Sertoli cell is a potential target for perfluorooctane sulfonate-induced reproductive dysfunction in male mice.
Sertoli cell is a potential target for perfluorooctane sulfonate-induced reproductive dysfunction in male mice.
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DOI：
10.1093/toxsci/kft129
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Lianglin Qiu;Xu-hui Zhang;Xiaoming Zhang;Yudong Zhang;Jun Gu;Minjian Chen;Zhan Zhang;Xinru Wang-Xinr
中科院分区：
文献类型：
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作者：
Lianglin Qiu;Xu-hui Zhang;Xiaoming Zhang;Yudong Zhang;Jun Gu;Minjian Chen;Zhan Zhang;Xinru Wang-Xinr
全氟辛烷磺酸（PFOS）与男性生殖障碍有关，但对其目标和机制知之甚少。我们采用体外和体内模型来探讨支持细胞和血睾屏障（BTB）在全氟辛烷磺酸诱导的男性生殖功能障碍中的作用。首先，我们使用原代支持细胞来评估全氟辛烷磺酸诱导的细胞毒性，连接蛋白的表达，以及屏障功能的变化。然后对ICR小鼠注射PFOS（0.25- 50毫克/公斤/天），持续4周。对精子数量、超微结构和基于支持细胞的BTB和睾丸全氟辛烷磺酸的渗透性进行了估计。此外，支持细胞和丝裂原活化蛋白激酶（MAPK）信号通路之间的连接相关蛋白的表达和定位进行了评估。全氟辛烷磺酸显著增加了生精小管中支持细胞的空泡化和BTB超微结构的解体，随后增加了BTB的渗透性和睾丸的全氟辛烷磺酸水平，体外结果证实全氟辛烷磺酸降低了支持细胞之间的跨上皮电阻。此外，全氟辛烷磺酸降低了支持细胞中连接蛋白的表达，这一点进一步得到了体内结果的证实，即全氟辛烷磺酸降低了连接蛋白的表达或使其移位（即，ZO-1、闭合蛋白、紧密连接蛋白-11和连接蛋白-43）和与MAPK信号通路相关的蛋白质增加（即，ERK和p38），而基础的内质网专业化蛋白没有改变。p38 MAPK选择性抑制剂SB 203580证实了上述结果。支持细胞似乎是全氟辛烷磺酸的一个新的细胞靶点。这些细胞在破坏BTB的完整性和功能的同时，在全氟辛烷磺酸引起的雄性生殖毒性中发挥重要作用。
Perfluorooctane sulfonate (PFOS) is associated with male reproductive disorders, but its targets and mechanisms are poorly understood. We used in vitro and in vivo models to explore the roles of Sertoli cells and the blood-testis barrier (BTB) in PFOS-induced male reproductive dysfunction. First, we used primary Sertoli cell to estimate PFOS-induced cytotoxicity, junction proteins expression, and the changes of barrier function. ICR mice were then administered PFOS (0.25-50mg/kg/day) for 4 weeks. Sperm count, ultrastructure and permeability of the Sertoli cell-based BTB, and testicular PFOS were estimated. Furthermore, the expression and localization of proteins related to junctions between Sertoli cells and mitogen-activated protein kinase (MAPK) signaling pathway were evaluated. Apparent decreases in sperm count were found. PFOS significantly increased vacuolization in Sertoli cells in seminiferous tubules and BTB ultrastructural disassembly, which subsequently increased BTB permeability and testicular PFOS levels, which was confirmed by in vitro results that PFOS decreased transepithelial electrical resistance between Sertoli cells. Additionally, PFOS decreased the expression of junction proteins in Sertoli cells, which was further confirmed by in vivo results that PFOS decreased or dislocated junction proteins (i.e., ZO-1, occludin, claudin-11, and connexin-43) and increased proteins related to the MAPK signaling pathway (i.e., Erk and p38), whereas basal ectoplasmic specialization proteins did not change. The results were confirmed by SB203580, a p38 MAPK selective inhibitor. Sertoli cells appear to be a new cellular target for PFOS. Together with disruption of BTB integrity and function, these cells play an important role in PFOS-induced male reproductive toxicity.