Norwegian Polar Institute, Fram Centre, N-9296 Tromsø, Norway.
Norwegian Institute for Air Research, Fram Centre, N-9296 Tromsø, Norway.
Environ Int. 2021 Jul;152:106458. doi: 10.1016/j.envint.2021.106458. Epub 2021 Mar 4.
This study investigated concentrations of phthalates (diesters of phthalic acids) in blubber/adipose tissue of blue whales (Balaenoptera musculus), fin whales (Balaenoptera physalus), bowhead whales (Balaena mysticetus) and polar bears (Ursus maritimus) sampled in the Svalbard Archipelago (extending westward in the case of bowhead whales). Additionally, total concentrations (free and conjugated forms) of eight phthalate monoester metabolites were analysed in plasma of polar bears. Bis(2-ethylhexyl) phthalate (DEHP) was the only phthalate quantified among the 12 phthalates investigated. This compound was present in 6/7 fin whale samples, 4/7 blue whale samples, 2/5 bowhead whale samples and 1/12 polar bear samples. DEHP concentrations ranged from <20-398 ng/g wet weight. Phthalate metabolites, mono-n-butyl phthalate and monoisobutyl phthalate, were found in low concentrations (<1.2 ng/mL) in some of the polar bear samples. In vitro reporter gene assays were used to assess transcriptional activity of fin whale peroxisome proliferator-activated receptor gamma (PPARG), glucocorticoid receptor (GR) and the thyroid hormone receptor beta (THRB) by DEHP and diisononyl phthalate (DiNP). Due to the high degree of similarity of the ligand binding domain in the THRB and PPARG among whales, polar bears and humans, the transactivation results also apply for these species. DEHP showed both agonistic and antagonistic effects towards whale THRB at considerably higher concentrations than measured in the study animals; DiNP was a weak agonist of whale THRB. No significant agonistic or antagonistic effects were detected for DEHP or DiNP for whale PPARG, whereas DEHP and DiNP decreased basal luciferase activity mediated by whale GR at several test concentrations. In conclusion, DEHP was detected in the blubber of marine mammals from the Norwegian Arctic and it appears to have potential to modulate the transcriptional activity of whale THRB, but current DEHP concentrations do not modulate the function of the studied nuclear receptors in adipose tissue of blue whales, fin whales, bowhead whales or polar bears sampled from the Norwegian Arctic.
本研究调查了在斯瓦尔巴群岛（以弓头鲸为例向西延伸）采集的蓝鲸（Balaenoptera musculus）、长须鲸（Balaenoptera physalus）、北极露脊鲸（Balaena mysticetus）和北极熊（Ursus maritimus）的鲸脂/脂肪组织中邻苯二甲酸酯（邻苯二甲酸的二酯）的浓度。此外，还分析了北极熊血浆中 8 种邻苯二甲酸单酯代谢物的总浓度（游离和共轭形式）。在研究的 12 种邻苯二甲酸中，只有邻苯二甲酸二（2-乙基己基）酯（DEHP）被定量。该化合物存在于 6/7 份长须鲸样本、4/7 份蓝鲸样本、2/5 份弓头鲸样本和 1/12 份北极熊样本中。DEHP 浓度范围为<20-398ng/g 湿重。在一些北极熊样本中，发现邻苯二甲酸单丁酯和邻苯二甲酸单异丁酯等邻苯二甲酸代谢物的浓度较低（<1.2ng/mL）。体外报告基因试验用于评估 DEHP 和邻苯二甲酸二异壬酯（DiNP）对长须鲸过氧化物酶体增殖物激活受体γ（PPARG）、糖皮质激素受体（GR）和甲状腺激素受体β（THRB）的转录活性。由于鲸鱼、北极熊和人类的 THRB 和 PPARG 配体结合域高度相似，因此转激活结果也适用于这些物种。与研究动物中测量的浓度相比，DEHP 对鲸鱼 THRB 表现出激动剂和拮抗剂作用；DiNP 是鲸鱼 THRB 的弱激动剂。未检测到 DEHP 或 DiNP 对鲸鱼 PPARG 有明显的激动或拮抗作用，而 DEHP 和 DiNP 降低了几个测试浓度下由鲸鱼 GR 介导的基础荧光素酶活性。总之，在挪威北极的海洋哺乳动物的鲸脂中检测到了 DEHP，它似乎有潜力调节鲸鱼 THRB 的转录活性，但目前的 DEHP 浓度不会调节挪威北极采集的蓝鲸、长须鲸、弓头鲸或北极熊脂肪组织中研究核受体的功能。
