Connexin 43 a potential regulator of cell proliferation and apoptosis within the seminiferous epithelium.
The gap junction proteins, connexins (Cx), are present in the testis and among them Cx43 play an essential role in spermatogenesis. By using an in vitro proliferation model of germ cells and Sertoli cells, we tempted here to clarify the role of Cx43 in the control of Sertoli and germ cell proliferation and apoptosis. Cx43 was detected in purified preparations of Sertoli cells and spermatogonia and immunolocalized in both cell types identified by vimentin and c-kit, respectively. Inhibition of gap junction coupling by the gap junction inhibitor alpha-GA significantly enhanced BrdU incorporation in Sertoli cells and reduced the number of activated caspase-3 positive germ cells. Similarly, inhibitory Cx43 and pan-Cx mimetic inhibitory peptides increased proliferation of Sertoli cells and stimulated survival of germ cells. Cx32 mimetic inhibitory peptide also stimulated Sertoli cell proliferation without altering germ cell proliferation and apoptosis. The present results reveal that Cx43 gap junctions between Sertoli cells participate in the control of Sertoli cell proliferation and that Cx43 gap junctions between Sertoli cells and spermatogonia are indirectly involved in germ cell number increase by controlling germ cell survival rather than germ cell proliferation.
Gilleron
Jérome
J
INSERM U 895, Team 5 Physiopathology of germ cell control: genomic and non genomic mechanisms C3M, 151 route Saint-Antoine de Ginestière, BP 2 3194, 06204 Nice cedex 3, France.
Carette
Diane
D
Durand
Philippe
P
Pointis
Georges
G
Segretain
Dominique
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000502:physiology; D002470:Cell Survival; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D018031:Connexin 43; D014746:Vimentin