Scrotal heat stress causes a transient alteration in tight junctions and induction of TGF-β expression

作者：Huan Cai, Yu Ren, X.-X. Li, Junling Yang, C.-P. Zhang, Miao-gen Chen, Chunhai Fan, Xinning Hu, Z.-Y. Hu, Fei Gao, Yuhan Liu · 发表于：International Journal of Andrology · 年份：2010 · DOI：10.1111/j.1365-2605.2010.01089.x · 被引用次数：90 · 研究领域：Sperm and Testicular Function、Prostate Cancer Diagnosis and Treatment、Barrier Structure and Function Studies

Specialized junctions, which occur at sites of Sertoli-Sertoli and Sertoli-germ cell contact of seminiferous epithelium, play pivotal roles in spermatogenesis. Slight increase in scrotal temperature can induce oligospermia or azoospermia via increasing germ cell apoptosis. In this study, we demonstrated that the expression of tight junction (TJ) components, such as occludin, claudin-3 and zonula occludens-1 (ZO-1), was reduced 24-48h after a single mild scrotal heat exposure (43°C for 30min), whereas mRNA levels of claudin-11 were increased. Moreover, the protein localization of occludin and ZO-1 was lost from the blood-testis barrier (BTB) site, whereas claudin-11 immunostaining became diffuse and cytoplasmic 2days following heat exposure. Electron microscopic analysis showed that 2days after the heat treatment, the intercellular space between the two adjacent Sertoli cells was expanded, coupled with defragmentation of actin bundles and the endoplasmic reticulum. In addition, the TJ permeability increased significantly 2days after the heat exposure and recovered approximately 10days later. Heat-induced reversible BTB disruption was associated with a transient induction of transforming growth factor (TGF)-β2, -3 and p38 mitogen-activated protein kinase activation. However, the TGF-β antagonist only partially prevented the heat-induced BTB disruption. In conclusion, the expression of TJ-associated molecules and BTB were reversibly perturbed after mild testicular hyperthermia, ...