Ayobahan Steve U, Alvincz Julia, Reinwald Hannes, Strompen Jannis, Salinas Gabriela, Schäfers Christoph, Eilebrecht Elke, Eilebrecht Sebastian
Fraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, Germany.
Fraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, Germany; Department Evolutionary Ecology and Environmental Toxicology, Faculty Biological Sciences, Goethe University Frankfurt, Frankfurt, Germany.
Ecotoxicol Environ Saf. 2023 Jan 15;250:114514. doi: 10.1016/j.ecoenv.2023.114514. Epub 2023 Jan 4.
Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory testing to evaluate endocrine disruption is time-consuming, costly, and animal-intensive. Here, we combined sublethal zebrafish embryo assays with transcriptomics and proteomics for well-characterized endocrine disrupting reference compounds to identify predictive biomarkers for sexual endocrine disruption in this model. Using RNA and protein gene expression fingerprints from two different sublethal exposure concentrations, we identified specific signatures and impaired biological processes induced by ethinylestradiol, tamoxifen, methyltestosterone and flutamide 96 h post fertilization (hpf). Our study promotes vtg1 as well as cyp19a1b, fam20cl, lhb, lpin1, nr1d1, fbp1b, and agxtb as promising biomarker candidates for identifying and differentiating estrogen and androgen receptor agonism and antagonism. Evaluation of these biomarkers for pre-regulatory zebrafish embryo-based bioassays will help identify endocrine disrupting hazards of compounds at the molecular level. Such approaches additionally provide weight-of-evidence for the identification of putative EDs and may contribute significantly to a reduction in animal testing in higher tier studies.
内分泌干扰物（EDs）能够调节生物体的性激素系统，会对人类和环境的生殖产生长期负面影响。由于这些原因，EDs的特性使得一种物质无法被批准上市。然而，评估内分泌干扰的监管测试耗时、成本高且需要大量动物。在此，我们将斑马鱼胚胎亚致死试验与转录组学和蛋白质组学相结合，用于特征明确的内分泌干扰参考化合物，以确定该模型中性内分泌干扰的预测生物标志物。利用来自两种不同亚致死暴露浓度的RNA和蛋白质基因表达指纹图谱，我们确定了受精后96小时（hpf）时乙炔雌二醇、他莫昔芬、甲基睾酮和氟他胺诱导的特定特征和受损的生物学过程。我们的研究将vtg1以及cyp19a1b、fam20cl、lhb、lpin1、nr1d1、fbp1b和agxtb作为识别和区分雌激素和雄激素受体激动作用及拮抗作用的有前景的生物标志物候选物。对这些生物标志物进行基于斑马鱼胚胎的预监管生物测定评估，将有助于在分子水平上识别化合物的内分泌干扰危害。此类方法还为识别推定的EDs提供了证据权重，并可能对减少高级研究中的动物试验做出重大贡献。
