Connexins in the male reproductive system

Connexins: A Guide

Volumn , Issue , 2009, Pages 495-510

  Pointis, Georges ^a   Fiorini, Céline ^a   Gilleron, Jérome ^a   Carette, Diane ^a   Segretain, Dominique ^a  

^a INSERM   (France)

Author keywords

Cx26; Cx30.2; Cx31; Cx31.1; Cx32; Cx33; Cx37; Cx40; Cx43; Cx46; Cx50; Erectile dysfunction; Male infertility; Male reproductive tract; Testicular cancer; Testis

Indexed keywords

EID: 84920103809     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-59745-489-6_25     Document Type: Chapter

References (101)

1. Griswold M. Protein secretion by Sertoli cells: General consideration. In: Russell LD, Griswold MD, editors. Clearwater: Cache River Press; 1993. pp. 195-200.
2. Hughes IA, Lim HN, Martin H, Mongan NP, Dovey L, Ahmed SF, Hawkins JR. Developmental aspects of androgen action. Mol Cell Endocrinol. 2001;185:33-41.
3. Zhang JT, Nicholson BJ. Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx26, as deduced from its cDNA. J Cell Biol. 1989;109:3391-401.
4. Kadle R, Zhang JT, Nicholson BJ. Tissue-specific distribution of differentially phosphorylated forms of Cx43. Mol Cell Biol. 1991;11:363-9.
5. Haefliger JA, Bruzzone R, Jenkins NA, Gilbert DJ, Copeland NG, Paul DL. Four novel members of the connexin family of gap junction proteins. Molecular cloning, expression, and chromosome mapping. J Biol Chem. 1992;267:2057-64.
6. Hennemann H, Dahl E, White JB, Schwarz HJ, Lalley PA, Chang S, Nicholson BJ, Willecke K. Two gap junction genes, connexin 31.1 and 30.3, are closely linked on mouse chromosome 4 and preferentially expressed in skin. J Biol Chem. 1992;267:17225-33.
7. Risley MS. Connexin gene expression in seminiferous tubules of the Sprague-Dawley rat. Biol Reprod. 2000;62:748-54.
8. Nielsen PA, Kumar NM. Differences in expression patterns between mouse connexin-30.2 (Cx30.2) and its putative human orthologue, connexin-31.9. FEBS Lett. 2003;540:151-6.
9. Juneja SC. mRNA expression pattern ofmultiplemembers of connexin gene family in normal and abnormal fetal gonads in mouse. Indian J Physiol Pharmacol. 2003;47:147-56.
10. Risley MS, Tan IP, Roy C, Sá ez JC. Cell-, age- and stage-dependent distribution of connexin43 gap junctions in testes. J Cell Sci. 1992;103:81-96.
11. Varanda WA, de Carvalho AC. Intercellular communication between mouse Leydig cells. Am J Physiol. 1994;267:C563-9.
12. Pelletier RM. The distribution of connexin 43 is associated with the germ cell differentiation and with the modulation of the Sertoli cell junctional barrier in continual (guinea pig) and seasonal breeders' (mink) testes. J Androl. 1995;16:400-9.
13. Batias C, Defamie N, Lablack A, Thepot D, Fenichel P, Segretain D, Pointis G. Modified expression of testicular gap-junction connexin 43 during normal spermatogenic cycle and in altered spermatogenesis. Cell Tissue Res. 1999;298:113-21.
14. Batias C, Siffroi JP, Fenichel P, Pointis G, Segretain D. Connexin43 gene expression and regulation in the rodent seminiferous epithelium. J Histochem Cytochem. 2000;48:793-805.
15. Palmiero C, Ferrara D, De Rienzo G, d'Istria M, Minucci S. Ethane 1, 2-dimethane sulphonate is a useful tool for studying cell-to-cell interactions in the testis of the frog, Rana esculenta. Gen Comp Endocrinol. 2003;131:38-47.
16. Steger K, Tetens F, Bergmann M. Expression of connexin 43 in human testis. Histochem Cell Biol. 1999;112:215-20.
17. Defamie N, Berthaut I, Mograbi B, Chevallier D, Dadoune JP, Fenichel P, Segretain D, Pointis G. Impaired gap junction connexin43 in Sertoli cells of patients with secretory azoospermia: a marker of undifferentiated Sertoli cells. Lab Invest. 2003;83:449-56.
18. Segretain D, Chevallier D, Fenichel P, Pointis G. Gap junction connexin 43 expression in human normal germ cells and testicular seminoma cells. Trends Reprod Biol. 2005;1:49-55.
