Bisphenol-A (BPA) has been reported to disrupt blood-testis barrier (BTB) integrity in mammals. However, its effects on fish testis sertoli cell (SC) barrier and the underlying mechanisms have been largely unknown to date. To study the SC barrier toxicity induced by BPA, male rare minnows (Gobiocypris rarus) were exposed to 15 μg L ^− 1 BPA for 7, 14 and 21 d. Meanwhile, a 25 ng L⁻¹ 17α-ethynyl estradiol (EE2) group was set up as the positive control. Results showed that BPA induced immune response in the testes and decreased offspring hatching rate. The biotin tracer assay showed that BPA exposure destroyed the integrity of the testis SC barrier. In addition, BPA exposure decreased the expressions of occludin, ZO-1, CX43 and N-cadherin proteins. The transcripts of CX43 and occludin were significantly decreased and SP1 recruitment in each gene promoter was repressed after BPA exposure. Moreover, the cytokines (TNFα and IL-1β) were significantly increased while the JNK signal pathway was activated after BPA exposure. BPA also increased the matrix metalloproteinases 1 (MMP1) and MMP2 levels in the testes. In addition, estrogenic effect did not entirely explain the mechanism by which BPA disrupted the SC barrier in G. rarus testes. These results suggested that BPA disrupted the SC barrier integrity by inhibiting SP1 enrichments within CX43 and occludin 5′ flanking regions through activated cytokines/JNK signaling pathway. MMPs were also involved in the disruption of SC barrier caused by BPA exposure.

据报道，双酚 A (BPA) 会破坏哺乳动物的血睾丸屏障 (BTB) 完整性。然而，迄今为止，它对鱼类睾丸支持细胞 (SC) 屏障的影响及其潜在机制在很大程度上是未知的。为了研究 BPA 诱导的 SC 屏障毒性，雄性稀有鲦鱼 ( Gobiocypris rarus ) 暴露于 15 μg L  ^{-  1} BPA 7、14 和 21 天。同时，25 ng L ^-117α-乙炔雌二醇(EE2)组作为阳性对照。结果表明，BPA 在睾丸中诱导免疫反应并降低后代孵化率。生物素示踪剂测定表明，BPA 暴露破坏了睾丸 SC 屏障的完整性。此外，BPA 暴露降低了 occludin、ZO-1、CX43 和 N-cadherin 蛋白的表达。CX43和occludin的转录本显着降低，并且在 BPA 暴露后，每个基因启动子中的 SP1 募集被抑制。此外，当 JNK 信号通路在 BPA 暴露后被激活时，细胞因子（TNFα 和 IL-1β）显着增加。BPA 还增加了睾丸中的基质金属蛋白酶 1 (MMP1) 和 MMP2 水平。此外，雌激素效应并不能完全解释 BPA 破坏G. rarus睾丸 SC 屏障的机制。这些结果表明，BPA通过激活的细胞因子/JNK 信号通路抑制CX43和occludin 5' 侧翼区域内的 SP1 富集，从而破坏了 SC 屏障的完整性。MMPs 也参与了由 BPA 暴露引起的 SC 屏障的破坏。