminiferous epithelium by focal adhesion-associated proteins in testosterone-suppressed rat testes. Endocrinology 146, 1192-1204 (2005).
124. Xia, W., Wong, C. H., Lee, N. P., Lee, W. M. & Cheng, C. Y. 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. 205, 141-157 (2005).
125. Delfino, F. J., Boustead, J. N., Fix, C. & Walker, W. H. NF-kappaB and TNF-alpha stimulate androgen receptor expression in Sertoli cells. Mol. Cell. Endocrinol. 201, 1-12 (2003).
126. Yao, P. L., Lin, Y. C. & Richburg, J. H. Mono-(2- ethylhexyl) phthalate-induced disruption of junctional complexes in the seminiferous epithelium of the rodent testis is mediated by MMP2. Biol. Reprod. 82, 516-527 (2010).
127. Yao, P. L., Lin, Y. C. & Richburg, J. H. TNF alphamediated disruption of spermatogenesis in response to Sertoli cell injury in rodents is partially regulated by MMP2. Biol. Reprod. 80, 581-589 (2009).
128. Page-McCaw, A., Ewald, A. J. & Werb, Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell Biol. 8, 221-233 (2007).
129. Heino, J. & Kapyla, J. Cellular receptors of extracellular matrix molecules. Curr. Pharm. Des. 15, 1309-1317 (2009).
130. Ortega, N. & Werb, Z. New functional roles for non-collagenous domains of basement membrane collagens. J. Cell Sci. 115, 4201-4214 (2002).
131. Heino, J. The collagen family members as cell adhesion proteins. Bioessays 29, 1001-1010 (2007).
132. Siu, E. R. et al. An occludin-focal adhesion kinase protein complex at the blood-testis barrier: a study using the cadmium model. Endocrinology 150, 3336-3344 (2009).
133. Siu, M. K., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Adhering junction dynamics in the testis are regulated by an interplay of beta1-integrin and focal adhesion complex-associated proteins. Endocrinology 144, 2141-2163 (2003).
134. Boutros, T., Chevet, E. & Metrakos, P. Mitogenactivated protein (MAP) kinase/MAP kinase phosphatase regulation: Roles in cell growth, death, and cancer. Pharmacol. Rev. 60, 261-310 (2008).
135. Lee, N. P. & Cheng, C. Y. Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis. J. Cell. Physiol. 202, 344-360 (2005).
136. Setchell, B. P. & Waites, G. M. Changes in the permeability of the testicular capillaries and of the "blood-testis barrier" after injection of cadmium chloride in the rat. J. Endocrinol. 47, 81-86 (1970).
137. Hew, K. W., Heath, G. L., Jiwa, A. H. & Welsh, M. J. Cadmium in vivo causes disruption of tight junction-associated microfilaments in rat Sertoli cells. Biol. Reprod. 49, 840-849 (1993).
138. Sakakibara, A., Furuse, M., Saitou, M., Ando- Akatsuka, Y. & Tsukita, S. Possible involvement of phosphorylation of occludin in tight junction formation. J. Cell Biol. 137, 1393-1401 (1997). (Pubitemid 27265950)
139. Tsukamoto, T. & Nigam, S. K. Role of tyrosine phosphorylation in the reassembly of occludin and other tight junction proteins. Am. J. Physiol. Renal Physiol. 276, F737-F750 (1999).
140. Lui, W. Y., Lee, W. M. & Cheng, C. Y. Sertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LiMK signaling pathway. Biol. Reprod. 68, 2189-2206 (2003).
141. Guttman, J. A., Kimel, G. H. & vogl, A. W. Dynein and plus-end microtubule-dependent motors are associated with specialized Sertoli cell junction plaques (ectoplasmic specializations). J. Cell Sci. 113, 2167-2176 (2000).
142. Mulholland, D. J., Dedhar, S. & vogl, A. W. Rat seminiferous epithelium contains a unique junction (ectoplasmic specialization) with signaling properties both of cell/cell and cell/ matrix junctions. Biol. Reprod. 64, 396-407 (2001).
143. Lie, P. P., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium. FASEB J. 23, 2555-2567 (2009).
144. Lie, P. P. et al. Dynamin ii interacts with the cadherin- and occludin-based protein complexes at the blood-testis barrier in adult rat testes. J. Endocrinol. 191, 571-586 (2006).
145. Lee, N. P., Mruk, D. D., Conway, A. M. & Cheng, C. Y. Zyxin, axin, and Wiskott-Aldrich syndrome protein are adaptors that link the cadherin/catenin protein complex to the cytoskeleton at adherens junctions in the seminiferous epithelium of the rat testis. J. Androl. 25, 200-215 (2004).
146. Cheng, C. Y. & Mruk, D. D. Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol. Rev. 82, 825-874 (2002).
147. vaid, K. S., Guttman, J. A., Singaraja, R. R. & vogl, A. W. A kinesin is present at unique Sertoli/spermatid adherens junctions in rat and mouse testes. Biol. Reprod. 77, 1037-1048 (2007).
148. Mruk, D. D., Lau, A. S., Sarkar, O. & Xia, W. Rab4A GTPase-catenin interactions are involved in cell junction dynamics in the testis. J. Androl. 28, 742-754 (2007).
149. Mruk, D. D. & Lau, A. S. RAB13 participates in ectoplasmic specialization dynamics in the rat testis. Biol. Reprod. 80, 590-601 (2009).
150. Le Magueresse-Battistoni, B. Serine proteases and serine protease inhibitors in testicular physiology: the plasminogen activation system. Reproduction 134, 721-729 (2007).
151. Kaitu'u-Lino, T. J., Sluka, P., Foo, C. F. & Stanton, P. G. Claudin-11 expression and localisation is regulated by androgens in rat Sertoli cells in vitro. Reproduction 133, 1169-1179 (2007).
152. Walker, W. H. Molecular mechanisms of testosterone action in spermatogenesis. Steroids 74, 602-607 (2009).
153. Barker, C. F. & Billingham, R. E. immunologically privileged sites. Adv. Immunol. 25, 1-54 (1977).