19. Risley MS, Tan IP, Farrell J. Gap junctions with varied permeability properties establish cell-type specific communication pathways in the rat seminiferous epithelium. Biol Reprod. 2002;67:945-52.
20. Decrouy X, Gasc JM, Pointis G, Segretain D. Functional characterization of Cx43 based gap junctions during spermatogenesis. J Cell Physiol. 2004;200:146-54.
21. Mok BW, Yeung WS, Luk JM. Differential expression of gap-junction gene connexin 31 in seminiferous epithelium of rat testes. FEBS Lett. 1999;453:243-48.
22. Cheng S, Shakespeare T, Mui R, White TW, Valdimarsson G. Connexin 48.5 is required for normal cardiovascular function and lens development in zebrafish embryos. J Biol Chem. 2004;279:36993-37003.
23. Batlouni SR, Carreno FR, Romagosa E, Borella MI. Cell junctions in the germinal epithelium may play an important role in spermatogenesis of the catfish P. fasciatum (Pisces, Siluriformes). J Mol Histol. 2005;36:97-110.
24. Tan IP, Roy C, Sá ez JC, Sá ez CG, Paul DL, Risley MS. Regulated assembly of connexin33 and connexin43 into rat Sertoli cell gap junctions. Biol Reprod. 1996;54:1300-10.
25. Fiorini C, Mograbi B, Cronier L, Bourget I, Decrouy X, Nebout M, Ferrua B, Malassine A, Samson M, Fenichel P, Segretain D, Pointis G. Dominant-negative effect of connexin33 on gap junctional communication is mediated by connexin43 sequestration. J Cell Sci. 2004;117:4665-72.
26. Fischer P, Brehm R, Konrad L, Hartmann S, Kliesch S, Bohle RM, BergmannM. Connexin 33: a rodent-specific member of the gap junction protein family? J Androl. 2005;26:75-84.
27. Chung SS, Lee WM, Cheng CY. Study on the formation of specialized inter-Sertoli cell junctions in vitro. J Cell Physiol. 1999;181:258-72.
28. Chang M, Werner R, Dahl G. A role for an inhibitory connexin in testis? Dev Biol. 1996;175:50-6.
29. Brehm R, Marks A, Rey R, Kliesch S, Bergmann M, Steger K. Altered expression of connexins 26 and 43 in Sertoli cells in seminiferous tubules infiltrated with carcinoma-insitu or seminoma. J Pathol. 2002;197:647-53.
30. White TW, Srinivas M, Ripps H, Trovato-Salinaro A, Condorelli DF, Bruzzone R. Virtual cloning, functional expression, and gating analysis of human connexin31.9. Am J Physiol Cell Physiol. 2002;283:C960-70.
31. Okada K, Katagiri T, Tsunoda T, Mizutani Y, Suzuki Y, Kamada M, Fujioka T, Shuin T, Miki T, Nakamura Y. Analysis of gene-expression profiles in testicular seminomas using a genome-wide cDNA microarray. Int J Oncol. 2003;23:1615-35.
32. Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M, Deutsch U, Söhl G. Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem. 2002;383:725-37.
33. You S, Li W, Lin T. Expression and regulation of connexin43 in rat Leydig cells. J Endocrinol. 2000;166:447-53.
34. Goldenberg RC, Fortes FS, Cristancho JM, Morales MM, Franci CR, Varanda WA, Campos de Carvalho AC. Modulation of gap junction mediated intercellular communication in M3 Leydig cells. J Endocrinol. 2003;177:327-35.
35. Cristancho JM, Campos de Carvalho AC, Varanda WA. Short term regulation of cell-cell communication in M3 Leydig cells. A perforated patch study. Biochim Biophys Acta. 2000;1496:325-32.
36. Bravo-Moreno JF, Diaz-Sanchez V, Montoya-Flores JG, Lamoyi E, Sá ez JC, Perez-Armendariz EM. Expression of connexin43 in mouse Leydig, Sertoli, and germinal cells at different stages of postnatal development. Anat Rec. 2001;264:13-24.
37. Perez-Armendariz EM, Lamoyi E, Mason JI, Cisneros-Armas D, Luu-The V, Bravo Moreno JF. Developmental regulation of connexin 43 expression in fetal mouse testicular cells. Anat Rec. 2001;264:237-46.
38. Lablack A, Bourdon V, Defamie N, Batias C, Mesnil M, Fenichel P, Pointis G, Segretain D. Ultrastructural and biochemical evidence for gap junction and connexin 43 expression in a clonal Sertoli cell line: a potential model in the study of junctional complex formation. Cell Tissue Res. 1998;294:279-87.
