Huang Jin, Liu Kunyun, Chen Shan, Tang Huijia, Li Ruiwen, Wang Xianzheng, Sun Heying
Shengda Hydropower Co. Ltd, Power Construction Corporation of China, Leshan, China.
Monitoring Department One, Guizhou Provincial Ecological Environmental Monitoring Center, Guiyang, China.
J Appl Toxicol. 2025 Jun;45(6):916-924. doi: 10.1002/jat.4755. Epub 2025 Jan 28.
Fluoxetine (FLX), a typical selective serotonin reuptake inhibitors, has been frequently detected in aquatic environment and wild fish. However, little is known about its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 1, 3, 10, and 30 μg/L of FLX for 6 days. Chemical analysis demonstrated that FLX and its metabolic product (nonfluoxetine, NFLX) were accumulated in zebrafish larvae. The exposure resulted in decreased thyroid hormones (THs) levels, indicating thyroid endocrine disruption. Moreover, thyroid-stimulating hormone (TSH) content was significantly inhibited in a concentration-dependent manner after exposure to FLX. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (crh) and thyrotropin-releasing hormone (trh) were significantly up-regulated as a compensatory mechanism for the decreased TH contents accompanied with decreased tshβ mRNA expression. In addition, genes involved in thyroid hormone synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) and transport (transthyretin, ttr) were down-regulated after exposure to FLX in a concentration-dependent manner. The increased gene transcription of deiodinases (dio2) and uridinediphosphate-glucuronosyltransferase (ugt1ab) might be responsible for the decrease of TH contents. In addition, a significant inhibition in thyroid hormone receptors (trα and trβ) gene expression was observed upon treatment with FLX. All these results demonstrated that FLX could alter THs and TSH content as well as gene transcription in the HPT axis, exerting an endocrine disruption of the thyroid system in zebrafish larvae.
氟西汀（FLX）是一种典型的选择性5-羟色胺再摄取抑制剂，在水生环境和野生鱼类中经常被检测到。然而，关于其对甲状腺内分泌系统的影响却知之甚少。在本研究中，斑马鱼（Danio rerio）胚胎暴露于1、3、10和30μg/L的氟西汀中6天。化学分析表明，氟西汀及其代谢产物（去甲氟西汀，NFLX）在斑马鱼幼体中蓄积。暴露导致甲状腺激素（THs）水平降低，表明甲状腺内分泌受到干扰。此外，暴露于氟西汀后，促甲状腺激素（TSH）含量呈浓度依赖性显著抑制。进一步检测下丘脑-垂体-甲状腺（HPT）轴中的基因转录，结果显示，编码促肾上腺皮质激素释放激素（crh）和促甲状腺激素释放激素（trh）的基因显著上调，作为TH含量降低的一种补偿机制，同时tshβ mRNA表达降低。此外，暴露于氟西汀后，参与甲状腺激素合成（钠/碘同向转运体，nis，甲状腺球蛋白，tg）和转运（甲状腺素结合前白蛋白，ttr）的基因呈浓度依赖性下调。脱碘酶（dio2）和尿苷二磷酸葡萄糖醛酸转移酶（ugt1ab）基因转录增加可能是TH含量降低的原因。此外，用氟西汀处理后，观察到甲状腺激素受体（trα和trβ）基因表达受到显著抑制。所有这些结果表明，氟西汀可改变THs和TSH含量以及HPT轴中的基因转录，对斑马鱼幼体的甲状腺系统产生内分泌干扰。
