Abstract：
Natural and synthetic environmental estrogens (EEs) are widespread and have received extensive attention. Our previous studies demonstrated that depletion of the cytochrome P450 17a1 gene (cyp17a1) leads to all-testis differentiation phenotype in zebrafish and common carp. In the present study, cyp17a1-deficient zebrafish with defective estrogen biosynthesis were used for the evaluation of EEs, as assessed by monitoring vitellogenin (vtg) expression. A rapid and sensitive assessment procedure was established with the 3-day administration of estradiol (E2), followed by examination of the transcriptional expression of vtgs in our cyp17a1-deficient fish. Compared with the control fish, a higher E2-mediated vtg upregulation observed in cyp17a1-deficient zebrafish exposed to 0.1 μg/L E2 is known to be estrogen receptor-dependent and likely due to impaired in vivo estrogen biosynthesis. The more responsive vtg expression in cyp17a1-deficient zebrafish was observed when exposed to 200 and 2000 μg/L bisphenol A (BPA) and perfluoro-1-octanesulfonate (PFOS). The estrogenic potentials of E2, BPA, and PFOS were compared and assessed by the feminization effect on ovarian differentiation in cyp17a1-deficient zebrafish from 18 to 50 days postfertilization, based on which a higher sensitivity of E2 in ovarian differentiation than BPA and PFOS was concluded. Collectively, through the higher sensitivity to EEs and the capacity to distinguish chemicals with different estrogenic potentials exhibited by the all-male cyp17a1-deficient zebrafish with impaired estrogen biosynthesis, we demonstrated that they can be used as an excellent in vivo model for the evaluation of EEs. Environ Toxicol Chem 2024;43:1062-1074. © 2024 SETAC.
摘要：
天然和合成环境雌激素（EEs）广泛存在，受到广泛关注。我们先前的研究表明，细胞色素P45017a1基因（cyp17a1）的耗竭导致斑马鱼和鲤鱼的全睾丸分化表型。在本研究中,cyp17a1缺乏雌激素生物合成缺陷的斑马鱼用于评估EEs，通过监测卵黄蛋白原(vtg)表达来评估。通过3天的雌二醇（E2）给药建立了快速敏感的评估程序，然后检查我们的cyp17a1缺陷鱼中vtgs的转录表达。与对照鱼相比，已知在暴露于0.1μg/LE2的cyp17a1缺陷斑马鱼中观察到的更高的E2介导的vtg上调是雌激素受体依赖性的，并且可能是由于体内雌激素生物合成受损。当暴露于200和2000μg/L的双酚A（BPA）和全氟-1-辛烷磺酸盐（PFOS）时，在cyp17a1缺陷型斑马鱼中观察到更敏感的vtg表达。E2、BPA、和全氟辛烷磺酸在受精后18至50天对cyp17a1缺陷斑马鱼卵巢分化的女性化效应进行比较和评估，据此得出结论，E2在卵巢分化中的敏感性高于BPA和PFOS。总的来说，通过对EEs的更高敏感性和区分雌激素生物合成受损的全雄性cyp17a1缺陷斑马鱼所表现出的具有不同雌激素潜能的化学物质的能力，我们证明了它们可以用作评估EEs的出色体内模型。环境毒物化学2024；43：1062-1074。©2024SETAC。
