Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae

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.