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  • Title: BPA disrupts the SC barrier integrity by activating the cytokines/JNK signaling pathway in rare minnow Gobiocypris rarus.
    Author: Zhu L, Guan Y, Li X, Xiong X, Liu J, Wang Z.
    Journal: Aquat Toxicol; 2022 Apr; 245():106124. PubMed ID: 35193009.
    Abstract:
    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.
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