Cholesterol-enriched diet disrupts the blood-testis barrier in rabbits
Cholesterol-enriched diet disrupts the blood-testis barrier in rabbits
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DOI：
10.1152/ajpendo.00416.2014
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发表时间：
2014-12-15
影响因子：
5.1
通讯作者：
Chen, Xuesong
中科院分区：
文献类型：
--
作者：
Morgan, Daniel H.;Ghribi, Othman;Chen, Xuesong
在美国，大约15%的异性恋夫妇患有不育症;男性不育症占所有不育症病例的50%，大约50%的男性不育症是特发性的。血浆胆固醇水平升高对精子发生和男性生育力产生负面影响，但机制尚不清楚。显然，精子发生发生在受血睾屏障（BTB）保护的免疫特权曲细精管中，BTB破坏导致精子损伤和男性不育。因此，使用兔子喂养2%的胆固醇丰富的饮食2，4，和6周，以提高血浆胆固醇水平，我们测试的假设，血浆胆固醇水平升高破坏BTB功能和生化。富含胆固醇的饮食显著增加了生精小管中的脂质沉积，并呈时间依赖性，破坏了BTB，如生精小管内IgG染色增加所证明的。总蛋白质水平的紧密连接蛋白ZO-1和occludin的兔子饲养的富含胆固醇的饮食的曲细精管中增加，和紧密连接蛋白的分布模式受到显着影响，包括增加的积累紧密连接蛋白的内涵体。由于血浆胆固醇水平升高而导致的BTB完整性的破坏可能在男性不育中起作用。
About 15% of heterosexual couples in the USA suffer from infertility issues; male infertility accounts for similar to 50% of all infertility cases and roughly 50% of male infertility is idiopathic. Increased levels of plasma cholesterol affect spermatogenesis and male fertility negatively, but by unclear mechanisms. Clearly, spermatogenesis occurs in immune-privileged seminiferous tubules that are protected by the blood-testis barrier (BTB), and BTB disruption results in sperm damage and male infertility. Accordingly, using rabbits fed a 2% cholesterol-enriched diet for 2, 4, and 6 wk to raise levels of plasma cholesterol, we tested the hypothesis that elevated levels of plasma cholesterol disrupt the BTB functionally and biochemically. The cholesterol-enriched diet increased lipid deposition dramatically and time-dependently in the seminiferous tubules and disrupted the BTB as evidenced by increased IgG staining within the seminiferous tubules. Total protein levels of the tight-junction proteins ZO-1 and occludin were increased in the seminiferous tubules of rabbits fed the cholesterol-enriched diet, and the distribution patterns of tight-junction proteins were markedly affected, including an increased accumulation of tight-junction proteins in endosomes. Disruption of the integrity of the BTB due to increased plasma levels of cholesterol might play a role in male infertility.