Proteases and Their Cognate Inhibitors of the Serine and Metalloprotease Subclasses, in Testicular Physiology

  • Brigitte Le Magueresse-BattistoniEmail author
Part of the Advances in Experimental Medicine and Biology book series (volume 636)


The testis is a highly dynamic organ not only in the fetal stage but also during postnatal development and in adult life. It is composed of two major compartments: the interstitium with the steroidogenic Leydig cells, and the seminiferous tubules. The seminiferous tubules are surrounded by peritubular cells. Tubules are composed of Sertoli cells and germ cells at different developmental stages. Sertoli cells play key roles in spermatogenesis. They are target cells for follicle stimulating hormone (FSH) and testosterone, responsible for the initiation and maintenance of spermatogenesis. They form the tubules and provide structural and nutritional support for the developing germ cells1, 2, 3, 4.


Germ Cell Plasminogen Activator Follicle Stimulate Hormone Sertoli Cell Leydig 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.
    Russell LD. Sertoli-germ cell interrelations: A review. Gamete Res 1980; 3:79–202.CrossRefGoogle Scholar
  2. 2.
    Jegou B, Sharpe RM. Paracrine mechanisms in testicular control. In: de Kretser DM, ed. Molecular Biology of the Male Reproductive System. San Diego: Academic Press, 1993:271–310.Google Scholar
  3. 3.
    de Kretser DM, Loveland KL, Meinhardt A et al. Spermatogenesis. Hum Reprod 1998; 13(Suppl. 1):1–8.PubMedGoogle Scholar
  4. 4.
    Griswold MD. The central role of Sertoli cells seminiferous epithelium. Semin Cell Dev Biol 1998; 9:411–416.PubMedCrossRefGoogle Scholar
  5. 5.
    McElreavey K, Fellous M. Sex determination and the Y chromosome. Am J Med Genet 1999; 89(4):176–185.PubMedCrossRefGoogle Scholar
  6. 6.
    Swain A, Lovell-Badge R. Mammalian sex determination: A molecular drama. Genes Dev 1999; 13:755–767.PubMedCrossRefGoogle Scholar
  7. 7.
    Josso N, Racine C, Di Clemente N et al. The role of anti-Müllerian hormone in gonadal development. Mol Cell Endocrinol 1998; 145:3–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Yao HH, Tilmann C, Zhao GO et al. The battle of the sexes: Opposing pathways in sex determination. In: Chadwick D, Goode J, eds. Symposium on the Genetics and Biology of Sex Determination. London: Novartis Foundation, 2002:187–198.CrossRefGoogle Scholar
  9. 9.
    Brennan J, Capel B. One tissue, two fates: Molecular genetic events that underlie testis versus ovary development. Nat Rev Genet 2004; 5(7):509–521.PubMedCrossRefGoogle Scholar
  10. 10.
    Koopman P. Sex determination: A tale of two Sox genes. Trends Genet 2005; 21(7):367–370.PubMedCrossRefGoogle Scholar
  11. 11.
    Töhönen V, Osterlund C, Nordqvist K. Testatin: A cystatin-related gene expressed during early testis development. Proc Natl Acad Sci USA 1998; 95(24):14208–14213.PubMedCrossRefGoogle Scholar
  12. 12.
    Grimmond S, Van Hateren N, Siggers P et al. Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development. Hum Mol Genet 2000; 9(10):1553–1560.PubMedCrossRefGoogle Scholar
  13. 13.
    Guyot R, Magre S, Leduque P et al. Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) during mouse gonad development. Dev Dyn 2003; 227(3):357–366.PubMedCrossRefGoogle Scholar
  14. 14.
    Fritz IB, Tung PS, Ailenberg M. Proteases and antiproteases in the seminiferous tubules. In: Russell LD, Griswold MD, eds. The Sertoli Cell. Clearwater: Cache River Press, 1993:217–235.Google Scholar
  15. 15.
    Charron M, Wright WW. Proteases and protease inhibitors. In: Skinner MK, Griswold MD, eds. Sertoli Cell Biology. London: Elsevier Academic Press, 2005:121–152.CrossRefGoogle Scholar
  16. 16.
    Wong CH, Cheng CY. The blood-testis barrier: Its biology, regulation, and physiological role in spermatogenesis. Curr Top Dev Biol 2005; 71:263–296.PubMedCrossRefGoogle Scholar
  17. 17.
    Longin J, Guillaumot P, Chauvin MA et al. MT1-MMP in rat testicular development and the control of Sertoli cell proMMP-2 activation. J Cell Science 2001; 114(Pt 11):2125–2134.PubMedGoogle Scholar
  18. 18.
    Vu TH, Werb Z. Matrix metalloproteinases: Effectors of development and normal physiology. Genes Dev 2000; 14(17):2123–2133.PubMedCrossRefGoogle Scholar
  19. 19.
    Puente XS, Sanchez LM, Overall CM et al. Human and mouse proteases: A comparative genomic approach. Nat Rev Genet 2003; 4(7):544–558.PubMedCrossRefGoogle Scholar
  20. 20.
    Puente XS, Lopez-Otin C. A genomic analysis of rat proteases and protease inhibitors. Genome Res 2004; 4(4):609–622.CrossRefGoogle Scholar
  21. 21.
    Curry TEJ, Osteen KG. The matrix metalloproteinase system: Changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev 2003; 24(4):428–465.PubMedCrossRefGoogle Scholar
  22. 22.
    Gabison EE, Hoang-Xuan T, Mauviel A et al. EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie 2005; 87(3–4):361–368.PubMedCrossRefGoogle Scholar
  23. 23.
