Disruption of the blood-testis barrier integrity by bisphenol A in vitro: is this a suitable model for studying blood-testis barrier dynamics?
Disruption of the blood-testis barrier integrity by bisphenol A in vitro: is this a suitable model for studying blood-testis barrier dynamics?
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DOI：
10.1016/j.biocel.2009.05.016
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发表时间：
2009-11
影响因子：
4
通讯作者：
Cheng, C. Yan
中科院分区：
文献类型：
--
作者：
Li, Michelle W. M.;Mruk, Dolores D.;Lee, Will M.;Cheng, C. Yan
关键词：
双酚A是一种雌激素环境毒物，对人类和啮齿类动物的生殖健康有危害作用。然而，关于其对男性生殖功能的影响，文献中有相互矛盾的报道。在这项研究中，研究表明，在接受急性剂量双酚A治疗的成年大鼠中，睾丸中小但统计学上不显著的生精小管百分比显示出生殖细胞损失的迹象，与一些早期报告一致。它也未能破坏体内血睾屏障。这可能是由于游离双酚A在体循环中的生物利用度低。然而，双酚A对未成熟的20日龄大鼠给药时破坏了血-睾丸屏障，这与早期关于未成熟大鼠对双酚A更敏感的报道一致。使用体外培养的原代支持细胞证实了这一观察结果，该细胞具有模仿体内血-睾丸屏障的紧密连接-渗透性屏障。支持细胞紧密连接屏障的可逆性破坏双酚A与ERK的激活，并在紧密连接，基底细胞外质特化，和血-睾丸屏障的间隙连接的选定蛋白质的水平下降。通过双标记免疫荧光分析和生物素化技术的研究也说明了双酚A处理后细胞-细胞界面处闭合蛋白、连接蛋白43和N-钙粘蛋白的水平下降。总之，双酚A可逆地扰乱了支持细胞中血睾屏障的完整性，这也可以作为研究血睾屏障动力学的合适模型。
Bisphenol A, an estrogenic environmental toxicant, has been implicated to have hazardous effects to reproductive health in humans and rodents. However, there are conflicting reports in the literature regarding its effects to male reproductive function. In this study, it was shown that in adult rats treated with acute doses of bisphenol A, a small but statistically insignificant percentage of seminiferous tubules in the testes displayed signs of germ cell loss, consistent with some earlier reports. It also failed to disrupt the blood-testis barrier in vivo. This is possibly due to the low bioavailability of free bisphenol A in the systemic circulation. However, bisphenol A disrupted the blood-testis barrier when administered to immature 20-day-old rats, consistent with earlier reports concerning the higher susceptibility of immature rats towards bisphenol A. This observation was confirmed using primary Sertoli cells cultured in vitro with established tight junction-permeability barrier that mimicked the blood-testis barrier in vivo. The reversible disruption of Sertoli cell tight junction barrier by bisphenol A was associated with an activation of ERK, and a decline in the levels of selected proteins at the tight junction, basal ectoplasmic specialization, and gap junction at the blood-testis barrier. Studies by dual-labeled immunofluorescence analysis and biotinylation techniques also illustrated declining levels of occludin, connexin 43, and N-cadherin at the cell-cell interface following bisphenol A treatment. In summary, bisphenol A reversibly perturbs the integrity of the blood-testis barrier in Sertoli cells, which can also serve as a suitable model for studying the dynamics of the blood-testis barrier.
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DOI：
10.1038/jes.2008.20
发表时间：
2008-11-01
影响因子：
4.5
作者：
Lakind, Judy S.;Naiman, Daniel Q.
通讯作者：
Naiman, Daniel Q.
影响因子：
4.5
作者：
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DOI：
10.1073/pnas.0506084102
发表时间：
2005-11-15
影响因子：
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作者：
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通讯作者：
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影响因子：
4.9
作者：
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通讯作者：
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影响因子：
4.8
作者：
Chung, NPY;Cheng, CY
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