Stammler Angelika, Lüftner Benjamin Udo, Kliesch Sabine, Weidner Wolfgang, Bergmann Martin, Middendorff Ralf, Konrad Lutz
Justus-Liebig-University Giessen, Institute of Anatomy and Cell Biology, Aulweg 123, D-35392, Giessen, Germany.
Justus-Liebig-University Giessen, Department of Obstetrics and Gynecology, Feulgenstraße 12, D-35392, Giessen, Germany.
PLoS One. 2016 Aug 3;11(8):e0160349. doi: 10.1371/journal.pone.0160349. eCollection 2016.
In this study we tested expression of tight junction proteins in human, mouse and rat and analyzed the localization of claudin-11 in testis of patients with normal and impaired spermatogenesis. Recent concepts generated in mice suggest that the stage-specifically expressed claudin-3 acts as a basal barrier, sealing the seminiferous epithelium during migration of spermatocytes. Corresponding mechanisms have never been demonstrated in humans. Testicular biopsies (n = 103) from five distinct groups were analyzed: normal spermatogenesis (NSP, n = 28), hypospermatogenesis (Hyp, n = 24), maturation arrest at the level of primary spermatocytes (MA, n = 24), Sertoli cell only syndrome (SCO, n = 19), and spermatogonial arrest (SGA, n = 8). Protein expression of claudin-3, -11 and occludin was analyzed. Human, mice and rat testis robustly express claudin-11 protein. Occludin was detected in mouse and rat and claudin-3 was found only in mice. Thus, we selected claudin-11 for further analysis of localization. In NSP, claudin-11 is located at Sertoli-Sertoli junctions and in Sertoli cell contacts towards spermatogonia. Typically, claudin-11 patches do not reach the basal membrane, unless flanked by the Sertoli cell body or patches between two Sertoli cell bodies. The amount of basal claudin-11 patches was found to be increased in impaired spermatogenesis. Only claudin-11 is expressed in all three species examined. The claudin-11 pattern is robust in man with impaired spermatogenesis, but the proportion of localization is altered in SCO and MA. We conclude that claudin-11 might represent the essential component of the BTB in human.
在本研究中,我们检测了紧密连接蛋白在人、小鼠和大鼠中的表达,并分析了闭合蛋白-11在精子发生正常和受损患者睾丸中的定位。在小鼠中产生的最新概念表明,阶段特异性表达的闭合蛋白-3作为一种基底屏障,在精母细胞迁移过程中封闭生精上皮。相应的机制在人类中从未得到证实。分析了来自五个不同组的睾丸活检样本(n = 103):正常精子发生(NSP,n = 28)、精子发生低下(Hyp,n = 24)、初级精母细胞水平的成熟停滞(MA,n = 24)、唯支持细胞综合征(SCO,n = 19)和精原细胞停滞(SGA,n = 8)。分析了闭合蛋白-3、-11和闭合蛋白的蛋白表达。人、小鼠和大鼠睾丸均强烈表达闭合蛋白-11蛋白。在小鼠和大鼠中检测到闭合蛋白,而闭合蛋白-3仅在小鼠中发现。因此,我们选择闭合蛋白-11进行进一步的定位分析。在NSP中,闭合蛋白-11位于支持细胞-支持细胞连接以及支持细胞与生精细胞的接触部位。通常,闭合蛋白-11斑块不会到达基底膜,除非两侧有支持细胞体或两个支持细胞体之间的斑块。发现在精子发生受损时基底闭合蛋白-11斑块的数量增加。在所检测的所有三个物种中仅表达闭合蛋白-11。在精子发生受损的男性中,闭合蛋白-11模式很明显,但在SCO和MA中定位比例发生了改变。我们得出结论,闭合蛋白-11可能是人类血睾屏障的重要组成部分。