Sertoli-cell-specific knockout of connexin 43 leads to multiple alterations in testicular gene expression in prepubertal mice

DMM Disease Models and Mechanisms

Volumn 5, Issue 6, 2012, Pages 895-913

  Giese, Sarah ^a   Hossain, Hamid ^a   Markmann, Melanie ^a   Chakraborty, Trinad ^a   Tchatalbachev, Svetlin ^a   Guillou, Florian ^b   Bergmann, Martin ^a   Failing, Klaus ^a   Weider, Karola ^c   Brehm, Ralph ^c  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

^b UNIVERSITÉ DE TOURS   (France)

^c UNIVERSITY OF VETERINARY MEDICINE HANNOVER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CONNEXIN 43;

ANIMAL TISSUE; ANTIGEN PRESENTATION; ARTICLE; CELL DIFFERENTIATION; CELL JUNCTION; CELL MIGRATION; DOWN REGULATION; GAMETOGENESIS; GAP JUNCTION; GENE ACTIVATION; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENOTYPE; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; MALE INFERTILITY; MALE STERILITY; MOUSE; NONHUMAN; PHENOTYPE; PREPUBERTY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; SEMINIFEROUS TUBULE; SERTOLI CELL; SPERMATOCYTE; SPERMATOGENESIS; SPERMATOGONIUM; TESTIS WEIGHT; TRANSGENIC MOUSE; UPREGULATION;

ANIMALS; CELL COUNT; CLUSTER ANALYSIS; CONNEXIN 43; DNA-BINDING PROTEINS; DOWN-REGULATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE KNOCKOUT TECHNIQUES; GENE REGULATORY NETWORKS; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MICE; MICE, KNOCKOUT; MOLECULAR SEQUENCE ANNOTATION; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; ORGAN SPECIFICITY; PROTEIN BIOSYNTHESIS; REAL-TIME POLYMERASE CHAIN REACTION; REPRODUCIBILITY OF RESULTS; SERTOLI CELLS; SEXUAL MATURATION; SPERMATOGENESIS; SPERMATOZOA; TRANSCRIPTION FACTORS; UP-REGULATION;

MUS; MUS MUSCULUS;

EID: 84870040649     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.008649     Document Type: Article

References (123)

1. Anderson, E. L., Baltus, A. E., Roepers-Gajadien, H. L., Hassold, T. J., de Rooij, D. G., van Pelt, A. M. and Page, D. C. (2008). Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proc. Natl. Acad. Sci. USA. 105, 14976-14980.
2. Andersson, A. M., Jørgensen, N., Main, K. M., Toppari, J., Rajpert-De Meyts, E., Leffers, H., Juul, A., Jensen, T. K. and Skakkebaek, N. E. (2008). Adverse trends in male reproductive health: we may have reached a crucial 'tipping point'. Int. J. Androl. 31, 74-80.
3. Asklund, C., Jørgensen, N., Kold Jensen, T. and Skakkebaek, N. E. (2004). Biology and epidemiology of testicular dysgenesis syndrome. BJU Int. 3, 6-11. (Pubitemid 38580908)
4. Ballow, D., Meistrich, M. L., Matzuk, M. and Rajkovic, A. (2006). Sohlh1 is essential for spermatogonial differentiation. Dev. Biol. 294, 161-167.
5. Batias, C., Siffroi, J. P., Fenichel, P., Pointis, G. and Segretain, D. (2000). Connexin43 gene expression and regulation in the rodent seminiferous epithelium. J. Histochem. Cytochem. 48, 793-805. (Pubitemid 30366614)
6. Battke, F., Symons, S. and Nieselt, K. (2010). Mayday - integrative analytics for expression data. BMC Bioinformatics 11, 121.