    Primakoff P, Myles DG: The ADAM gene family: Surface proteins with adhesion and protease activity. Trends Genet 2000; 6(2):83–87.CrossRefGoogle Scholar
  24. 24.
    Apte SS. A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motifs: The ADAMTS family. Int J Biochem Cell Biol 2004; 36(6):981–985.PubMedCrossRefGoogle Scholar
  25. 25.
    Porter S, Clark IM, Kevorkian L et al. The ADAMTS metalloproteinases. Biochem J 2005; 386(Pt 1):15–27.PubMedGoogle Scholar
  26. 26.
    Edwards DR, Waterhouse P, Holman ML et al. A growth-responsive gene (16C8) in normal mouse fibroblasts homologous to a human collagenase inhibitor with erythroid-potentiating activity: Evidence for inducible and constitutive transcripts. Nucleic Acids Res 1986; 14(22):8863–8878.PubMedCrossRefGoogle Scholar
  27. 27.
    Woessner JFJ. MMPs and TIMPs—An historic perspective Mol Biotechnol 2002; 22(1):33–49.PubMedCrossRefGoogle Scholar
  28. 28.
    Lambert E, Dasse E, Haye B et al. TIMPs as multifacial proteins. Crit Rev Oncol Hematol 2004; 49(3):187–198.PubMedCrossRefGoogle Scholar
  29. 29.
    Stetler-Stevenson WG, Seo DW. TIMP-2: An endogenous inhibitor of angiogenesis. Trends Mol Med 2005; 11(3):97–103.PubMedCrossRefGoogle Scholar
  30. 30.
    Mannello F, Gazzanelli G. Tissue inhibitors of metalloproteinases and programmed cell death: Conundrums, controversies and potential implications. Apoptosis 2001; 6(6):479–482.PubMedCrossRefGoogle Scholar
  31. 31.
    Weber BH, Vogt G, Pruett RC et al. Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP-3) in patients with Sorsby’s fundus dystrophy. Nat Genet 1994; 8(4):352–356.PubMedCrossRefGoogle Scholar
  32. 32.
    Fata JE, Leo KJ, Voura EB et al. Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest 2001; 108(6):831–841.PubMedGoogle Scholar
  33. 33.
    Carmeliet P, Collen D. Development and disease in proteinase-deficient mice: Role of the plasminogen, matrix metalloproteinase and coagulation system. Thromb Res 1998; 91(6):255–285.PubMedCrossRefGoogle Scholar
  34. 34.
    Dano K, Behrendt N, Hoyer-Hansen G et al. Plasminogen activation and cancer. Thromb Haemost 2005; 93(4):676–681.PubMedGoogle Scholar
  35. 35.
    Leonardsson G, Peng XR, Liu K et al. Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: Functional redundancy among physiological plasminogen activators. Proc Natl Acad Sci USA 1995; 92(26):12446–12450.PubMedCrossRefGoogle Scholar
  36. 36.
    Ny T, Wahlberg P, Brandstrom IJ. Matrix remodeling in the ovary: Regulation and functional role of the plasminogen activator and matrix metalloproteinase systems. Mol Cell Endocrinol 2002; 187(1–2):29–38.PubMedCrossRefGoogle Scholar
  37. 37.
    Hajjar KA. Cellular receptors in the regulation of plasmin generation. Thromb Haemost 1995; 74(1):294–301.PubMedGoogle Scholar
  38. 38.
    Kim J, Hajjar KA. Annexin II: A plasminogen-plasminogen activator coreceptor. Front Biosci 2002; 7:d341–d348.PubMedCrossRefGoogle Scholar
  39. 39.
    Solberg H, Lober D, Eriksen J et al. Identification and characterization of the murine cell surface receptor for the urokinase-type plasminogen activator. Eur J Biochem 1992; 205(2):451–458.PubMedCrossRefGoogle Scholar
  40. 40.
    Blasi F, Carmeliet P. uPAR: A versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3(12):932–943.PubMedCrossRefGoogle Scholar
  41. 41.
    Alfano D, Franco P, Vocca I et al. The urokinase plasminogen activator and its receptor: Role in cell growth and apoptosis. Thromb Haemost 2005; 93(2):205–211.PubMedGoogle Scholar
  42. 42.
    Hooper JD, Clements JA, Quigley JP et al. Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J Biol Chem 2001; 276(2):857–860.PubMedCrossRefGoogle Scholar
  43. 43.
    Diamandis EP, Yousef GM. Human tissue kallikreins: A family of new cancer biomarkers. Clin Chem 2002; 48(8):1198–1205.PubMedGoogle Scholar
  44. 44.
    Diamandis EP, Yousef GM, Olsson AY. An update on human and mouse glandular kallikreins. Clin Biochem 2004; 37(4):258–260.PubMedCrossRefGoogle Scholar
  45. 45.
    Potempa J, Korzus E, Travis J. The serpin superfamily of proteinase inhibitors: Structure, function, and regulation. J Biol Chem 1994; 269(23):15957–15960.PubMedGoogle Scholar
  46. 46.
    Silverman GA, Bird PI, Carrell RW et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 2001; 276(36):33293–33296.PubMedCrossRefGoogle Scholar
  47. 47.
    Gettins PG. Serpin structure, mechanism, and function. Chem Rev 2002; 102(12):4751–4804.PubMedCrossRefGoogle Scholar
  48. 48.
    Pike RN, Buckle AM, Le Bonniec BF et al. Control of the coagulation system by serpins. Getting by with a little help from glycosaminoglycans. FEBS J 2005; 272(19):4842–4851.PubMedCrossRefGoogle Scholar
  49. 49.
