Abstract:
Triphenyl phosphate (TPhP) is an organophosphate flame retardant and plasticizer that is added to a wide variety of consumer and industrial products. It is also a ubiquitous environmental pollutant. Exposure to TPhP has been shown to alter gene expression in metabolic and estrogenic signaling pathways in in vitro and in vivo models of a variety of species, and as such, is considered to be an endocrine disrupting chemical. Exposure to endocrine disrupting chemicals is increasingly being associated with changes to the epigenome, especially during embryonic development. The aim of this study was to evaluate whether TPhP exposure in aquatic ecosystems has the ability to alter the epigenome in two immortal cell lines derived from trout (Oncorhynchus mykiss). This study assessed whether 24 h exposure to TPhP resulted in changes to histone modification and DNA methylation profiles in steelhead trout embryonic cells and rainbow trout gill epithelial cells. Results show that several epigenetic modifications on histone H3 and DNA methylation are altered in the embryonic cells following TPhP exposure, but not in the gill epithelial cells. Specifically, histone H3 acetylation, histone H3 mono-methylation and global DNA methylation were found to be reduced. The alterations of these epigenetic modification profiles in the embryonic cells suggest that exposure to TPhP during fetal development may alter gene expression in the developing embryo, likely in metabolic and estrogenic pathways. The impacts to the epigenome determined in this study may even carry multigenerational detrimental effects on human and ecosystem health, which requires further investigation.
摘要:
磷酸三苯酯(TPhP)是一种有机磷酸酯阻燃剂和增塑剂,可添加到各种消费品和工业产品中。它也是一种普遍存在的环境污染物。在多种物种的体外和体内模型中,暴露于TPhP已被证明可以改变代谢和雌激素信号通路中的基因表达,因此,被认为是一种内分泌干扰化学物质。暴露于内分泌干扰化学物质越来越多地与表观基因组的变化有关,特别是在胚胎发育过程中。这项研究的目的是评估TPhP在水生生态系统中的暴露是否具有改变鳟鱼(Oncorhynchusmykiss)衍生的两种永生细胞系中表观基因组的能力。这项研究评估了暴露于TPhP的24小时是否会导致钢头鳟鱼胚胎细胞和虹鳟鱼g上皮细胞中组蛋白修饰和DNA甲基化谱的变化。结果表明,TPhP暴露后,胚胎细胞中组蛋白H3和DNA甲基化发生了一些表观遗传修饰,但不在ill上皮细胞中。具体来说,组蛋白H3乙酰化,发现组蛋白H3单甲基化和全局DNA甲基化减少。胚胎细胞中这些表观遗传修饰谱的改变表明,在胎儿发育过程中暴露于TPhP可能会改变发育中胚胎中的基因表达。可能在代谢和雌激素途径中。本研究中确定的对表观基因组的影响甚至可能对人类和生态系统健康产生多代有害影响。这需要进一步调查。