7. Bellvé, A. R., Cavicchia, J. C., Millette, C. F., O'Brien, D. A., Bhatnagar, Y. M. and Dym, M. (1977). Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization. J. Cell Biol. 74, 68-85. (Pubitemid 8141486)
8. Bergmann, M. and Kliesch, S. (1994). The distribution pattern of cytokeratin and vimentin immunoreactivity in testicular biopsies of infertile men. Anat. Embryol. 190, 515-520. (Pubitemid 24359590)
9. Beyret, E. and Lin, H. (2011). Pinpointing the expression of piRNAs and function of the PIWI protein subfamily during spermatogenesis in the mouse. Dev. Biol. 355, 215-226.
10. Bigliardi, E. and Vegni-Talluri, M. (1977). Gap junctions between Sertoli cells in the infertile human testis. Fertil. Steril. 28, 755-758. (Pubitemid 8149583)
11. Bolstad, B. M., Irizarry, R. A., Astrand, M. and Speed, T. P. (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19, 185-193. (Pubitemid 36181903)
12. Bravo-Moreno, J. F., Diaz-Sanchez, V., Montoya-Flores, J. G., Lamoyi, E., Saez, J. C. and Perez-Armendariz, E. M. (2001). Expression of connexin43 in mouse Leydig, Sertoli, and germinal cells at different stages of postnatal development. Anat. Rec. 264, 13-24.
13. Brazma, A., Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W., Ball, C. A., Causton, H. C. et al. (2001). Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat. Genet. 29, 365-371. (Pubitemid 34326681)
14. Brehm, R., Marks, A., Rey, R., Kliesch, S., Bergmann, M. and Steger, K. (2002). Altered expression of connexins 26 and 43 in Sertoli cells in seminiferous tubules infiltrated with carcinoma-in-situ or seminoma. J. Pathol. 197, 647-653.
15. Brehm, R., Rüttinger, C., Fischer, P., Gashaw, I., Winterhager, E., Kliesch, S., Bohle, R. M., Steger, K. and Bergmann, M. (2006). Transition from preinvasive carcinoma in situ to seminoma is accompanied by a reduction of connexin 43 expression in Sertoli cells and germ cells. Neoplasia 8, 499-509. (Pubitemid 44035334)
16. Brehm, R., Zeiler, M., Ruttinger, C., Herde, K., Kibschull, M., Winterhager, E., Willecke, K., Guillou, F., Lecureuil, C., Steger, K. et al. (2007). A Sertoli cell-specific knockout of connexin43 prevents initiation of spermatogenesis. Am. J. Pathol. 171, 19-31. (Pubitemid 47339223)
17. Breitling, R. and Herzyk, P. (2005). Rank-based methods as a non-parametric alternative of the T-statistic for the analysis of biological microarray data. J. Bioinform. Comput. Biol. 3, 1171-1189. (Pubitemid 41683435)
18. Breitling, R., Armengaud, P., Amtmann, A. and Herzyk, P. (2004). Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS. Lett. 573, 83-92. (Pubitemid 39141040)
19. Bruzzone, R., White, T. W. and Paul, D. L. (1996). Connections with connexins: the molecular basis of direct intercellular signaling. Eur. J. Biochem. 238, 1-27. (Pubitemid 26164180)
20. Carette, D., Weider, K., Gilleron, J., Giese, S., Dompierre, J., Bergmann, M., Brehm, R., Denizot, J. P., Segretain, D. and Pointis, G. (2010). Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility. Dev. Biol. 346, 54-67.
21. Cheng, C. Y. and Mruk, D. D. (2002). Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol. Rev. 82, 825-874.
22. Cheng, C. Y., Wong, E. W., Lie, P. P., Mruk, D. D., Xiao, X., Li, M. W., Lui, W. Y. and Lee, W. M. (2011). Polarity proteins and actin regulatory proteins are unlikely partners that regulate cell adhesion in the seminiferous epithelium during spermatogenesis. Histol. Histopathol. 26, 1465-1474.
23. Cheng, Y., Buffone, M. G., Kouadio, M., Goodheart, M., Page, D. C., Gerton, G. L., Davidson, I. and Wang, P. J. (2007). Abnormal sperm in mice lacking the Taf7l gene. Mol. Cell. Biol. 27, 2582-2589. (Pubitemid 46581349)
24. Childs, A. J., Cowan, G., Kinnell, H. L., Anderson, R. A. and Saunders, P. T. (2011). Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. PLoS ONE 6, e20249.
