Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada.
Ecotoxicology and Wildlife Health Division, National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, Ontario, Canada.
Environ Toxicol Chem. 2022 Nov;41(11):2769-2781. doi: 10.1002/etc.5464. Epub 2022 Sep 30.
Chemical risk assessment for avian species typically depends on information from toxicity tests performed in adult birds. Early-life stage (ELS) toxicity tests have been proposed as an alternative, but incorporation of these data into existing frameworks will require knowledge about the similarities/differences between ELS and adult responses. The present study uses transcriptomics to assess hepatic gene expression in ELS and adult Japanese quail following exposure to ethinylestradiol (EE2). Prior to incubation, ELS quail were dosed with measured EE2 concentrations of 0.54, 6.3, and 54.2 µg/g egg weight via air cell injection. Adult quail were fed a single dose of EE2 at nominal concentrations of 0, 0.5, and 5 mg/kg body weight by gavage. Liver tissue was collected from five to six individuals per dose group at mid-incubation for ELS quail and 4 days after dosing for adults. A total of 283 and 111 differentially expressed genes (DEGs) were detected in ELS and adult quail, respectively, 16 of which were shared across life stages. Shared DEGs included estrogenic biomarkers such as vitellogenin genes and apovitellenin-1. For the dose groups that resulted in the highest number of DEGs (ELS, 6.3 µg/g; adult, 5 mg/kg), 21 and 35 Kyoto Encyclopedia of Genes and Genomes pathways were enriched, respectively. Ten of these pathways were shared between life stages, including pathways involved with signaling molecules and interaction and the endocrine system. Taken together, our results suggest conserved mechanisms of action following estrogenic exposure across two life stages, with evidence from differential expression of key biomarker genes and enriched pathways. The present study contributes to the development and evaluation of ELS tests and toxicogenomic approaches and highlights their combined potential for screening estrogenic chemicals. Environ Toxicol Chem 2022;41:2769-2781. © 2022 SETAC.
鸟类物种的化学风险评估通常依赖于对成年鸟类进行的毒性测试信息。早期生命阶段（ELS）毒性测试已被提议作为替代方法，但将这些数据纳入现有框架将需要了解 ELS 和成年反应之间的相似之处/差异。本研究使用转录组学来评估暴露于乙炔雌二醇（EE2）后 ELS 和成年日本鹌鹑的肝基因表达。在孵化之前，ELS 鹌鹑通过气室注射接受测量的 EE2 浓度为 0.54、6.3 和 54.2 µg/g 卵重的剂量。成年鹌鹑通过灌胃以 0、0.5 和 5 mg/kg 体重的名义浓度给予 EE2 单次剂量。ELS 鹌鹑在孵化中期和成年鹌鹑在给药后 4 天，从每个剂量组的五到六个人收集肝脏组织。在 ELS 和成年鹌鹑中分别检测到 283 和 111 个差异表达基因（DEG），其中 16 个在两个生命阶段共享。共享的 DEG 包括卵黄蛋白原基因和卵黄蛋白原-1 等雌激素生物标志物。对于导致 DEG 数量最多的剂量组（ELS，6.3 µg/g；成年，5mg/kg），分别富集了 21 和 35 个京都基因与基因组百科全书通路。这些通路中有 10 个在两个生命阶段之间共享，包括涉及信号分子和相互作用以及内分泌系统的途径。总的来说，我们的结果表明，在两个生命阶段暴露于雌激素后存在保守的作用机制，证据来自关键生物标志物基因的差异表达和富集的途径。本研究为 ELS 测试和毒理基因组学方法的发展和评估做出了贡献，并强调了它们在筛选雌激素化学物质方面的综合潜力。环境毒物化学 2022；41:2769-2781。© 2022 SETAC。