39. Pluciennik F, Joffre M, Deleze J. Follicle-stimulating hormone increases gap junction communication in Sertoli cells from immature rat testis in primary culture. J Membr Biol. 1994;139:81-96.
40. Herve JC, Pluciennik F, Bastide B, Cronier L, Verrecchia F, Malassine A, Joffre M, Deleze J. Contraceptive gossypol blocks cell-to-cell communication in human and rat cells. Eur J Pharmacol. 1996;313:243-55.
41. Pluciennik F, Verrecchia F, Bastide B, Herve JC, Joffre M, Deleze J. Reversible interruption of gap junctional communication by testosterone propionate in cultured Sertoli cells and cardiac myocytes. J Membr Biol. 1996;149:169-77.
42. Hess RA, Cooke PS, Bunick D, Kirby JD. Adult testicular enlargement induced by neonatal hypothyroidism is accompanied by increased Sertoli and germ cell numbers. Endocrinology 1993;132:2607-13.
43. St-Pierre N, Dufresne J, Rooney AA, Cyr DG. Neonatal hypothyroidism alters the localization of gap junctional protein connexin 43 in the testis and messenger RNA levels in the epididymis of the rat. Biol Reprod. 2003;68:1232-40.
44. Gilleron J, Nebout M, Scarabelli L, Senegas-Balas F, Palmero S, Segretain D, Pointis G. Apotential novel mechanism involving connexin 43 gap junction for control of Sertoli cell proliferation by thyroid hormones. J Cell Physiol. 2006;209:153-61.
45. Luk JM, Mok BW, Shum CK, Yeung WS, Tam PC, Tse JY, Chow JF, Woo J, Kam K, Lee KF. Identification of novel genes expressed during spermatogenesis in stagesynchronized rat testes by differential display. Biochem Biophys Res Commun. 2003;307:782-90.
46. Fiorini C, Decrouy X, Defamie N, Segretain D, Pointis G. Opposite regulation of connexin33 and connexin43 by LPS and IL-1α in spermatogenesis. Am J Physiol Cell Physiol. 2006;290:C733-40.
47. Xu X, Li WE, Huang GY, Meyer R, Chen T, Luo Y, Thomas MP, Radice GL, Lo CW. Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions. J Cell Biol. 2001;154:217-30.
48. Wei CJ, Xu X, Lo CW. Connexins and cell signaling in development and disease. Annu Rev Cell Dev Biol. 2004;20:811-38.
49. Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem. 2002;277:8648-57.
50. Qin H, Shao Q, Curtis H, Galipeau J, Belliveau DJ, Wang T, Alaoui-Jamali MA, Laird DW. Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication. J Biol Chem. 2002;277:29132-8.
51. Qin H, Shao Q, Thomas T, Kalra J, Alaoui-Jamali MA, Laird DW. Connexin26 regulates the expression of angiogenesis-related genes in human breast tumor cells by both GJICdependent and -independent mechanisms. Cell Commun Adhes. 2003;10:387-93.
52. Reaume AG, de Sousa PA, Kulkarni S, Langille BL, Zhu D, Davies TC, Juneja SC, Kidder GM, Rossant J. Cardiac malformation in neonatal mice lacking connexin43. Science. 1995;267:1831-4.
53. Juneja SC, Barr KJ, Enders GC, Kidder GM. Defects in the germ line and gonads of mice lacking connexin43. Biol Reprod. 1999;60:1263-70.
54. Roscoe WA, Barr KJ, Mhawi AA, Pomerantz DK, Kidder GM. Failure of spermatogenesis in mice lacking connexin43. Biol Reprod. 2001;65:829-38.
55. Tazuke SI, Schulz C, Gilboa L, Fogarty M, Mahowald AP, Guichet A, Ephrussi A, Wood CG, Lehmann R, Fuller MT. A germline-specific gap junction protein required for survival of differentiating early germ cells. Development 2002;129:2529-39.
56. Plum A, Hallas G, Magin T, Dombrowski F, Hagendorff A, Schumacher B, Wolpert C, Kim J, Lamers WH, Evert M, Meda P, Traub O, Willecke K. Unique and shared functions of different connexins in mice. Curr Biol. 2000;10:1083-91.
57. Sridharan S, Simon L, Meling DD, Cyr DG, Gutstein DE, Fishman GI, Guillou F, Cooke PS. Proliferation of adult Sertoli cells following conditional knockout of the gap junctional protein GJA1 (Connexin 43). Biol Reprod. 2007;76:804-12.
58. Lee NP, Leung KW, Wo JY, Tam PC, Yeung WS, Luk JM. Blockage of testicular connexins induced apoptosis in rat seminiferous epithelium. Apoptosis. 2006;11:1215-29.