25. Chung, S. S., Choi, C., Wang, X., Hallock, L. and Wolgemuth, D. J. (2010). Aberrant distribution of junctional complex components in retinoic acid receptor alpha-deficient mice. Microsc. Res. Tech. 73, 583-596.
26. Dai, X., Schonbaum, C., Degenstein, L., Bai, W., Mahowald, A. and Fuchs, E. (1998). The ovo gene required for cuticle formation and oogenesis in flies is involved in hair formation and spermatogenesis in mice. Genes Dev. 12, 3452-3463. (Pubitemid 28520992)
27. Decrouy, X., Gasc, J. M., Pointis, G. and Segretain, D. (2004). Functional characterization of Cx43 based gap junctions during spermatogenesis. J. Cell. Physiol. 200, 146-154. (Pubitemid 38720630)
28. Defamie, N., Berthaut, I., Mograbi, B., Chevallier, D., Dadoune, J. P., Fénichel, P., Segretain, D. and Pointis, G. (2003). Impaired gap junction connexin43 in Sertoli cells of patients with secretory azoospermia: a marker of undifferentiated Sertoli cells. Lab. Invest. 83, 449-456. (Pubitemid 36351006)
29. Dennis, G., Jr, Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C. and Lempicki, R. A. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 4, P3.
30. Derangeon, M., Spray, D. C., Bourmeyster, N., Sarrouilhe, D. and Hervé, J. C. (2009). Reciprocal influence of connexins and apical junction proteins on their expressions and functions. Biochim. Biophys. Acta 1788, 768-778.
31. Diehn, M., Sherlock, G., Binkley, G., Jin, H., Matese, J. C., Hernandez-Boussard, T., Rees, C. A., Cherry, J. M., Botstein, D., Brown, P. O. et al. (2003). SOURCE: a unified genomic resource of functional annotations, ontologies, and gene expression data. Nucleic Acids Res. 31, 219-223. (Pubitemid 36150369)
32. EU Strategic Research Plan (2010). Male reproductive health: its impact in relation to general well-being and low European fertility rates. ESF Science Policy Briefing 40, 1-12.
33. Fink, C., Weigel, R., Hembes, T., Lauke-Wettwer, H., Kliesch, S., Bergmann, M. and Brehm, R. H. (2006). Altered expression of ZO-1 and ZO-2 in Sertoli cells and loss of blood-testis barrier integrity in testicular carcinoma in situ. Neoplasia 8, 1019-1027. (Pubitemid 44936151)
34. Fink, C., Weigel, R., Fink, L., Wilhelm, J., Kliesch, S., Zeiler, M., Bergmann, M. and Brehm, R. (2009). Claudin-11 is over-expressed and dislocated from the blood-testis barrier in Sertoli cells associated with testicular intraepithelial neoplasia in men. Histochem. Cell Biol. 131, 755-764.
35. Fiorini, C., Tilloy-Ellul, A., Chevalier, S., Charuel, C. and Pointis, G. (2004). Sertoli cell junctional proteins as early targets for different classes of reproductive toxicants. Reprod. Toxicol. 18, 413-421. (Pubitemid 38479877)
36. Francis, R., Xu, X., Park, H., Wei, C. J., Chang, S., Chatterjee, B. and Lo, C. (2011). Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics. PLoS ONE 6, e26379.
37. Francis, R. J. and Lo, C. W. (2006). Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation. Development 133, 3451-3460. (Pubitemid 44501847)
38. Franke, F. E., Pauls, K., Rey, R., Marks, A., Bergmann, M. and Steger, K. (2004). Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis. Anat. Embryol. (Berl.) 209, 169-177. (Pubitemid 40100857)
39. Franke, W. W., Grund, C. and Schmid, E. (1979). Intermediate-sized filaments present in Sertoli cells are of the vimentin type. Eur. J. Cell Biol. 19, 269-275. (Pubitemid 9230840)
40. Giepmans, B. N., Verlaan, I. and Moolenaar, W. H. (2001a). Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin. Cell Commun. Adhes. 8, 219-223.
