Quantitative proteomic changes in the liver of adult males of Sheepshead minnow (Cyprinodon variegatus) upon exposure to ethinyl estradiol (EE2) were assessed to provide an advanced understanding of the metabolic pathways affected by estrogenic endocrine disruption in marine fish, and to identify potential novel molecular biomarkers for the environmental exposure to estrogens. From a total of 3188 identified protein groups (hereafter proteins), 463 showed a statistically significant difference in their abundance between EE2 treatment and solvent control samples. The most affected biological processes upon EE2 exposure were related to ribosomal biogenesis, protein synthesis and transport of nascent proteins to endoplasmic reticulum, and nuclear mRNA catabolism. Within the group of upregulated proteins, a subset of 14 proteins, involved in egg production (Vitellogenin, Zona Pellucida), peptidase activity (Cathepsine E, peptidase S1, Serine/threonine-protein kinase PRP4 homolog, Isoaspartyl peptidase and Whey acidic protein), and nucleic acid binding (Poly [ADP-ribose] polymerase 14) were significantly upregulated with fold-change values higher than 3. In contrast, Collagen alpha-2, involved in the process of response to steroid hormones, among others, was significantly downregulated (fold change = 0.2). This pattern of alterations in the liver proteome of adult males of C. variegatus can be used to identify promising novel biomarkers for the characterization of exposure of marine fish to estrogens. The Whey acidic protein-like showed the highest upregulation in EE2-exposed individuals (21-fold over controls), suggesting the utility of abundance levels of this protein in male liver as a novel biomarker of xenoestrogen exposure.

成年雄性羊头鲦（ Cyprinodon variegatus）肝脏的定量蛋白质组学变化) 在暴露于乙炔雌二醇 (EE2) 后进行评估，以提供对受海洋鱼类雌激素内分泌干扰影响的代谢途径的深入了解，并确定环境暴露于雌激素的潜在新分子生物标志物。从总共 3188 个确定的蛋白质组（以下称为蛋白质）中，463 个在 EE2 处理和溶剂对照样品之间的丰度上显示出统计学上的显着差异。EE2 暴露后受影响最大的生物过程与核糖体生物发生、蛋白质合成和新生蛋白质向内质网的转运以及核 mRNA 分解代谢有关。在上调的蛋白质组中，14 种蛋白质的一个子集，参与产卵（卵黄原蛋白、透明带）、肽酶活性（组织蛋白酶 E、肽酶 S1、丝氨酸/苏氨酸蛋白激酶 PRP4 同源物、异天冬氨酰肽酶和乳清酸性蛋白）和核酸结合（聚 [ADP-核糖] 聚合酶 14）显着上调，倍数变化值高于 3。相比之下，胶原蛋白 alpha-2 ，参与对类固醇激素的反应过程等，显着下调（倍数变化 = 0.2）。成年男性肝脏蛋白质组的这种变化模式C. variegatus可用于鉴定有前景的新型生物标志物，用于表征海洋鱼类暴露于雌激素的情况。乳清酸性蛋白样在 EE2 暴露的个体中表现出最高的上调（比对照组高 21 倍），这表明这种蛋白质在男性肝脏中的丰度水平可用作异种雌激素暴露的新生物标志物。