Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences,Bratislava, Slovakia.
Endocr Regul. 2020 Nov 24;54(4):275-283. doi: 10.2478/enr-2020-0031.
Bisphenol A (BPA), as an indispensable plastic additive, has also been proven as an endocrine disruptor associated with adverse health effects including impaired ovarian function and cancer. Due to the restrictions of its usage, several analogs have been employed to replace BPA. Although many studies revealed a harmfulness in the biological effects of BPA analogs, their specific targets remain largely unknown. Nuclear receptors (NRs) may be one of the most important targets of bisphenols. Therefore, in this study, our attention was directed to explore the effect of BPA and its analogs, AF and S, on the mRNA expression of selected NRs involved in the steroidogenic and carcinogenic pathways in the human granulosa cell line COV434. The NRs investigated included: thyroid hormone receptor α (THRA), peroxisome proliferator activating receptor β/δ (PPARD), retinoid X receptor α (RXRA), chicken ovalbumin upstream promoter-transcription factor II (COUPTFII), nuclear receptor-related protein 1 (NURR1), and liver receptor homolog-1 (LRH1). COV434 cells were treated with the bisphenols at the concentrations of 10 M, 10 M, and 10 M, and after 24 and 48 h, cell viability was monitored by the MTS assay and gene expressions were analyzed using RT-qPCR. Bisphenol treatment did not alter the COV434 cell viability. After 24 h, the expression of neither of the NRs was changed. Likewise, after 48 h, the expression of the selected genes was not altered. However, both BPAF and BPS increased, at the highest concentration (10 M) used, the mRNA levels of both and NRs after 48 h of the treatment. In the BPA-treated groups, no significant upregulation was observed. In the present study, the effect of bisphenols on COUP-TFII, Nurr1, and LRH-1 NRs was investigated for the first time. Although generally we did not observe that BPs provoked any alterations in the expression of the selected NRs in COV434 cells, at specific concentrations and time points they might alter mRNA expression of certain NRs (, ).
双酚 A（BPA）作为一种不可或缺的塑料添加剂，已被证明是一种内分泌干扰物，与卵巢功能障碍和癌症等不良健康影响有关。由于其使用受到限制，因此已经采用了几种类似物来替代 BPA。尽管许多研究揭示了 BPA 类似物在生物学效应方面的危害性，但它们的具体靶标在很大程度上仍不清楚。核受体（NRs）可能是双酚类物质的最重要靶标之一。因此，在这项研究中，我们的注意力集中在探索 BPA 及其类似物 AF 和 S 对参与甾体生成和致癌途径的选定 NRs 的 mRNA 表达的影响，这些 NRs 在人颗粒细胞系 COV434 中。所研究的 NRs 包括：甲状腺激素受体α（THRA）、过氧化物酶体增殖物激活受体β/δ（PPARD）、视黄醇 X 受体α（RXRA）、鸡卵清蛋白上游启动子转录因子 II（COUPTFII）、核受体相关蛋白 1（NURR1）和肝受体同系物 1（LRH1）。将双酚类化合物以 10 μM、10 μM 和 10 μM 的浓度处理 COV434 细胞，分别在 24 和 48 h 后通过 MTS 测定法监测细胞活力，并使用 RT-qPCR 分析基因表达。双酚处理不会改变 COV434 细胞活力。在 24 h 时，NRs 的表达均未改变。同样，在 48 h 后，所选基因的表达未改变。但是，在用最高浓度（10 μM）处理 48 h 后，BPAF 和 BPS 均增加了 和 NRs 的 mRNA 水平。在 BPA 处理组中，未观察到明显的上调。在本研究中，首次研究了双酚类化合物对 COUP-TFII、Nurr1 和 LRH-1 NRs 的影响。尽管我们通常没有观察到 BPs 会引起 COV434 细胞中选定 NRs 的表达发生任何变化，但在特定浓度和时间点，它们可能会改变某些 NRs 的 mRNA 表达（，）。
