Since the phasing out and eventual ban on the production of organohalogen flame retardants, the use of organophosphate flame retardants (OPFRs) has increased rapidly. This has led to the detection of OPFRs in various environments including the Arctic. Two of the most prevalent OPFRs found in the Arctic are tris(2-chloroisopropyl) phosphate (TCPP), and 2-ethylhexyl diphenyl phosphate (EHDPP). The impacts of exposure to OPFRs on Arctic organisms is poorly understood. The objective of the present study was to determine the effects of exposure to TCPP, EHDPP, and a mixture of OPFRs on gene expression patterns in Atlantic cod, Gadus morhua. Precision-cut liver slices from Atlantic cod in vitro were exposed to either TCPP or EHDPP alone or in a mixture and sampled at 2 different time points to quantify gene expression patterns using RNA sequencing. We exposed the liver slices to 2 concentrations of TCPP and EHDPP, one of which was chosen based on the levels found in the Arctic environment. The RNA sequencing results demonstrated differential expression of hundreds of genes in response to exposure. The genes representing cholesterol biosynthesis and lipid metabolism pathway were significantly enriched in all the treatment groups. Almost all the cholesterol biosynthesis genes were significantly down-regulated in response to OPFR exposure. The effects on these pathways could involve various physiological processes including reproduction, growth, and behavior as well as adaptation to changing temperatures. Membrane fluidity is an important adaptive mechanism among aquatic organisms. Altered cholesterol homeostasis could have long-term consequences by altering the adaptive potential of aquatic organisms to changing water temperatures, particularly those living in polar environments. These results suggest that OPFRs could have unique effects on the organisms living in the Arctic compared with other environments. Further studies are needed to understand the long-term impacts of exposure to environmentally realistic concentrations using laboratory and field-based studies. Environ Toxicol Chem 2021;40:1639–1648. © 2021 SETAC

中文翻译：

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大西洋鳕鱼 (Gadus morhua) 肝脏暴露于有机磷阻燃剂后的肝脏基因表达谱揭示了胆固醇生物合成和脂质代谢的改变

自从逐步淘汰并最终禁止生产有机卤素阻燃剂以来，有机磷酸酯阻燃剂（OPFR）的使用量迅速增加。这导致在包括北极在内的各种环境中检测到 OPFR。在北极发现的两种最普遍的 OPFR 是磷酸三（2-氯异丙基）酯 (TCPP) 和磷酸 2-乙基己基二苯酯 (EHDPP)。人们对接触 OPFRs 对北极生物的影响知之甚少。本研究的目的是确定接触 TCPP、EHDPP 和 OPFR 混合物对大西洋鳕鱼（Gadus morhua ）基因表达模式的影响. 将来自大西洋鳕鱼的精确切割的肝切片在体外单独或混合暴露于 TCPP 或 EHDPP，并在 2 个不同的时间点取样，以使用 RNA 测序量化基因表达模式。我们将肝切片暴露于 2 种浓度的 TCPP 和 EHDPP，其中一种是根据北极环境中发现的水平选择的。RNA 测序结果表明数百个基因在暴露后的差异表达。代表胆固醇生物合成和脂质代谢途径的基因在所有治疗组中均显着富集。响应 OPFR 暴露，几乎所有胆固醇生物合成基因都显着下调。对这些途径的影响可能涉及各种生理过程，包括繁殖、生长、和行为以及对温度变化的适应。膜流动性是水生生物间重要的适应机制。通过改变水生生物对水温变化的适应潜力，尤其是生活在极地环境中的水温，胆固醇稳态的改变可能会产生长期后果。这些结果表明，与其他环境相比，OPFR 可能对生活在北极的生物产生独特的影响。需要进一步的研究，以通过实验室和实地研究来了解暴露于环境现实浓度的长期影响。通过改变水生生物对水温变化的适应潜力，尤其是生活在极地环境中的水温，胆固醇稳态的改变可能会产生长期后果。这些结果表明，与其他环境相比，OPFR 可能对生活在北极的生物产生独特的影响。需要进一步的研究，以通过实验室和实地研究来了解暴露于环境现实浓度的长期影响。通过改变水生生物对水温变化的适应潜力，尤其是生活在极地环境中的水温，胆固醇稳态的改变可能会产生长期后果。这些结果表明，与其他环境相比，OPFR 可能对生活在北极的生物产生独特的影响。需要进一步的研究，以通过实验室和实地研究来了解暴露于环境现实浓度的长期影响。环境毒物化学2021；40:1639–1648。© 2021 SETAC