Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Department of Urology, Chonbuk National University Medical School (JKP), Jeonju, Republic of Korea.
Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea; Department of Urology, Chonbuk National University Medical School (JKP), Jeonju, Republic of Korea.
J Urol. 2016 Oct;196(4):1303-12. doi: 10.1016/j.juro.2016.05.004. Epub 2016 May 7.
To elucidate the changes that occur in the blood-testis barrier during varicocele we examined changes in Cldn11 (claudin-11), an element of the blood-testis barrier, as well as steroidogenesis and proinflammatory cytokines in a model of varicocele rat testes.
Male rats with experimentally induced varicocele were sacrificed 4 weeks after operation. Testicular histology and blood testosterone concentrations were examined. The expression of tight junctions, steroidogenic enzymes, apoptosis and immune cell markers, and proinflammatory cytokines in the testes were evaluated by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry.
Weight and Johnsen scores of varicocele testes were lower than those of normal testes. mRNA expression of Bad and Bax increased whereas Bcl-xl and Bcl2 mRNA decreased in varicocele testes compared to controls. Although blood testosterone did not change, Leydig cell 3βHsd immunoreactivity, testicular 3βHsd6 and 17βHsd3 mRNA were significantly decreased in varicocele testes. Cldn11 mRNA and protein levels in varicocele testes were higher than in normal testes together with altered expression of Ocln, Zo1 and N-cadherin mRNA. Cldn11 immunoreactivity appeared as wavy strands at the periphery of the seminiferous epithelium in normal testes but was frequently found in the Sertoli cell cytoplasm in varicocele testes. In varicocele testes Tnfα, Il1α, Il6, Cd45, Cd3g and Cd3d mRNA was increased.
An increase in proinflammatory cytokines might be responsible for deregulation of Cldn11 in the Sertoli cells in varicocele testes, leading to alterations in the permeability of the blood-testis barrier and immunological barriers to normal spermatogenesis.
为了阐明精索静脉曲张时血睾屏障的变化,我们研究了精索静脉曲张大鼠睾丸模型中血睾屏障的组成部分 Claudin-11(紧密连接蛋白 11)以及类固醇生成和促炎细胞因子的变化。
雄性大鼠精索静脉曲张造模 4 周后处死,检测睾丸组织学和血睾酮浓度。采用逆转录聚合酶链反应、Western blot 和免疫组化法检测睾丸中紧密连接、类固醇生成酶、凋亡和免疫细胞标志物以及促炎细胞因子的表达。
精索静脉曲张睾丸的重量和 Johnsen 评分低于正常睾丸。与对照组相比,精索静脉曲张睾丸中 Bad 和 Bax 的 mRNA 表达增加,而 Bcl-xl 和 Bcl2 的 mRNA 表达减少。虽然血睾酮没有变化,但 3βHsd 免疫反应性、睾丸 3βHsd6 和 17βHsd3mRNA 明显降低。与正常睾丸相比,精索静脉曲张睾丸的 Cldn11mRNA 和蛋白水平升高,Ocln、Zo1 和 N-cadherinmRNA 的表达也发生改变。正常睾丸生精上皮边缘的 Claudin11 免疫反应呈波浪状,但精索静脉曲张睾丸的 Sertoli 细胞质中经常发现 Claudin11 免疫反应。在精索静脉曲张睾丸中,Tnfα、Il1α、Il6、Cd45、Cd3g 和 Cd3d 的 mRNA 表达增加。
促炎细胞因子的增加可能导致精索静脉曲张睾丸中 Sertoli 细胞 Claudin11 的失调,导致血睾屏障和免疫屏障正常精子发生的通透性改变。