Centro de Investigación Mariña, Universidade de Vigo (CIM-UVigo), Vigo, Galicia, Spain; Department of Biochemistry, Genetics and Immunology, University of Vigo, Galicia, Spain.
Centro de Investigación Mariña, Universidade de Vigo (CIM-UVigo), Vigo, Galicia, Spain; Department of Ecology and Animal Biology, University of Vigo, Vigo, Galicia, Spain.
Environ Pollut. 2022 May 1;300:118936. doi: 10.1016/j.envpol.2022.118936. Epub 2022 Feb 3.
The toxicological status of bisphenol A (BPA) is under strong debate. Whereas in vitro it is an agonist of the estrogen receptor with a potency ca. 10-fold lower than the natural female hormone estradiol, in vivo exposure causes only mild effects at concentration thresholds environmentally not relevant and inconsistent among species. By using a proteomic approach, shotgun liver proteome analysis, we show that 7-d exposure to 10 μg/L of the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), and not the same exposure to the parental molecule BPA, alters the liver proteome of male Cyprinodon variegatus fish. Different physiological and environmental conditions leading to biotransformation of BPA to MBP may partly explain the conflicting results so far reported for in vivo BPA exposures. The pattern of alteration induced by MBP is similar to that caused by estradiol, and indicative of estrogenic endocrine disruption. MBP enhanced ribosomal activity, protein synthesis and transport, with upregulation of 91% of the ribosome-related proteins, and 12 proteins whose expression is regulated by estrogen-responsive elements, including vitellogenin and zona pellucida. Whey acidic protein (WAP) was the protein most affected by MBP exposure (FC = 68). This result points at WAP as novel biomarker for xenoestrogens.
双酚 A（BPA）的毒理学状况存在激烈争议。虽然在体外，它是雌激素受体的激动剂，其效力比天然女性激素雌二醇低约 10 倍，但在体内暴露于环境中不相关且在物种间不一致的浓度阈值下仅引起轻微影响。通过使用蛋白质组学方法，即 shotgun 肝蛋白质组分析，我们表明，7 天暴露于 10μg/L 的 BPA 代谢物 4-甲基-2,4-双（4-羟苯基）戊-1-烯（MBP），而不是相同的母体分子 BPA 暴露，会改变雄性 Cyprinodon variegatus 鱼的肝蛋白质组。导致 BPA 生物转化为 MBP 的不同生理和环境条件可能部分解释了迄今为止报道的体内 BPA 暴露的相互矛盾的结果。MBP 诱导的改变模式与雌二醇引起的改变模式相似，表明存在雌激素内分泌干扰。MBP 增强了核糖体活性、蛋白质合成和运输，上调了 91%的核糖体相关蛋白，以及 12 种受雌激素反应元件调节的蛋白质，包括卵黄蛋白原和透明带。乳清酸性蛋白（WAP）是受 MBP 暴露影响最大的蛋白（FC=68）。这一结果表明 WAP 是新型外源性雌激素生物标志物。
