血-睾丸屏障是哺乳动物睾丸内的特殊特征,位于生精小管基底膜附近。该屏障用于将生精上皮分为不同的基底和腔内(顶端)隔室。BTB对外来颗粒的选择性使其成为病毒的避风港,HIV对睾丸的高亲和力可能导致病毒的垂直传播。在本研究中,静脉注射重组HIV1-Nef(rNef)蛋白以检查rNef对BTB的影响。SD雄性大鼠通过尾静脉接受250µg和500µgrNef以及1ml内的2%Evans蓝染料。灌注1小时后,处死动物用于分析。染料迁移测定和ELISA证实了血睾丸屏障(BTB)的显着损害和睾丸组织中rNef的表现,分别。此外,紧密连接蛋白表达的下降,包括ZO1和Occludin,在rNef诱导的BTB破坏期间观察到。总的来说,我们的研究结果表明,rNef通过各种信号传导事件诱导BTB破坏.在生精上皮的外质特化部位,发现钙黏着蛋白的定位被破坏,使睾丸成为脆弱的部位.总之,rNef扰乱了大鼠模型中血液-睾丸屏障的完整性;因此,它也可以作为研究血睾丸屏障动力学的合适模型。
建立啮齿动物模型以研究血液睾丸屏障(BTB)的完整性。HIV1的重组Nef(rNef)可以突破BTB最艰难的生理屏障。通过BTB动态的“脱离”和“参与”机制,rNef中断了BTB的完整性。BTB的主要组成蛋白,包括Occludin和ZO-1被发现被rNef高度破坏;并且似乎是受损BTB的关键异常。rNef还使大鼠睾丸中N&E钙粘蛋白的定位脱位;这会影响BTB的基于钙粘蛋白的上皮粘附系统,并最终导致破裂。
The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.
Established a rodent model to study the integrity of the blood testis barrier (BTB).Recombinant Nef (rNef) of HIV1 can breach the toughest physiological barrier of BTB.Integrity of BTB gets interrupted by rNef through the ‘disengagement’ and ‘engagement’ mechanisms of BTB dynamics.Major constituent proteins of BTB, including Occludin and ZO-1 were found to be highly disrupted by rNef; and seem to be the key aberrant for the compromised BTB.rNef also dislocated the localization of N & E cadherins in the rat testes; which would have affected the cadherin-based epithelial adhesion system of BTB and finally caused the breach.