Effects of an environmentally relevant PFAS mixture on dopamine and steroid hormone levels in exposed mice
Effects of an environmentally relevant PFAS mixture on dopamine and steroid hormone levels in exposed mice
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DOI：
10.1016/j.taap.2021.115670
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发表时间：
2021-08-19
影响因子：
3.8
通讯作者：
Arukwe, Augustine
中科院分区：
文献类型：
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作者：
Gronnestad, Randi;Johanson, Silje Modahl;Arukwe, Augustine
在本研究中，我们调查了多巴胺能和类固醇激素系统的A/J小鼠喂养环境相关浓度的全氟烷基物质（PFAS）的混合物在一段时间内的10周。PFAS混合物是根据挪威滑雪场（特隆赫姆）蚯蚓中测得的PFAS浓度选择的，由8种不同的PFAS组成。与对照组相比，饮食暴露于PFAS导致雄性小鼠脑内总多巴胺（DA）浓度降低。在转录水平上，PFAS暴露组雄性大鼠脑酪氨酸羟化酶（th）较对照组降低。负责DA代谢的酶，即单胺氧化酶（maoa和maob）和儿茶酚-O甲基转移酶（comt）的转录水平上没有显着差异。我们检测到PFAS暴露的女性中DA受体2（dr 2）的转录水平增加，而DA受体1（dr 1）、DA转运体（dat）和囊泡单胺转运体（vmat）的表达不受PFAS暴露的影响。关于类固醇激素，血浆和肌肉睾酮（T），11-酮睾酮（11-KT）和17 β-雌二醇（E2）水平，以及雌激素受体（esr 1和esr 2），促性腺激素释放激素（gnrh）和芳香化酶（cyp 19）的转录物未被PFAS处理改变。这些结果表明，暴露于PFAS剂量，相当于以前在挪威滑雪场的蚯蚓观察，可能会改变小鼠的多巴胺能系统的健康，一般生理，认知行为，生殖和代谢的明显后果。
In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely - monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17 beta-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.