41. Giepmans, B. N., Verlaan, I., Hengeveld, T., Janssen, H., Calafat, J., Falk, M. M. and Moolenaar, W. H. (2001b). Gap junction protein connexin-43 interacts directly with microtubules. Curr. Biol. 11, 1364-1368. (Pubitemid 32835878)
42. Gilleron, J., Carette, D., Durand, P., Pointis, G. and Segretain, D. (2009). Connexin 43 a potential regulator of cell proliferation and apoptosis within the seminiferous epithelium. Int. J. Biochem. Cell Biol. 41, 1381-1390.
43. Gilleron, J., Malassiné, A., Carette, D., Segretain, D. and Pointis, G. (2011). Chemical connexin impairment in the developing gonad associated with offspring infertility. Curr. Med. Chem. 18, 5145-5158.
44. Goodenough, D. A., Goliger, J. A. and Paul, D. L. (1996). Connexins, connexons, and intercellular communication. Annu. Rev. Biochem. 65, 475-502. (Pubitemid 26250617)
45. Graf, M., Brobeil, A., Sturm, K., Steger, K. and Wimmer, M. (2011). 14-3-3 beta in the healthy and diseased male reproductive system. Hum. Reprod. 26, 59-66.
46. Gregory, M., Kahiri, C. N., Barr, K. J., Smith, C. E., Hermo, L., Cyr, D. G. and Kidder, G. M. (2011). Male reproductive system defects and subfertility in a mutant mouse model of oculodentodigital dysplasia. Int. J. Androl. 34, e630-e641.
47. Griswold, M. D. (1995). Interactions between germ cells and Sertoli cells in the testis. Biol. Reprod. 52, 211-216.
48. Gutti, R. K., Tsai-Morris, C. H. and Dufau, M. L. (2008). Gonadotropin-regulated testicular helicase (DDX25), an essential regulator of spermatogenesis, prevents testicular germ cell apoptosis. J. Biol. Chem. 283, 17055-17064.
49. Gwadry, F. G., Sequeira, A., Hoke, G., Ffrench-Mullen, J. M. and Turecki, G. (2005). Molecular characterization of suicide by microarray analysis. Am. J. Med. Genet. C. Semin. Med. Genet. 133C, 48-56.
50. Hartsock, A. and Nelson, W. J. (2008). Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim. Biophys. Acta 1778, 660-669. (Pubitemid 351317795)
51. Hentrich, A., Wolter, M., Szardening-Kirchner, C., Lüers, G. H., Bergmann, M., Kliesch, S. and Konrad, L. (2011). Reduced numbers of Sertoli, germ, and spermatogonial stem cells in impaired spermatogenesis. Mod. Pathol. 24, 1380-1389.
52. Hernandez-Blazquez, F. J., Joazeiro, P. P., Omori, Y. and Yamasaki, H. (2001). Control of intracellular movement of connexins by E-cadherin in murine skin papilloma cells. Exp. Cell. Res. 270, 235-247. (Pubitemid 33030162)
53. Huang, G. Y., Cooper, E. S., Waldo, K., Kirby, M. L., Gilula, N. B. and Lo, C. W. (1998). Gap junction-mediated cell-cell communication modulates mouse neural crest migration. J. Cell Biol. 143, 1725-1734. (Pubitemid 29006515)
54. Itoh, M., Nagafuchi, A., Moroi, S. and Tsukita, S. (1997). Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments. J. Cell Biol. 138, 181-192. (Pubitemid 27337462)
55. Jørgensen, N., Asklund, C., Carlsen, E. and Skakkebaek, N. E. (2006). Coordinated European investigations of semen quality: results from studies of Scandinavian young men is a matter of concern. Int. J. Androl. 29, 54-61.