    Jerabek I, Zechmeister-Machhart M, Binder BR et al. Binding of retinoic acid by the inhibitory serpin protein C inhibitor. Eur J Biochem 2001; 268(22):5989–5996.PubMedCrossRefGoogle Scholar
  50. 50.
    Nuttall RK, Sampieri CL, Pennington CJ et al. Expression analysis of the entire MMP and TIMP gene families during mouse tissue development. FEBS Lett 2004; 563(1–3):129–134.PubMedCrossRefGoogle Scholar
  51. 51.
    Ulisse S, Farina AR, Piersanti D et al. Follicle-stimulating hormone increases the expression of tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 and induces TIMP-1 AP-1 site binding complex(es) in prepubertal rat Sertoli cells. Endocrinology 1994; 135(6):2479–2487.PubMedCrossRefGoogle Scholar
  52. 52.
    Boujrad N, Ogwuegbu SO, Garnier M et al. Identification of a stimulator of steroid hormone synthesis isolated from testis. Science 1995; 268(5217):1609–1612.PubMedCrossRefGoogle Scholar
  53. 53.
    Hoeben E, Van Haelst I, Swinnen JV et al. Gelatinase A secretion and its control in peritubular and Sertoli cell cultures: Effects of hormones second messengers and inducers of cytokine production. Mol Cell Endocrinol 1996; 118(1–2):37–46.PubMedCrossRefGoogle Scholar
  54. 54.
    Gronning LM, Wang JE, Ree AH et al. Regulation of tissue inhibitor of metalloproteinases-1 in rat Sertoli cells: Induction by germ cell residual bodies, interleukin-1 alpha and second messengers. Biol Reprod 2000; 62(4):1040–1046.PubMedCrossRefGoogle Scholar
  55. 55.
    Longin J, Le Magueresse-Battistoni B. Evidence that MMP-2 and TIMP-2 are at play in the FSH-induced changes in Sertoli cells. Mol Cell Endocrinol 2002; 189(1–2):25–35.PubMedCrossRefGoogle Scholar
  56. 56.
    Nishino K, Yamanouchi K, Naito K et al. Matrix metalloproteinases regulate mesonephric cell migration in developing XY gonads which correlates with the inhibition of tissue inhibitor of metalloproteinase-3 by Sry. Dev Growth Differ 2002; 44(1):35–43.PubMedCrossRefGoogle Scholar
  57. 57.
    Mruk DD, Siu MK, Conway AM et al. Role of tissue inhibitor of metalloproteases-1 in junction dynamics in the testis. J Androl 2003; 24(4):510–523.PubMedGoogle Scholar
  58. 58.
    Siu MK, Lee WM, Cheng CY. The interplay of collagen IV, tumor necrosis factor-α, 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 2003; 144(1):371–387.PubMedCrossRefGoogle Scholar
  59. 59.
    Siu MK, Cheng CY. Interactions of proteases, protease inhibitors, and the betal integrin/laminin gamma3 protein complex in the regulation of ectoplasmic specialization dynamics in the rat testis. Biol Reprod 2004; 70(4):945–964.PubMedCrossRefGoogle Scholar
  60. 60.
    Siu MK, Cheng CY: Dynamic cross-talk between cells and the extracellular matrix in the testis. Bioessays 2004; 26(9):978–992.PubMedCrossRefGoogle Scholar
  61. 61.
    El Ramy R, Vérot A, Mazaud S et al. Fibroblast growth factor (FGF), 2 and FGF9 mediate mesenchymal-epithelial interactions of peritubular and Sertoli cells in the rat testis. J Endocrinol 2005; 187(1):135–147.PubMedCrossRefGoogle Scholar
  62. 62.
    Bernal F, Hartung HP, Kieseier BC. Tissue mRNA expression in rat of newly described matrix metalloproteinases. Biol Res 2005; 38(2–3):267–271.PubMedGoogle Scholar
  63. 63.
    Cossins J, Dudgeon TJ, Catlin G et al. Identification of MMP-18, a putative novel human matrix metalloproteinase. Biochem Biophys Res Commun 1996; 228(2):494–498.PubMedCrossRefGoogle Scholar
  64. 64.
    Velasco G, Pendas AM, Fueyo A et al. Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J Biol Chem 1999; 274(8):4570–4576.PubMedCrossRefGoogle Scholar
  65. 65.
    Lohi J, Wilson CL, Roby JD et al. Epilysin, a novel human matrix, metalloproteinase (MMP-28) expressed in testis and keratinocytes and in response to injury. J Biol Chem 2001; 276(13):10134–10144.PubMedCrossRefGoogle Scholar
  66. 66.
    Robinson LL, Sznajder NA, Riley SC et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human fetal testis and ovary. Mol Hum Reprod 2001; 7(7):641–648.PubMedCrossRefGoogle Scholar
  67. 67.
    Ailenberg M, Fritz IB. Influences of follicle-stimulating hormone, proteases, and antiproteases on permeability of the barrier generated by Sertoli cells in a two-chambered assembly. Endocrinology 1989;124(3):1399–1407.PubMedCrossRefGoogle Scholar
  68. 68.
    Ailenberg M, Stetler-Stevenson WG, Fritz IB. Secretion of latent type IV procollagenase and active type IV, collagenase by testicular cells in culture. Biochem J 1991; 279(Pt 1):75–80.PubMedGoogle Scholar
  69. 69.
    Liu L, Smith JW. Identification of ADAM 31: A protein expressed in Leydig cells and specialized epithelia. Endocrinology 2000; 141(6):2033–2042.PubMedCrossRefGoogle Scholar
  70. 70.
