ZeClinics SL, Carretera de Can Ruti, Camí de les Escoles, s/n, Edificio IGTP Muntanya, Badalona, 08916 Barcelona, Spain.
Int J Mol Sci. 2019 Apr 8;20(7):1739. doi: 10.3390/ijms20071739.
Small fish are an excellent experimental model to screen endocrine-disrupting compounds, but current fish-based assays to detect endocrine disruption have not been standardized yet, meaning that there is not consensus on endpoints and biomarkers to be measured. Moreover, exposure conditions may vary depending on the species used as the experimental model and the endocrine pathway evaluated. At present, a battery of a wide range of assays is usually needed for the complete assessment of endocrine activities. With the aim of providing a simple, robust, and fast assay to assess endocrine-disrupting potencies for the three major endocrine axes, i.e., estrogens, androgens, and thyroid, we propose the use of a panel of eight gene expression biomarkers in zebrafish larvae. This includes brain aromatase (cyp19a1b) and vitellogenin 1 (vtg1) for estrogens, cytosolic sulfotransferase 2 family 2 (sult2st3) and cytochrome P450 2k22 (cyp2k22) for androgens, and thyroid peroxidase (tpo), transthyretin (ttr), thyroid receptor α (trα), and iodothyronine deiodinase 2 (dio2) for thyroid metabolism. All of them were selected according to their responses after exposure to the natural ligands 17β-estradiol, testosterone, and 3,3',5-triiodo-L-thyronine (T3), respectively, and subsequently validated using compounds reported as endocrine disruptors in previous studies. Cross-talk effects were also evaluated for all compounds.
小鱼是筛选内分泌干扰化合物的优秀实验模型，但目前用于检测内分泌干扰的鱼类检测方法尚未标准化，这意味着在需要测量的终点和生物标志物方面尚未达成共识。此外，暴露条件可能因用作实验模型的物种和评估的内分泌途径而有所不同。目前，通常需要一系列广泛的检测来全面评估内分泌活性。为了提供一种简单、稳健、快速的检测方法来评估三种主要内分泌轴（雌激素、雄激素和甲状腺）的内分泌干扰潜力，我们建议在斑马鱼幼虫中使用一组 8 个基因表达生物标志物。这包括脑芳香酶（cyp19a1b）和卵黄蛋白原 1（vtg1）用于雌激素，细胞质磺基转移酶 2 家族 2（sult2st3）和细胞色素 P450 2k22（cyp2k22）用于雄激素，以及甲状腺过氧化物酶（tpo）、转甲状腺素蛋白（ttr）、甲状腺受体α（trα）和碘甲状腺原氨酸脱碘酶 2（dio2）用于甲状腺代谢。所有这些都是根据它们暴露于天然配体 17β-雌二醇、睾酮和 3,3',5-三碘-L-甲状腺素（T3）后的反应选择的，随后使用先前研究中报道的作为内分泌干扰物的化合物进行了验证。还评估了所有化合物的交叉对话效应。