56. Juneja, S. C. (2003). mRNA expression pattern of multiple members of connexin gene family in normal and abnormal fetal gonads in mouse. Indian J. Physiol. Pharmacol. 47, 147-156.
57. Juneja, S. C., Barr, K. J., Enders, G. C. and Kidder, G. M. (1999). Defects in the germ line and gonads of mice lacking connexin43. Biol. Reprod. 60, 1263-1270. (Pubitemid 29196784)
58. Kameritsch, P., Pogoda, K. and Pohl, U. (2011). Channel-independent influence of connexin 43 on cell migration. Biochim. Biophys. Acta doi:10.1016/j.bbamem.2011.11.016.
59. Kanetsky, P. A., Mitra, N., Vardhanabhuti, S., Vaughn, D. J., Li, M., Ciosek, S. L., Letrero, R., D'Andrea, K., Vaddi, M., Doody, D. R. et al. (2011). A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. Hum. Mol. Genet. 20, 3109-3117.
60. Kardami, E., Dang, X., Iacobas, D. A., Nickel, B. E., Jeyaraman, M., Srisakuldee, W., Makazan, J., Tanguy, S. and Spray, D. C. (2007). The role of connexins in controlling cell growth and gene expression. Prog. Biophys. Mol. Biol. 94, 245-264. (Pubitemid 46782981)
61. Kawamata, M., Inoue, H. and Nishimori, K. (2007). Male-specific function of Dmrt7 by sexually dimorphic translation in mouse testis. Sex. Dev. 1, 297-304. (Pubitemid 350136535)
62. Kerr, C. L. and Cheng, L. (2010). The dazzle in germ cell differentiation. J. Mol. Cell. Biol. 2, 26-29.
63. Kim, S., Kettlewell, J. R., Anderson, R. C., Bardwell, V. J. and Zarkower, D. (2003). Sexually dimorphic expression of multiple doublesex-related genes in the embryonic mouse gonad. Gene. Expr. Patterns 3, 77-82. (Pubitemid 36356046)
64. Kim, S., Namekawa, S. H., Niswander, L. M., Ward, J. O., Lee, J. T., Bardwell, V. J. and Zarkower, D. (2007). A mammal-specific Doublesex homolog associates with male sex chromatin and is required for male meiosis. PLoS Genet. 3, e62.
65. Kim, K. Y., Kim, B. J. and Yi, G. S. (2004). Reuse of imputed data in microarray analysis increases imputation efficiency. BMC Bioinformatics 5, 160.
66. Kliesch, S., Behre, H. M., Hertle, L. and Bergmann, M. (1998). Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes. J. Urol. 160, 1894-1898. (Pubitemid 128746782)
67. Kuramochi-Miyagawa, S., Kimura, T., Ijiri, T. W., Isobe, T., Asada, N., Fujita, Y., Ikawa, M., Iwai, N., Okabe, M., Deng, W. et al. (2004). Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development 131, 839-849. (Pubitemid 38263199)
68. Lee, J. H., Engel, W. and Nayernia, K. (2006a). Stem cell protein piwil2 modulates expression of murine spermatogonial stem cell expressed genes. Mol. Reprod. Dev. 73, 173-179. (Pubitemid 43054341)
69. Lee, N. P., Leung, K. W., Wo, J. Y., Tam, P. C., Yeung, W. S. and Luk, J. M. (2006b). Blockage of testicular connexins induced apoptosis in rat seminiferous epithelium. Apoptosis 11, 1215-1229. (Pubitemid 44035969)
70. Li, B., Nair, M., Mackay, D. R., Bilanchone, V., Hu, M., Fallahi, M., Song, H., Dai, Q., Cohen, P. E. and Dai, X. (2005). Ovol1 regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression. Development 132, 1463-1473. (Pubitemid 40528803)
71. Lin, Y. M., Chen, C. W., Sun, H. S., Tsai, S. J., Hsu, C. C., Teng, Y. N., Lin, J. S. and Kuo, P. L. (2001). Expression patterns and transcript concentrations of the autosomal DAZL gene in testes of azoospermic men. Mol. Hum. Reprod. 7, 1015-1022. (Pubitemid 33040964)