    Blavier L, DeClerk, YA. Tissue inhibitor of metalloproteinases-2 is expressed in the interstitial matrix in adult mouse organs and during embryonic development. Mol Biol Cell 1997; 8(8):1513–1527.PubMedGoogle Scholar
  71. 71.
    Ge RS, Dong O, Sottas CM et al. Gene expression in rat Leydig cells during development from the progenitor to adult stage: A cluster analysis. Biol Reprod 2005; 72(6):1405–1415.PubMedCrossRefGoogle Scholar
  72. 72.
    Lacroix M, Smith FE, Fritz IB. Changes in levels of plasminogen activator activity in normal and germ-cell-depleted testes during development. Mol Cell Endocrinol 1982; 26(3):259–267.PubMedCrossRefGoogle Scholar
  73. 73.
    Saksela O, Vihko KK. Local synthesis of plasminogen by the seminiferous tubules of the testis. FEBS Lett 1986; 204(2):193–197.PubMedCrossRefGoogle Scholar
  74. 74.
    Vihko KK, Penttila TL, Parvinen M et al. Regulation of urokinase-and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium. Mol Cell Endocrinol 1989; 31(1):52–59.Google Scholar
  75. 75.
    Tolli R, Monaco LDB, Di Bonito P et al. Hormonal regulation of urokinase-and tissue-type plasminogen activator in rat Sertoli cells. Biol Reprod 1995; 53(1):193–200.PubMedCrossRefGoogle Scholar
  76. 76.
    Canipari R, Galdieri M. Retinoid modulation of plasminogen activator production in rat Sertoli cells. Biol Reprod 2000; 63(2):544–550.PubMedCrossRefGoogle Scholar
  77. 77.
    Vihko KK, Kristensen P, Dano K et al. Immunohistochemical localization of urokinase-type plasminogen activator in Sertoli cells and tissue-type plasminogen activator in spermatogenic cells in the rat seminiferous epithelium. Dev Biol 1988; 126(1):150–155.PubMedCrossRefGoogle Scholar
  78. 78.
    O’Shaughnessy PJ, Fleming L, Baker PJ et al. Identification of developmentally regulated genes in the somatic cells of the mouse testis using serial analysis of gene expression. Biol Reprod 2003; 69(3):797–808.PubMedCrossRefGoogle Scholar
  79. 79.
    Odet F, Guyot R, Leduque P et al. Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development. Endocrinology 2004; 145:1481–1489.PubMedCrossRefGoogle Scholar
  80. 80.
    Huarte J, Belin D, Bosco D et al. Plasminogen activator and mouse spermatozoa: Urokinase synthesis in the male genital tract and binding of the enzyme to the sperm cell surface. J Cell Biol 1987; 104(5):1281–1289.PubMedCrossRefGoogle Scholar
  81. 81.
    Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 2005; 93(4):631–640.PubMedGoogle Scholar
  82. 82.
    Sawada H, Sugawara I, Kitami A et al. Vitronectin in the cytoplasm of Leydig cells in the rat testis. Biol Reprod 1996; 54(1):29–35.PubMedCrossRefGoogle Scholar
  83. 83.
    Nuovo GJ, Preissner KT, Bronson RA. PCR-amplified vitronectin mRNA localizes in situ to spermatocytes and round spermatids in the human testis. Hum Reprod 1995; 10(8):2187–2191.PubMedGoogle Scholar
  84. 84.
    Hettle JA, Balekjian E, Tung PS et al. Rat testicular peritubular cells in culture secrete an inhibitor of plasminogen activator activity. Biol Reprod 1988; 38(2):359–371.PubMedCrossRefGoogle Scholar
  85. 85.
    Le Magueresse-Battistoni B, Pernod, G, Sigillo F et al. Plasminogen activator inhibitor-1 is expressed in cultured rat Sertoli cells. Biol Reprod 1998; 59(3):591–598.PubMedCrossRefGoogle Scholar
  86. 86.
    Nargolwalla C, McCabe D, Fritz IB. Modulation of levels of messenger RNA for tissue-type plasminogen activator in rat Sertoli cells, and levels of messenger RNA for plasminogen activator inhibitor in testis peritubular cells. Mol Cell Endocrinol 1990; 70(1):73–80.PubMedCrossRefGoogle Scholar
  87. 87.
    Le Magueresse-Battistoni B, Pernod G, Kolodie L et al. Plasminogen activator inhibitor-1 regulation in cultured rat peritubular cells by basic fibroblast growth factor and transforming growth factor-alpha. Endocrinology 1996; 137(10):4243–4249.PubMedCrossRefGoogle Scholar
  88. 88.
    Le Magueresse-Battistoni B, Pernod G, Kolodie L et al. Tumor necrosis factor-alpha regulates plasminogen activator inhibitor-1 in rat testicular peritubular cells. Endocrinology 1997; 138(3):1097–1105.PubMedCrossRefGoogle Scholar
  89. 89.
    Meachem SJ, Ruwanpura SM, Ziolkowski J et al. Developmentally distinct in vivo effects, of FSH on proliferation and apoptosis during testis maturation. J Endocrinol 2005; 186(3):429–446.PubMedCrossRefGoogle Scholar
  90. 90.
    Anway MD, Show MD, Zirkin BR. Protein C inhibitor expression by adult rat Sertoli cells: Effects of testosterone withdrawal and replacement. J Androl 2005; 26(5):578–585.PubMedCrossRefGoogle Scholar
  91. 91.
