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Disruption of the blood-testis barrier integrity by bisphenol A in vitro: Is this a suitable model for studying blood-testis barrier dynamics?

机译：双酚a体外破坏血睾屏障完整性：这是研究血睾屏障动力学的合适模型吗？

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Bisphenol A, an estrogenic environmental toxicant, has been implicated to have hazardous effects on reproductive health in humans and rodents. However, there are conflicting reports in the literature regarding its effects on 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 in vitro, which can also serve as a suitable model for studying the dynamics of the blood-testis barrier. © 2009 Elsevier Ltd. All rights reserved.
机译：双酚A是一种雌激素性环境毒物，被认为对人类和啮齿动物的生殖健康具有有害影响。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的成年大鼠中，睾丸中生精小管的小但统计学上无意义的百分比显示出生殖细胞损失的迹象，这与一些早期报道一致。它还不能破坏体内的血液-睾丸屏障。这可能是由于游离双酚A在体循环中的生物利用度低。但是，双酚A给予未成熟20天大的大鼠给药时会破坏血睾屏障，这与早期有关未成熟大鼠对双酚A的敏感性较高的报道一致。这一观察结果已通过体外培养的原代支持细胞在密闭条件下进行了证实。在体内模拟血液-睾丸屏障的连接渗透性屏障。双酚A对Sertoli细胞紧密连接屏障的可逆破坏与ERK的激活有关，并且紧密连接，基础胞浆特化和血液-睾丸屏障的间隙连接处的所选蛋白质水平下降。通过双标记免疫荧光分析和生物素化技术进行的研究还表明，双酚A处理后在细胞-细胞界面上的闭合蛋白，连接蛋白43和N-钙黏着蛋白水平下降。总之，双酚A可逆地干扰体外Sertoli细胞中血液-睾丸屏障的完整性，这也可以用作研究血液-睾丸屏障动力学的合适模型。 ©2009 ElsevierLtd。保留所有权利。

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