72. Lin, Y. N., Roy, A., Yan, W., Burns, K. H. and Matzuk, M. M. (2007). Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol. Cell. Biol. 27, 6794-6805. (Pubitemid 47483630)
73. Looijenga, L. H., Hersmus, R., Gillis, A. J., Pfundt, R., Stoop, H. J., van Gurp, R. J., Veltman, J., Beverloo, H. B., van Drunen, E., van Kessel, A. G. et al. (2006). Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene. Cancer Res. 66, 290-302. (Pubitemid 43166035)
74. Maratou, K., Forster, T., Costa, Y., Taggart, M., Speed, R. M., Ireland, J., Teague, P., Roy, D. and Cooke, H. J. (2004). Expression profiling of the developing testis in wild-type and Dazl knockout mice. Mol. Reprod. Dev. 67, 26-54. (Pubitemid 37467335)
75. Møller, H. and Skakkebaek, N. E. (1999). Risk of testicular cancer in subfertile men: case-control study. BMJ 318, 559-562. (Pubitemid 29188952)
76. Mruk, D. D. and Cheng, C. Y. (2004). Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr. Rev. 25, 747-806. (Pubitemid 39362296)
77. Murphy, M. W., Zarkower, D. and Bardwell, V. J. (2007). Vertebrate DM domain proteins bind similar DNA sequences and can heterodimerize on DNA. BMC Mol. Biol. 8, 58.
78. Nagano, T. and Suzuki, F. (1976). Freeze-fracture observations on the intercellular junctions of Sertoli cells and of Leydig cells in the human testis. Cell Tissue Res. 166, 37-48.
79. Orth, J. M. (1982). Proliferation of Sertoli cells in fetal and postnatal rats: a quantitative autoradiographic study. Anat. Rec. 203, 485-492.
80. Pangas, S. A., Choi, Y., Ballow, D. J., Zhao, Y., Westphal, H., Matzuk, M. M. and Rajkovic, A. (2006). Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc. Natl. Acad. Sci. USA 103, 8090-8095. (Pubitemid 43801057)
81. Pelletier, R. M. (1995). 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. 16, 400-409.
82. Pérez-Armendariz, E. M., Romano, M. C., Luna, J., Miranda, C., Bennett, M. V. and Moreno, A. P. (1994). Characterization of gap junctions between pairs of Leydig cells from mouse testis. Am. J. Physiol. 267, C570-C580.
83. Pointis, G. and Segretain, D. (2005). Role of connexin-based gap junction channels in testis. Trends Endocrinol. Metab. 16, 300-306. (Pubitemid 41206636)
84. Pointis, G., Fiorini, C., Defamie, N. and Segretain, D. (2005). Gap junctional communication in the male reproductive system. Biochim. Biophys. Acta 1719, 102-116. (Pubitemid 41785639)
85. Pointis, G., Gilleron, J., Carette, D. and Segretain, D. (2010). Physiological and physiopathological aspects of connexins and communicating gap junctions in spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1607-1620.
86. Pointis, G., Gilleron, J., Carette, D. and Segretain, D. (2011). Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility. Spermatogenesis 1, 303-317.
87. Povey, A. C. and Stocks, S. J. (2010). Epidemiology and trends in male subfertility. Hum. Fertil. (Camb.) 13, 182-188.
88. Raverot, G., Weiss, J., Park, S. Y., Hurley, L. and Jameson, J. L. (2005). Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Dev. Biol. 283, 215-225. (Pubitemid 40828853)
89. Raymond, C. S., Murphy, M. W., O'Sullivan, M. G., Bardwell, V. J. and Zarkower, D. (2001). Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev. 14, 2587-2595.
90. Reaume, A. G., de Sousa, P. A., Kulkarni, S., Langille, B. L., Zhu, D., Davies, T. C., Juneja, S. C., Kidder, G. M. and Rossant, J. (1995). Cardiac malformation in neonatal mice lacking connexin43. Science 267, 1831-1834.