    Denolet E, De Gendt K, Allemeersch J et al. The effect of a Sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Mol Endocrinol 2006; 20:321–334.PubMedCrossRefGoogle Scholar
  92. 92.
    Yamamoto K, Loskutoff DJ. Extrahepatic expression and regulation of protein C in the mouse. Am J Pathol 1998; 153(2):547–555.PubMedGoogle Scholar
  93. 93.
    Odet F, Vérot A, Le Magueresse-Battistoni B. The mouse testis is the source of various serine proteases and SERine Proteinase INhibitors (SERPINs). Serine proteases and SERPINs identified in Leydig cells are under gonadotropin regulation. Endocrinology 2006; 147(9):4374–83.PubMedCrossRefGoogle Scholar
  94. 94.
    Charron Y, Madani R, Nef S et al. Expression of Serpinb6 serpins in germ and somatic cells of mouse gonads. Mol Reprod Dev 2006; 73(1):9–19.PubMedCrossRefGoogle Scholar
  95. 95.
    Honda A, Yamagata K, Sugiura S et al. A mouse serine protease TESP5 is selectively included into lipid rafts of sperm membrane presumably as a glycosylphosphatidylinositol-anchored protein. J Biol Chem 2002; 277(19):16976–16984.PubMedCrossRefGoogle Scholar
  96. 96.
    Takano N, Matsui H, Takahashi T. TESSP-1: A novel serine protease gene expressed in the spermatogonia and spermatocytes of adult mouse testes. Mol Reprod Dev 2005; 70(1):1–10.PubMedCrossRefGoogle Scholar
  97. 97.
    Poorafshar M, Hellman L. Cloning and structural analysis of leydin, a novel human serine protease expressed by the Leydig cells of the testis. Eur J Biochem 1999; 261(1):244–250.PubMedCrossRefGoogle Scholar
  98. Matsui H, Moriyama A, Takahashi T. Cloning and characterization of mouse klk27, a novel tissue kallikrein expressed in, testicular Leydig cells and exhibiting chymotrypsin-like specificity. Eur J Biochem 2000; 267(23):6858–6865.PubMedCrossRefGoogle Scholar
  99. 99.
    Matsui H, Takahashi T. Mouse testicular Leydig cells express Klk21, a tissue kallikrein that cleaves fibronectin and IGF-binding protein-3. Endocrinology 2001; 142:4918–4929.PubMedCrossRefGoogle Scholar
  100. 100.
    Matsui H, Takano N, Takahashi T. Characterization of mouse glandular kallikrein 24 expressed in testicular Leydig cells. Int J Biochem Cell Biol 2005; 37(11):2333–2343.PubMedCrossRefGoogle Scholar
  101. 101.
    Cheng CY, Grima J, Stahler MS et al. Sertoli cell synthesizes and secretes a protease inhibitor, α2-macroglobulin. Biochemistry 1990; 29(4):1063–1068.PubMedCrossRefGoogle Scholar
  102. 102.
    Gettins PG. Thiol ester cleavage-dependent conformational change in human α2-macroglobulin. Influence of attacking nucleophile and of Cys949 modification. Biochemistry 1995; 34(38):12233–12240.PubMedCrossRefGoogle Scholar
  103. 103.
    Stahler MS, Schlegel P, Bardin CW et al. Alpha 2-macroglobulin is not an acute-phase protein in the rat testis. Endocrinology 1991; 128(6):2805–2814.PubMedCrossRefGoogle Scholar
  104. 104.
    Powers CJ, McLeskey SW, Wellistein A. Fibroblast growth factors, their receptors and signalling. Endocr Relat Cancer 2000; 7(3):165–197.PubMedCrossRefGoogle Scholar
  105. 105.
    Loveland KL, Hime G. TGFbeta superfamily members in spermatogenesis: Setting the stage for fertility in mouse and Drosophila. Cell Tissue Res 2005; 322(1):141–146.PubMedCrossRefGoogle Scholar
  106. 106.
    Catizone A, Ricci G, Arista V et al. Hepatocyte growth factor and c-MET are expressed in rat prepuberal testis. Endocrinology 1999; 140(7):3106–3113.PubMedCrossRefGoogle Scholar
  107. 107.
    Catizone A, Ricci G, Galdieri M. Expression and functional role of hepatocyte growth factor receptor (C-MET) during postnatal rat testis development. Endocrinology 2001; 142(5):1828–1834.PubMedCrossRefGoogle Scholar
  108. 108.
    Wajih N, Walter J, Sane DC. Vascular origin of a soluble truncated form of the hepatocyte growth factor (c-met). Circ Res 2002; 90(1):46–52.PubMedCrossRefGoogle Scholar
  109. 109.
    Levi E, Fridman R, Hiao HQ et al. Matrix metalloproteinase 2 releases active soluble ectodomain of fibroblast growth factor receptor 1. Proc Natl Acad Sci USA 1996; 93(14):1069–7074.CrossRefGoogle Scholar
  110. 110.
    Dym M. Basement membrane regulation of Sertoli cells. Endocr Rev 1994; 15(1):102–115.PubMedGoogle Scholar
  111. 111.
    de Kretser DM, Kerr JB, Paulsen CA. The peritubular tissue in the normal and pathological human testis. An ultrastructural study. Biol Reprod 1975; 12(3):317–324.PubMedCrossRefGoogle Scholar
  112. 112.
    Aksglaede L, Wikstrom AM, Rajpert-De Meyts E et al. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod 2006; 12(1):39–48.Google Scholar
  113. 113.
    Anderson R, Fassler R, Georges-Labouesse E et al. Mouse primordial germ cells lacking betal integrins enter the germline but fail to migrate normally to the gonads. Development 1999; 126(8):1655–1664.PubMedGoogle Scholar
  114. 114.
