Fiorini Céline, Tilloy-Ellul Anne, Chevalier Stephan, Charuel Claude, Pointis Georges
INSERM EMI 00-09, IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 02, France.
Reprod Toxicol. 2004 May;18(3):413-21. doi: 10.1016/j.reprotox.2004.01.002.
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.
在睾丸中，支持细胞建立细胞间连接，这对精子发生至关重要。SerW3支持细胞系表现出一些天然支持细胞的特征。蛋白质免疫印迹和免疫荧光分析表明，SerW3支持细胞表达紧密连接（闭合蛋白和闭合小带蛋白-1）、锚定连接（N-钙黏蛋白）和缝隙连接（连接蛋白43）的典型成分。睾丸毒物（滴滴涕、五氯苯酚、狄氏剂、二硝基苯、氯化镉、顺铂、棉酚、双酚A和叔辛基苯酚）通过减少这些膜蛋白的量或诱导其异常的细胞内定位来影响细胞间连接。磷酸二酯酶抑制剂（异丁基甲基黄嘌呤、咯利普兰、扎普司特、扎达维林）不会改变连接复合体成分的水平，但会导致这些蛋白迅速且可逆地重新分布到细胞质区室。本研究表明，闭合蛋白、闭合小带蛋白-1、N-钙黏蛋白，特别是连接蛋白43可能是睾丸毒物的早期作用靶点。因此，SerW3细胞系似乎是一种有用的体外模型，可用于评估具有潜在抗生殖作用的分子。