91. Reber, M. and Cereghini, S. (2001). Variant hepatocyte nuclear factor 1 expression in the mouse genital tract. Mech. Dev. 100, 75-78.
92. Risley, M. S., Tan, I. P., Roy, C. and Saez, J. C. (1992). Cell-, age- and stage-dependent distribution of connexin43 gap junctions in testes. J. Cell Sci. 103, 81-96.
93. Rodriguez, I., Ody, C., Araki, K., Garcia, I. and Vassalli, P. (1997). An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis. EMBO J. 16, 2262-2270. (Pubitemid 27260376)
94. Rogatsch, H., Jezek, D., Hittmair, A., Mikuz, G. and Feichtinger, H. (1996). Expression of vimentin, cytokeratin, and desmin in Sertoli cells of human fetal, cryptorchid, and tumour-adjacent testicular tissue. Virchows Arch. 427, 497-502. (Pubitemid 126828181)
95. Roger, C., Mograbi, B., Chevallier, D., Michiels, J. F., Tanaka, H., Segretain, D., Pointis, G. and Fenichel, P. (2004). Disrupted traffic of connexin 43 in human testicular seminoma cells: overexpression of Cx43 induces membrane location and cell proliferation decrease. J. Pathol. 202, 241-246. (Pubitemid 38208662)
96. Roscoe, W. A., Barr, K. J., Mhawi, A. A., Pomerantz, D. K. and Kidder, G. M. (2001). Failure of spermatogenesis in mice lacking connexin43. Biol. Reprod. 65, 829-838. (Pubitemid 32777370)
97. Ruggiu, M., Speed, R., Taggart, M., McKay, S. J., Kilanowski, F., Saunders, P., Dorin, J. and Cooke, H. J. (1997). The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389, 73-77. (Pubitemid 27387693)
98. Saitou, M., Furuse, M., Sasaki, H., Schulzke, J. D., Fromm, M., Takano, H., Noda, T. and Tsukita, S. (2000). Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol. Biol. Cell 11, 4131-4142.
99. Sapiro, R., Kostetskii, I., Olds-Clarke, P., Gerton, G. L., Radice, G. L. and Strauss, I. J. (2002). Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6. Mol. Cell. Biol. 22, 6298-6305. (Pubitemid 34857847)
100. Saunders, P. T., Turner, J. M., Ruggiu, M., Taggart, M., Burgoyne, P. S., Elliott, D. and Cooke, H. J. (2003). Absence of mDazl produces a final block on germ cell development at meiosis. Reproduction 126, 589-597. (Pubitemid 37540618)
101. Schleiermacher, E. (1980). Ultrastructural changes of the intercellular relationship in impaired human spermatogenesis. Hum. Genet. 54, 391-404.
102. Sharpe, R. M. (2010). Environmental/lifestyle effects on spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1697-1712.
103. Sharpe, R. M., McKinnell, C., Kivlin, C. and Fisher, J. S. (2003). Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125, 769-784. (Pubitemid 36722545)
104. Skakkebaek, N. E., Rajpert-De Meyts, E. and Main, K. M. (2001). Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 16, 972-978. (Pubitemid 32451837)
105. Sohl, G. and Willecke, K. (2004). Gap junctions and the connexin protein family. Cardiovasc. Res. 62, 228-232. (Pubitemid 38496536)
106. Spray, D. C., Ye, Z. C. and Ransom, B. R. (2006). Functional connexin "hemichannels": a critical appraisal. Glia 54, 758-773. (Pubitemid 44629638)
107. Sridharan, S., Simon, L., Meling, D. D., Cyr, D. G., Gutstein, D. E., Fishman, G. I., Guillou, F. and Cooke, P. S. (2007a). Proliferation of adult Sertoli cells following conditional knockout of the Gap junctional protein GJA1 (connexin 43) in mice. Biol. Reprod. 76, 804-812. (Pubitemid 46651221)
108. Sridharan, S., Brehm, R., Bergmann, M. and Cooke, P. S. (2007b). Role of connexin 43 in Sertoli cells of testis. Ann. N. Y. Acad. Sci. 1120, 131-143.