    De Felici M, Scaldaferri ML, Farini D. Adhesion molecules for mouse primordial germ cells. Front Biosci 2005; 10:542–551.PubMedCrossRefGoogle Scholar
  115. 115.
    Pelliniemi LJ, Paranko J, Grund SK et al. Extracellular matrix in testicular differentiation. Ann NY Acad Sci 1984; 438:405–416.PubMedCrossRefGoogle Scholar
  116. 116.
    Magre S, Jost A. Dissociation between testicular organogenesis and endocrine cytodifferentiation of Sertoli cells Proc Natl Acad Sci USA 1984; 81(24):7831–7834.PubMedCrossRefGoogle Scholar
  117. 117.
    Kuopio T, Paranko J, Pelliniemi LJ. Basement membrane and epithelial features of fetal-type Leydig cells in rat and human testis. Differentiation 1989; 40(3):198–206.PubMedCrossRefGoogle Scholar
  118. 118.
    Kanai Y, Hayashi Y, Kawakami H et al. Effect of tunicamycin, an inhibitor of protein glycosylation, on testicular cord organization in fetal mouse gonadal explants in vitro. Anat Rec 1991; 230(2):199–208.PubMedCrossRefGoogle Scholar
  119. 119.
    Mackay S. Gonadal development in mammals at the cellular and molecular levels. Int Rev Cytol 2000; 200:47–99.PubMedCrossRefGoogle Scholar
  120. 120.
    Merchant-Larios H, Moreno-Mendoza N, Buehr M. The role of the mesonephros in cell differentiation and morphogenesis of the mouse fetal testis. Int J Dev Biol 1993; 37(3):407–415.PubMedGoogle Scholar
  121. 121.
    Capel B. The battle of the sexes. Mech Dev 2000; 92(1):89–103.PubMedCrossRefGoogle Scholar
  122. 122.
    Paranko J. Expression of type I and III collagen during morphogenesis of fetal rat testis and ovary. Anat Rec 1987; 219(1):91–101.PubMedCrossRefGoogle Scholar
  123. 123.
    Frojdman K, Paranko J, Kuopio T et al. Structural proteins in sexual differentiation of embryonic gonads. Int J Dev Biol 1989; 33(1):99–103.PubMedGoogle Scholar
  124. 124.
    Fridmacher V, Locquet O, Magre S. Differential expression of acidic cytokeratins 18 and 19 during sexual differentiation of the rat gonad. Development 1992; 115(2):503–517.PubMedGoogle Scholar
  125. 125.
    Frojdman K, Paranko J, Virtanen I et al. Intermediate filaments and epithelial differentiation of male rat embryonic gonad. Differentiation 1992; 50(2):113–123.PubMedCrossRefGoogle Scholar
  126. 126.
    Pelliniemi LJ, Frojdman K. Structural and regulatory macromolecules in sex differentiation of gonads. J Exp Zool 2001; 290(5):523–528.PubMedCrossRefGoogle Scholar
  127. 127.
    Griffin JK, Blecher SR. Extracellular matrix abnormalities in testis and epididymis of XXSxr (“sex-reversed”) mice. Mol Reprod Dev 1994; 38(1):1–7.PubMedCrossRefGoogle Scholar
  128. 128.
    Perera EM, Martin H, Seeherunvong T et al. Tescalcin, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, Col9a3, and renin are expressed in the mouse testis during the early stages of gonadal differentiation. Endocrinology 2001; 142(1):455–163.PubMedCrossRefGoogle Scholar
  129. 129.
    Mazaud S, Guyot R, Guigon CJ et al. Basal membrane remodeling during follicle histogenesis in the rat ovary: Contribution of proteinases of the MMP and PA families. Dev Biol 2005; 277(2):403–416.PubMedCrossRefGoogle Scholar
  130. 130.
    Nef S, Schaad O, Stallings NR et al. Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development. Dev Biol 2005; 287(2):361–377.PubMedCrossRefGoogle Scholar
  131. 131.
    Beverdam A, Koopman P. Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes. Hum Mol Genet 2006; 15(3):417–431.PubMedCrossRefGoogle Scholar
  132. 132.
    Bitgood MJ, Shen L, McMahon AP. Sertoli cell signaling by Desert hedgehog regulates the male germline. Curr Biol 1996; 6(3):298–304.PubMedCrossRefGoogle Scholar
  133. 133.
    Clark AM, Garland KK, Russell LD. Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biol Reprod 2000; 63(6):1825–1838.PubMedCrossRefGoogle Scholar
  134. 134.
    Pierucci-Alves F, Clark AM, Russell LD. A developmental study of the Desert hedgehog-null mouse testis. Biol Reprod 2001; 65(5):1392–1402.PubMedCrossRefGoogle Scholar
  135. 135.
    Yao HH, Capel B. Disruption of testis cords by cyclopamine or forskolin reveals independent cellular pathways in testis organogenesis. Dev Biol 2002; 246(2):356–365.PubMedCrossRefGoogle Scholar
  136. 136.
    Tung PS, Burdzy K, Fritz IB. Proteases are implicated in the changes in the Sertoli cell cytoskeleton elicited by follicle-stimulating hormone or by dibutyryl cyclic AMP. J Cell Physiol 1993; 155(1):139–148.PubMedCrossRefGoogle Scholar
  137. 137.
    Skinner MK, Tung PS, Fritz IB. Cooperativity between Sertoli cells and testicular peritubular cells in the production and deposition of extracellular matrix components. J Cell Biol 1985; 100(6):1941–1947.PubMedCrossRefGoogle Scholar
  138. 138.