59. Nelles E, Butzler C, Jung D, Temme A, Gabriel HD, Dahl U, Traub O, Stumpel F, Jungermann K, Zielasek J, Toyka KV, Dermietzel R, Willecke K. Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice. Proc Natl Acad Sci USA. 1996;93:9565-70.
60. Simon AM, Goodenough DA, Li E, Paul DL. Female infertility in mice lacking connexin Nature. 1997;385:525-9.
61. Gabriel HD, Jung D, Butzler C, Temme A, Traub O, Winterhager E, Willecke K. Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice. J Cell Biol. 1998;140:1453-61.
62. Kirchhoff S, Nelles E, Hagendorff A, Kruger O, Traub O, Willecke K. Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice. Curr Biol. 1998;8:299-302.
63. Simon AM, Goodenough DA, Paul DL. Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle branch block. Curr Biol. 1998;8:295-8.
64. Plum A, Winterhager E, Pesch J, Lautermann J, Hallas G, Rosentreter B, Traub O, Herberhold C, Willecke K. Connexin31-deficiency in mice causes transient placental dysmorphogenesis but does not impair hearing and skin differentiation. Dev Biol. 2001;231:334-7.
65. van Rijen HV, van Veen TA, van Kempen MJ, Wilms-Schopman FJ, Potse M, Krueger O, Willecke K, Opthof T, Jongsma HJ, de Bakker JM. Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40. Circulation. 2001;103:1591-98.
66. Simon AM, McWhorter AR. Vascular abnormalities in mice lacking the endothelial gap junction proteins connexin37 and connexin40. Dev Biol. 2002;251:206-20.
67. Nagano T, Suzuki F. Freeze-fracture observations on the intercellular junctions of Sertoli cells and of Leydig cells in the human testis. Cell Tissue Res. 1976;166:37-48.
68. Bigliardi E, Vegni-Talluri M. Gap junctions between Sertoli cells in the infertile human testis. Fertil Steril. 1977;28:755-8.
69. Schleiermacher E. Ultrastructural changes of the intercellular relationship in impaired human spermatogenesis. Hum Genet. 1980;54:391-404.
70. Camatini M, Franchi E, de Curtis I, Anelli G, Masera G. Chemotherapy does not affect the development of inter-Sertoli junctions in childhood leukaemia. Anat Rec. 1982;203:353-63.
71. Cavicchia JC, Sacerdote FL, Ortiz L. The human blood-testis barrier in impaired spermatogenesis. Ultrastruct Pathol. 1996;20:211-18.
72. Trosko JE. The role of stem cells and gap junctional intercellular communication in carcinogenesis. J Biochem Mol Biol. 2003;36:43-8.
73. Mesnil M. Connexins and cancer. Biol Cell. 2002;94:493-500.
74. Roger C, Mograbi B, Chevallier D, Michiels JF, Tanaka H, Segretain D, Pointis G, Fenichel P. Disrupted traffic of connexin 43 in human testicular seminoma cells: overexpression of Cx43 induces membrane location and cell proliferation decrease. J Pathol. 2004;202:241-6.
75. Segretain D, Decrouy X, Dompierre J, Escalier D, Rahman N, Fiorini C, Mograbi B, Siffroi JP, Huhtaniemi I, Fenichel P, Pointis G. Sequestration of connexin43 in the early endosomes: an early event of Leydig cell tumor progression. Mol Carcinog. 2003;38:179-87.
76. Jamieson S, Going JJ, D'Arcy R, George WD. Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumors. J Pathol. 1998;184:37-43.
77. Dufresne J, Finnson KW, Gregory M, Cyr DG. Expression of multiple connexins in the rat epididymis indicates a complex regulation of gap junctional communication. Am J Physiol Cell Physiol. 2003;284:C33-43.
78. Cyr DG, Finnson KW, Dufresne J, Gregory M. Cellular interaction and the bloodepididymal barrier. New York: Plenum; 2002. pp. 103-118.
79. Cyr DG, Hermo L, Laird DW. Immunocytochemical localization and regulation of connexin43 in the adult rat epididymis. Endocrinology 1996;137:1474-84.
80. Meda P, Pepper MS, Traub O, Willecke K, Gros D, Beyer E, Nicholson B, Paul D, Orci L. Differential expression of gap junction connexins in endocrine and exocrine glands. Endocrinology. 1993;133:2371-8.