109. Steger, K., Rey, R., Kliesch, S., Louis, F., Schleicher, G. and Bergmann, M. (1996). Immunohistochemical detection of immature Sertoli cell markers in testicular tissue of infertile adult men: a preliminary study. Int. J. Androl. 19, 122-128. (Pubitemid 26158693)
110. Steger, K., Aleithe, I., Behre, H. and Bergmann, M. (1998). The proliferation of spermatogonia in normal and pathological human seminiferous epithelium: an immunohistochemical study using monoclonal antibodies against Ki-67 protein and proliferating cell nuclear antigen. Mol. Hum. Reprod. 4, 227-233. (Pubitemid 28172588)
111. Steger, K., Tetens, F. and Bergmann, M. (1999). Expression of connexin 43 in human testis. Histochem. Cell Biol. 112, 215-220. (Pubitemid 29475991)
112. Steiner, M., Weipoltshammer, K., Viehberger, G., Meixner, E. M., Lunglmayr, G. and Schöfer, C. (2011). Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor. Histochem. Cell Biol. 135, 73-81.
113. Stout, C., Goodenough, D. A. and Paul, D. L. (2004). Connexins: functions without junctions. Curr. Opin. Cell Biol. 16, 507-512. (Pubitemid 39201234)
114. Tanmahasamut, P. and Sidell, N. (2005). Up-regulation of gap junctional intercellular communication and connexin43 expression by retinoic acid in human endometrial stromal cells. J. Clin. Endocrinol. Metab. 90, 4151-4156. (Pubitemid 41058190)
115. Tsai-Morris, C. H., Sheng, Y., Lee, E., Lei, K. J. and Dufau, M. L. (2004). Gonadotropinregulated testicular RNA helicase (GRTH Ddx25) is essential for spermatid development and completion of spermatogenesis. Proc. Natl. Acad. Sci. USA 101, 6373-6378. (Pubitemid 38585981)
116. Vine, A. L. and Bertram, J. S. (2005). Upregulation of connexin 43 by retinoids but not by non-provitamin A carotenoids requires RARs. Nutr. Cancer 52, 105-113. (Pubitemid 41232655)
117. Wang, P. J., McCarreay, J. R., Yang, F. and Page, D. C. (2001). An abundance of X-linked genes expressed in spermatogonia. Nat. Genet. 27, 422-426. (Pubitemid 32268424)
118. Weider, K., Bergmann, M. and Brehm, R. (2011a). Connexin 43, its regulatory role in testicular junction dynamics and spermatogenesis. Histol. Histopathol. 26, 1343-1352.
119. Weider, K., Bergmann, M., Giese, S., Guillou, F., Failing, K. and Brehm, R. (2011b). Altered differentiation and clustering of Sertoli cells in transgenic mice showing a Sertoli cell specific knockout of the connexin 43 gene. Differentiation 82, 38-49.
120. WHO (1987). Towards more objectivity in diagnosis and management of male fertility. Int. J. Androl. 7, 1-53.
121. Yang, F., De La Fuente, R., Leu, N. A., Baumann, C., McLaughlin, K. J. and Wang, P. J. (2006). Mouse SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis. J. Cell Biol. 173, 497-507. (Pubitemid 43765197)
122. Yang, F., Gell, K., van der Heijden, G. W., Eckardt, S., Leu, A. N., Page, D. C., Benavente, R., Her, C., Höög, C., McLaughlin, K. J. et al. (2008). Meiotic failure in male mice lacking an X-linked factor. Genes Dev. 22, 682-691. (Pubitemid 351342439)
123. Zhou, Q., Nie, R., Li, Y., Friel, P., Mitchellm, D., Hess, R. A., Small, C. and Griswold, M. D. (2008). Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells induced by retinoic acid: an in vivo study in vitamin A-sufficient postnatal murine testes. Biol. Reprod. 79, 35-42. (Pubitemid 351931040)