    Hadley MA, Weeks BS, Kleinman HK et al. Laminin promotes formation of cord-like structures by Sertoli cells in vitro. Dev Biol 1990; 40(2):318–327.CrossRefGoogle Scholar
  139. 139.
    Tung PS, Fritz IB. Role of laminin in the morphogenetic cascade during coculture of Sertoli cells with peritubular cells. J Cell Physiol 1994; 161(1):77–88.PubMedCrossRefGoogle Scholar
  140. 140.
    van der Wee K, Hofmann MC. An in vitro tubule assay identifies HGF as a morphogen for the formation of seminiferous tubules in the postnatal mouse testis. Exp Cell Res 1999; 252(1):175–185.PubMedCrossRefGoogle Scholar
  141. 141.
    Hager M, Gawlik K, Nystrom A et al. Laminin {alpha}1 chain corrects male infertility caused by absence of laminin {alpha}2 chain. Am J Pathol 2005; 167(3):823–833.PubMedGoogle Scholar
  142. 142.
    Lui WY, Mruk D, Lee WM et al. Sertoli cell tight junction dynamics: Their regulation during spermatogenesis. Biol Reprod 2003; 68(4):1087–1097.PubMedCrossRefGoogle Scholar
  143. 143.
    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.PubMedCrossRefGoogle Scholar
  144. 144.
    Penttila TL, Kaipia A, Toppari J et al. Localization of urokinase-and tissue-type plasminogen activator mRNAs in rat testes. Mol Cell Endocrinol 1994; 105(1):55–64.PubMedCrossRefGoogle Scholar
  145. 145.
    Toppari J, Vihko KK, Rasanen KG et al. Regulation of stages VI and VIII of the rat seminiferous epithelial cycle in vitro. J Endocrinol 1986; 108(3):417–422.PubMedCrossRefGoogle Scholar
  146. 146.
    Zhu LJ, Cheng CY, Phillips DM et al. The immunohistochemical localization of alpha 2-macro-globulin in rat testes is consistent with its role in germ cell movement and spermiation. J Androl 1994; 15:575–582.PubMedGoogle Scholar
  147. 147.
    Mruk D, Zhu LJ, Silvestrini B et al. Interactions of proteases and protease inhibitors in Sertoli-germ cell cocultures preceding the formation of specialized Sertoli-germ cell junctions in vitro. J Androl 1997; 18(6):612–622.PubMedGoogle Scholar
  148. 148.
    Wright WW, Zabludoff SD, Penttila TL et al. Germ cell-Sertoli cell interactions: Regulation by germ cells of the stage-specific expression of CP-2/cathepsin L mRNA by Sertoli cells. Dev Genet 1995; 16(2):104–113.PubMedCrossRefGoogle Scholar
  149. 149.
    Zabludoff SD, Charron M, DeCerbo JN et al. Male germ cells regulate transcription of the cathepsin 1 gene by rat Sertoli cells. Endocrinology 2001; 142(6):2318–2327.PubMedCrossRefGoogle Scholar
  150. 150.
    Braghiroli L, Silvestrini B, Sorrentino C et al. Regulation of alpha2-macroglobulin expression in rat Sertoli cells and hepatocytes by germ cells in vitro. Biol Reprod 1998; 59(1):111–123.PubMedCrossRefGoogle Scholar
  151. 151.
    Wong CC, Chung SS, Grima J et al. Changes in the expression of junctional and nonjunctional complex component genes when inter-Sertoli tight junctions are formed in vitro. J Androl 2000; 21(2):227–237.PubMedGoogle Scholar
  152. 152.
    Mruk D, Cheng CY. Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev 2004; 25(5):747–806.PubMedCrossRefGoogle Scholar
  153. 153.
    Regaud C. Etudes sur la structure des tubes séminifères et sur la spermatogenèse chez les mammifères. Arch Anat Microscop Morphol Exp 1901; 4:101–156, 231–280.Google Scholar
  154. 154.
    Roosen_Runge EC. Kinetics of spermatogenesis in mammals. Ann NY Acad Sci 1952; 55(4):574–584.PubMedCrossRefGoogle Scholar
  155. 155.
    Sigillo F, Pernod G, Kolodie L et al. Residual bodies stimulate rat Sertoli cell plasminogen activator activity. Biochem Biophys Res Commun 1998; 250(1):59–62.PubMedCrossRefGoogle Scholar
  156. 156.
    Pineau C, Le Magueresse B, Courtens JL et al. Study in vitro of the phagocytic function of Sertoli cells in the rat. Cell Tissue Res 1991; 264(3):589–598.PubMedCrossRefGoogle Scholar
  157. 157.
    Gerard N, Syed V, Jegou B. Lipopolysaccharide, latex beads and residual bodies are potent activators of Sertoli cell interleukin-1 alpha production. Biochem Biophys Res Commun 1992; 185(1):154–161.PubMedCrossRefGoogle Scholar
  158. 158.
    Syed V, Stephan JP, Gerard N et al. Residual bodies activate Sertoli cell interleukin-1α (IL-1α) release, which triggers IL-6 production by an autocrine mechanism, through the lipoxygenase pathway. Endocrinology 1995; 136(7):3070–3078.PubMedCrossRefGoogle Scholar
  159. 159.
    Sharpe RM, Maddocks S, Millar M et al. Testosterone and spermatogenesis. Identification of stage-specific, androgen-regulated proteins secreted by adult rat seminiferous tubules. J Androl 1992; 13(2):172–184.PubMedGoogle Scholar
  160. 160.
