SOX8 Regulates Permeability of the Blood-Testes Barrier That Affects Adult Male Fertility in the Mouse
SOX8 Regulates Permeability of the Blood-Testes Barrier That Affects Adult Male Fertility in the Mouse
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DOI：
10.1095/biolreprod.112.107284
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发表时间：
2013-05-01
影响因子：
3.6
通讯作者：
Archer, Trevor K.
中科院分区：
文献类型：
--
作者：
Singh, Ajeet Pratap;Cummings, Connie A.;Archer, Trevor K.
支持细胞在精子发生过程中为生殖细胞提供营养和生理支持。Sox 8编码与Sox 9和Sox 10密切相关的转录因子的高迁移率组的成员。支持细胞表达SOX 8蛋白，其消除导致年龄依赖性精子发生失调，导致成年男性不育。在Sox 8（-/-）睾丸中具有改变的表达的封闭蛋白基因中，是调节和维持血-睾丸屏障（BTB）所需的封闭蛋白-3。由于BTB在限制生精小管腔室中的小分子方面至关重要，因此本研究的目的是分析Sox 8（-/-）成人睾丸中紧密连接蛋白（claudin-3、claudin-11和occludin）的水平和BTB渗透性。还评价了α-微管蛋白和微管组织的乙酰化水平，因为微管在维持生精上皮的微环境中至关重要。Western blot分析显示，在Sox 8（-/-）睾丸中，claudin-3蛋白减少。染色质免疫沉淀证实，SOX 8结合在claudin-3的启动子区。Claudin-3定位于野生型睾丸的支持细胞紧密连接，并在Sox 8（-/-）睾丸中显著降低。生物素示踪剂的使用显示Sox 8（-/-）成人睾丸中BTB渗透性增加。电子显微镜分析表明，微管结构不稳定的Sox 8（-/-）睾丸。这些结果表明，Sox 8是必不可少的支持细胞的生殖细胞分化，部分通过控制生精上皮的微环境。
Sertoli cells provide nutritional and physical support to germ cells during spermatogenesis. Sox8 encodes a member of the high mobility group of transcription factors closely related to Sox9 and Sox10. Sertoli cells express SOX8 protein, and its elimination results in an age-dependent dysregulation of spermatogenesis, causing adult male infertility. Among the claudin genes with altered expression in the Sox8(-/-) testes, was claudin-3, which is required for the regulation and maintenance of the blood-testes barrier (BTB). Because the BTB is critical in restricting small molecules in the luminal compartment of the seminiferous tubules, the aim of this study was to analyze the level of tight junction proteins (claudin-3, claudin-11, and occludin) and BTB permeability in Sox8(-/-) adult testes. The acetylation level of alpha-tubulin and microtubule organization was also evaluated because microtubules are critical in maintaining the microenvironment of the seminiferous epithelium. Western blot analysis shows that claudin-3 protein is decreased in Sox8(-/-) testes. Chromatin immunoprecipitation confirmed that SOX8 binds at the promoter region of claudin-3. Claudin-3 was localized to the Sertoli cell tight junctions of wildtype testes and significantly decreased in the Sox8(-/-) testes. The use of biotin tracers showed increased BTB permeability in the Sox8(-/-) adult testes. Electron microscopy analysis showed that microtubule structures were destabilized in the Sox8(-/-) testes. These results suggest that Sox8 is essential in Sertoli cells for germ cell differentiation, partly by controlling the microenvironment of the seminiferous epithelium.