Sertoli cell junctional proteins as early targets for different classes of reproductive toxicants.
In the testis, Sertoli cells establish intercellular junctions that are essential for spermatogenesis. The SerW3 Sertoli cell line displays some features of native Sertoli cells. Western blot and immunofluorescence analyses showed that SerW3 Sertoli cells expressed typical components of tight (occludin and zonula occludens-1), anchoring (N-cadherin) and gap (connexin 43) junctions. Testicular toxicants (DDT, pentachlorophenol, dieldrin, dinitrobenzene, cadmium chloride, cisplatin, gossypol, bisphenol A and tert-octylphenol) affected intercellular junctions by either reducing the amount or inducing aberrant intracellular localization of these membranous proteins. Phosphodiesterase inhibitors (isobutyl methylxantine, rolipram, zaprinast, zardaverine) did not alter junctional-complex component levels but caused a rapid and reversible redistribution of these proteins to the cytoplasmic compartment. The present study showed that occludin, ZO-1, N-cadherin and specifically Cx43 could be early targets for testicular toxicants. The SerW3 cell line therefore appears as a useful in vitro model to evaluate molecules with potential anti-reproductive effects.
Fiorini
Céline
C
INSERM EMI 00-09, IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 02, France.
Tilloy-Ellul
Anne
A
Chevalier
Stephan
S
Charuel
Claude
C
Pointis
Georges
G
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000187:drug effects* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004785:Environmental Pollutants / Q000633:toxicity*; D045166:Estradiol Congeners / Q000633:toxicity; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008670:Metals / Q000633:toxicity; D062793:Occludin; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism*; D013723:Teratogens / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D015820:Cadherins; D018031:Connexin 43; D017630:Connexins; D004785:Environmental Pollutants; D045166:Estradiol Congeners; D008565:Membrane Proteins; D008670:Metals; D062793:Occludin; C568987:Ocln protein, rat; D010726:Phosphodiesterase Inhibitors; D013723:Teratogens; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue