Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility |
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| Authors: | Diane Carette Karola Weider Sarah Giese Martin Bergmann Jean-Pierre Denizot Georges Pointis |
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| Institution: | a INSERM U 895, Team 5 «Physiopathology of germ cell control: genomic and non genomic mechanisms» Centre Méditerranéen de Médecine Moléculaire, Nice, F-06204 Cedex 3, Franceb University Nice Sophia Antipolis, 151 route Saint Antoine de Ginestière BP 2 3194 06204 Nice Cedex 3, Francec Justus-Liebig-University, Department of Veterinary Anatomy, Histology and Embryology, Frankfurter Strasse 98, 35392 Giessen, Germanyd Zerial Laboratory, Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01309, Dresden, Germanye UMR S775, University Paris Descarte, 45 rue des Saints Pères, 75006, Paris, Francef Department of Anatomy, University of Veterinary Medicine, Bischofsholer Damm 15, 30173 Hannover, Germanyg CNRS, Unité de Neurosciences, Information et Complexité, 91198 Gif-sur-Yvette, France |
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| Abstract: | In different epithelia, cell membranes contacting one another form intercellular junctional complexes including tight, adherens and gap junctions, which could mutually influence the expression of each other. We have here investigated the role of Cx43 in the control of adherens and tight junction proteins (N-cadherin, β-catenin, occludin and ZO-1) by using conditional Sertoli cell knockout Cx43 (SCCx43KO−/−) transgenic mice and specific anti-Cx43 siRNA. Gap junction coupling and Cx43 levels were reduced in SCCx43KO−/− as compared to Wild-type testes. Ultrastructural analysis revealed disappearance of gap junctions, the presence of tight and adherens junctions and persistent integrity of the blood-testis barrier in SCCx43KO−/− testis. Occludin, N-cadherin and β-catenin levels were enhanced in SCCx43KO−/− mice as compared to Wild-type animals whereas ZO-1 levels were reduced. Cx43 siRNA blocked gap junction functionality in Sertoli cells and altered tight and adherens protein levels. The Cx43 control of tight and adherens junctions appeared channel-dependent since gap junction blockers (glycyrrhetinic acid and oleamide) led to similar results. These data suggest that the control of spermatogenesis by Cx43 may be mediated through Sertoli cell Cx43 channels, which are required, not only in cell/cell communication between Sertoli and germ cells, but also in the regulation of other junctional proteins essential for the blood-testis barrier. |
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| Keywords: | Cx43 Gap junction Sertoli cell knockout Cx43 siRNA Tight junction Adherens junction Fertility |
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