    O’Donnell L, McLachlan RI, Wreford NG et al. Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium. Biol Reprod 1996; 55(4):895–901.PubMedCrossRefGoogle Scholar
  161. 161.
    Zirkin BR. Spermatogenesis: Its regulation by testosterone and FSH. Semin Cell Dev Biol 1998 9(4):417–421.PubMedCrossRefGoogle Scholar
  162. 162.
    Hill CM, Anway MD, Zirkin BR et al. Intratesticular androgen levels, androgen receptor localization, and androgen receptor expression in adult rat Sertoli cells. Biol Reprod 2004; 71(4):1348–1358.PubMedCrossRefGoogle Scholar
  163. 163.
    Ailenberg M, McCabe D, Fritz IB. Androgens inhibit plasminogen activator activity secreted by Sertoli cells in culture in a two-chambered assembly. Endocrinology 1990; 126(3):1561–1568.PubMedCrossRefGoogle Scholar
  164. 164.
    Uhrin P, Dewerchin M, Hilpert M et al. Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility. J Clin Invest 2000; 106(12): 1531–1539.PubMedCrossRefGoogle Scholar
  165. 165.
    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(6):649–659.PubMedCrossRefGoogle Scholar
  166. 166.
    Meng J, Holdcraft RW, Shima JE et al. Androgens regulate the permeability of the blood-testis barrier. Proc. Natl Acad Sci USA 2005; 102(46):16696–16700.PubMedCrossRefGoogle Scholar
  167. 167.
    Gye MC. Changes in the expression of claudins and transepithelial electrical resistance of mouse Sertoli cells by Leydig cell coculture. Int J Androl 2003; 26:271–278.PubMedCrossRefGoogle Scholar
  168. 168.
    Florin A, Maire M, Bozec A et al. Androgens and postmeiotic germ cells regulate claudin-11 expression rat Sertoli cells. Endocrinology 2005; 146(3):1532–1540.PubMedCrossRefGoogle Scholar
  169. 169.
    Miyamori H, Takino T, Kobayashi Y et al. Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. J Biol Chem 2001; 276(30):28204–28211.PubMedCrossRefGoogle Scholar
  170. 170.
    Diaz ES, Pellizzari E, Meroni S et al. Effect of extracellular matrix proteins on in vitro testosterone production by rat Leydig cells. Mol Reprod Dev 2002; 61(4):493–503.PubMedCrossRefGoogle Scholar
  171. 171.
    Diaz ES, Pellizzari E, Casanova M et al. Type IV collagen induces downregulation of steroidogenic response to gonadotropins in adult rat Leydig cells involving mitogen-activated protein kinase. Mol Reprod Dev 2005; 72(2):208–215.PubMedCrossRefGoogle Scholar
  172. 172.
    Leask A, Abraham DJ. TGF-β signaling and the fibrotic response. FASEB J 2004; 18(7):816–827.PubMedCrossRefGoogle Scholar
  173. 173.
    Dickson C, Webster DR, Johnson H et al. Transforming growth factor-β effects on morphology of immature rat Leydig cells. Mol Cell Endocrinol 2002; 195(1–2):65–77.PubMedCrossRefGoogle Scholar
  174. 174.
    Gnessi L, Fabbri A, Spera G. Gonadal peptides as mediators of development and functional control of the testis: An integrated system with hormones and local environment. Endocr Rev 1997; 18(4):541–609.PubMedCrossRefGoogle Scholar
  175. 175.
    Carmeliet P, Kieckens L, Schoonjans L et al. Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by homologous recombination and characterization. J Clin Invest 1993; 92(6):2746–2755.PubMedCrossRefGoogle Scholar
  176. 176.
    Nothnick WB, Soloway PD, Curry TEJ. Pattern of messenger ribonucleic acid expression of tissue inhibitors of metalloproteinases (TIMPs) during testicular maturation in male mice lacking a functional TIMP-1 gene. Biol Reprod 1998; 59(2):364–370.PubMedCrossRefGoogle Scholar
  177. 177.
    Wright WW, Smith L, Kerr C et al. Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis. Biol Reprod 2003; 68:680–687.PubMedCrossRefGoogle Scholar
  178. 178.
    Holmbeck K, Bianco P, Caterina J et al. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 1999; 99(1):81–92.PubMedCrossRefGoogle Scholar
  179. 179.
    Murer V, Spetz JF, Hengst U et al. Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1. Proc Natl Acad Sci USA 2001; 98(6):3029–3033.PubMedCrossRefGoogle Scholar
  180. 180.
    Toyama Y, Maekawa M, Kadomatsu K et al. Histological characterization of defective spermatogenesis in mice lacking the basigin gene. Anat Histol Embryol 1999; 28:205–213.PubMedCrossRefGoogle Scholar
  181. 181.
    Maekawa M, Suzuki-Toyota F, Toyama Y et al. Stage-specific localization of basigin, a member of the immunoglobulin superfamily, during mouse spermatogenesis. Arch Histol Cytol 1998; 61(5):405–415.PubMedCrossRefGoogle Scholar
  182. 182.
    Li SW, Arita M, Fertala A et al. Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility. Biochem J 2001; 355(Pt 2):271–278.PubMedCrossRefGoogle Scholar
  183. 183.
    Rudolph-Owen LA, Cannon P, Matrisian LM. Overexpression of the matrix metalloproteinase matrilysin results in premature mammary gland differentiation and male infertility. Mol Biol Cell 1998; 9:421–435.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Inserm U418 and INRA UMR 1245 and Université Lyon 1Hopital DebrousseLyon cedex 05France

Personalised recommendations