81. Habermann H, Chang WY, Birch L, Mehta P, Prins GS. Developmental exposure to estrogens alters epithelial cell adhesion and gap junction proteins in the adult rat prostate. Endocrinology. 2001;142:359-69.
82. Habermann H, Ray V, Habermann W, Prins GS. Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer. J Urol. 2002;167:655-60.
83. Van der Aa F, Roskams T, Blyweert W, De Ridder D. Interstitial cells in the human prostate: a new therapeutic target? Prostate 2003;56:250-5.
84. Huynh HT, Alpert L, Laird DW, Batist G, Chalifour L, Alaoui-Jamali MA. Regulation of the gap junction connexin 43 gene by androgens in the prostate. J Mol Endocrinol. 2001;26:1-10.
85. Carruba G, Webber MM, Quader ST, Amoroso M, Cocciadiferro L, Saladino F, Trosko JE, Castagnetta LA. Regulation of cell-to-cell communication in nontumorigenic and malignant human prostate epithelial cells. Prostate. 2002;50:73-82.
86. Tsai H, Werber J, Davia MO, Edelman M, Tanaka KE, Melman A, Christ GJ, Geliebter J. Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells. Biochem Biophys Res Commun. 1996;227:64-69.
87. Hossain MZ, Jagdale AB, Ao P, LeCiel C, Huang RP, Boynton AL. Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells. Prostate 1999;38:55-59.
88. Mehta PP, Perez-Stable C, Nadji M, Mian M, Asotra K, Roos BA. Suppression of human prostate cancer cell growth by forced expression of connexin genes. Dev Genet. 1999;24:91-110.
89. Govindarajan R, Zhao S, Song XH, Guo RJ, Wheelock M, Johnson KR, Mehta PP. Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by α-catenin. J Biol Chem. 2002;277:50087-97.
90. Carruba G, Stefano R, Cocciadiferro L, Saladino F, Di Cristina A, Tokar E, Quader ST, Webber MM, Castagnetta L. Intercellular communication and human prostate carcinogenesis. Ann NY Acad Sci. 2002;963:156-68.
91. Saladino F, Carruba G, Quader ST, Amoroso M, Di Cristina A, Webber MM, Castagnetta LA. Connexin expression in nonneoplastic human prostate epithelial cells. Ann NY Acad Sci. 2002;963:213-7.
92. Tanaka M, Grossman HB. Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells. Oncol Rep. 2004;11:537-41.
93. Fukushima M, Hattori Y, Yoshizawa T, Maitani Y. Combination of non-viral connexin 43 gene therapy and docetaxel inhibits the growth of human prostate cancer in mice. Int J Oncol. 2007;30:225-31.
94. Christ GJ, Moreno AP, Parker ME, Gondre CM, Valcic M, Melman A, Spray DC. Intercellular communication through gap junctions: a potential role in pharmacomechanical coupling and syncytial tissue contraction in vascular smooth muscle isolated from the human corpus cavernosum. Life Sci. 1991;49:PL195-L200.
95. Campos de Carvalho AC, Roy C, Moreno AP, Melman A, Hertzberg EL, Christ GJ, Spray DC. Gap junctions formed of connexin43 are found between smooth muscle cells of human corpus cavernosum. J Urol. 1993;149:1568-75.
96. Pointis G. Connexin43: emerging role in erectile function. Int J Biochem Cell Biol. 2006;38:1642-6.
97. Serels S, Day NS, Wen YP, Giraldi A, Lee SW, Melman A, Christ GJ. Molecular studies of human connexin 43 (Cx43) expression in isolated corporal tissue strips and cultured corporal smooth muscle cells. Int J Impot Res. 1998;10:135-143.
98. Karicheti V, Christ GJ. Physiological roles for K+ channels and gap junctions in urogenital smooth muscle: implications for improved understanding of urogenital function, disease and therapy. Curr Drug Targets. 2001;2:1-20.
99. Brink PR, Valiunas V, Wang HZ, Zhao W, Davies K, Christ GJ. Experimental diabetes alters connexin43 derived gap junction permeability in short-term cultures of rat corporeal vascular smooth muscle cells. J Urol. 2006;175:381-6.
100. Gerido DA, White TW. Connexin disorders of the ear, skin, and lens. Biochim Biophys Acta. 2004;1662:159-70.
101. Pointis G, Segretain D. Role of connexin-based gap junction channels in testis. Trends Endocrinol Metab. 2005;16:300-6.