Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility.
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, beta-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 beta-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.
Carette
Diane
D
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, France.
Weider
Karola
K
Gilleron
Jérome
J
Giese
Sarah
S
Dompierre
Jim
J
Bergmann
Martin
M
Brehm
Ralph
R
Denizot
Jean-Pierre
JP
Segretain
Dominique
D
Pointis
Georges
G
D000818:Animals; D015820:Cadherins / Q000032:analysis; D002460:Cell Line; D018031:Connexin 43 / Q000502:physiology*; D005298:Fertility; D017629:Gap Junctions / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D062793:Occludin; D010750:Phosphoproteins / Q000032:analysis; D012670:Seminiferous Epithelium / Q000502:physiology*; D012708:Sertoli Cells / Q000502:physiology; D013091:Spermatogenesis; D062826:Zonula Occludens-1 Protein
D015820:Cadherins; C489083:Cdh2 protein, mouse; D018031:Connexin 43; C543076:GJA1 protein, mouse; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein