CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Endocrine Disruptors and Emerging Contaminants Group, University of Porto, Avenida General Norton de Matos S/N, 4450-208 Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre nº 1021/1055, 4169-007 Porto, Portugal.
CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Endocrine Disruptors and Emerging Contaminants Group, University of Porto, Avenida General Norton de Matos S/N, 4450-208 Matosinhos, Portugal.
Ecotoxicol Environ Saf. 2021 Feb;209:111849. doi: 10.1016/j.ecoenv.2020.111849. Epub 2020 Dec 30.
The adverse effects of certain environmental chemicals have been recently associated with the modulation of the epigenome. Although changes in the epigenetic signature have yet to be integrated into hazard and risk assessment, they are interesting candidates to link environmental exposures and altered phenotypes, since these changes may be passed across multiple non-exposed generations. Here, we addressed the effects of simvastatin (SIM), one of the most prescribed pharmaceuticals in the world, on epigenetic regulation using the amphipod Gammarus locusta as a proxy, to support its integration into hazard and environmental risk assessment. SIM is a known modulator of the epigenome in mammalian cell lines and has been reported to impact G. locusta ecological endpoints at environmentally relevant levels. G. locusta juveniles were exposed to three SIM environmentally relevant concentrations (0.32, 1.6 and 8 µg L) for 15 days. Gene transcription levels of selected epigenetic regulators, i.e., dnmt1, dmap1, usp7, kat5 and uhrf1 were assessed, along with the quantification of DNA methylation levels and evaluation of key ecological endpoints: survival and growth. Exposure to 0.32 and 8 µg L SIM induced significant downregulation of DNA methyltransferase 1 (dnmt1), concomitant with global DNA hypomethylation and growth impacts. Overall, this work is the first to validate the basal expression of key epigenetic regulators in a keystone marine crustacean, supporting the integration of epigenetic biomarkers into hazard assessment frameworks.
最近，某些环境化学物质的不良影响与表观基因组的调节有关。尽管表观遗传特征的变化尚未纳入危害和风险评估，但它们是将环境暴露与表型改变联系起来的有趣候选者，因为这些变化可能会在多个未暴露的世代中传递。在这里，我们使用溞作为模型，研究了辛伐他汀（SIM）对表观遗传调控的影响，SIM 是世界上使用最广泛的药物之一，旨在支持将其纳入危害和环境风险评估。SIM 是哺乳动物细胞系中已知的表观遗传调节剂，并且据报道，它会在环境相关水平上影响 G. locusta 的生态终点。将 G. locusta 幼体暴露于三种环境相关浓度的 SIM（0.32、1.6 和 8 µg/L）15 天。评估了选定的表观遗传调节剂（dnmt1、dmap1、usp7、kat5 和 uhrf1）的基因转录水平，以及 DNA 甲基化水平的定量和关键生态终点的评估：存活和生长。暴露于 0.32 和 8 µg/L SIM 会诱导 DNA 甲基转移酶 1（dnmt1）的显著下调，同时伴随着全基因组低甲基化和生长影响。总的来说，这项工作首次验证了关键海洋甲壳类动物中表观遗传调节剂的基础表达，支持将表观遗传生物标志物纳入危害评估框架。
