Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China; College of Oceanography, Hohai University, Nanjing 210098, China.
Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China.
Sci Total Environ. 2022 Feb 25;809:151103. doi: 10.1016/j.scitotenv.2021.151103. Epub 2021 Oct 29.
In our previous studies, it was found that graphene oxide (GO) reduced the endocrine disruption of bisphenol A (BPA) in zebrafish embryo and larvae, but through different mechanisms. In this study, adult male zebrafish were selected to further understand the interactions between GO and BPA considering that adult zebrafish have different uptake pathways and metabolism from embryo and larvae. BPA was predicted to bind with the estrogen receptor α (ERα) with a probability of 98.1% by training a directed-message passing deep neural network model, and was confirmed by molecular docking analysis. The results were in accordance with the significantly increased vitellogenin (VTG) and estradiol (E2) levels, while decreased testosterone (T) and follicle-stimulating hormone (FSH) levels in the adult male zebrafish after 7 d exposure to 500 μg/L BPA. Compared to BPA single exposure group, the presence of GO led to significantly lower T and FSH levels and fewer spermatozoa, indicating that GO enhanced the endocrine disruption effects of BPA in the adult zebrafish. Metabolomics analysis revealed that 5 μg/L BPA could elicit changes in the metabolome, and the responses were correlated with BPA concentrations. Metabolic pathway analysis revealed more disturbance was caused by the mixture of GO and BPA compared to BPA alone, including three additional pathways and stronger perturbations on carbohydrate, lipid, and amino acid metabolism, fortifying that GO exaggerated the toxic effects of BPA. This was opposite to the depression effect observed in zebrafish embryo and larvae, magnifying that the joint effects of exposure to nanomaterials and endocrine disrupting chemicals are relevant to the life stages of organisms.
在我们之前的研究中发现，氧化石墨烯（GO）可降低双酚 A（BPA）对斑马鱼胚胎和幼鱼的内分泌干扰，但作用机制不同。在这项研究中，选择成年雄性斑马鱼来进一步了解 GO 和 BPA 之间的相互作用，因为成年斑马鱼的摄取途径和代谢与胚胎和幼鱼不同。通过训练有向消息传递深度神经网络模型，预测 BPA 与雌激素受体 α（ERα）的结合概率为 98.1%，并通过分子对接分析得到证实。结果与 500μg/L BPA 暴露 7 天后成年雄性斑马鱼中卵黄蛋白原（VTG）和雌二醇（E2）水平显著升高，而睾酮（T）和促卵泡激素（FSH）水平降低的结果一致。与 BPA 单一暴露组相比，GO 的存在导致 T 和 FSH 水平显著降低，精子数量减少，表明 GO 增强了 BPA 对成年斑马鱼的内分泌干扰作用。代谢组学分析显示，5μg/L BPA 可引起代谢组发生变化，并且这些反应与 BPA 浓度相关。代谢途径分析显示，GO 和 BPA 的混合物比 BPA 单独引起更多的干扰，包括另外三个途径以及对碳水化合物、脂质和氨基酸代谢的更强干扰，进一步证实 GO 夸大了 BPA 的毒性作用。这与在斑马鱼胚胎和幼鱼中观察到的抑制作用相反，凸显了暴露于纳米材料和内分泌干扰化学物质的联合效应与生物体的生命阶段有关。
