Liu Zidong, Tang Rong, Li Dapeng, Hu Qing, Wang Ying
College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, China.
Toxins (Basel). 2015 Jan 30;7(2):337-52. doi: 10.3390/toxins7020337.
Microcystin-LR (MC-LR) has been detected extensively in the aquatic environment and has the potential to disturb the thyroid endocrine system. However, limited information is available on the effects of subacute MC-LR exposure on fish thyroid hormone (TH) metabolism. In the present study, juvenile zebrafish (Danio rerio) were exposed to MC-LR at environmentally relevant concentrations (0, 1, 5, and 25 μg/L) for 28 days. Whole-body TH content and thyroid follicle histology were used as direct endpoints to assess thyroid disruption. The activities of iodothyronine deiodinases (IDs) and the transcription of selected genes associated with TH synthesis were also investigated to study the underlying mechanisms of endocrine disruption. Exposure of zebrafish to MC-LR significantly increased whole-body thyroxine (T4) content but decreased whole-body triiodothyronine (T3) content. We also observed hypertrophy and hyperplasia of the thyroid follicle epithelial cells, as well as up-regulation of corticotropin-releasing hormone (CRH), thyroid-stimulating hormone (TSH), thyroid peroxidase (TPO), and transthyretin (TTR) genes. The decreases in ID1 and ID2 activities coupled with an increase in ID3 activity were observed in MC-LR treatment groups. These results demonstrate that exposure to MC-LR at environmental concentrations results in the disturbance of TH homeostasis by disrupting the synthesis and conversion of THs.
微囊藻毒素-LR(MC-LR)已在水环境中被广泛检测到,并且有可能干扰甲状腺内分泌系统。然而,关于亚急性暴露于MC-LR对鱼类甲状腺激素(TH)代谢的影响,目前可用信息有限。在本研究中,将幼年斑马鱼(Danio rerio)暴露于环境相关浓度(0、1、5和25μg/L)的MC-LR中28天。以全身TH含量和甲状腺滤泡组织学作为评估甲状腺功能紊乱的直接指标。还研究了碘甲状腺原氨酸脱碘酶(IDs)的活性以及与TH合成相关的选定基因的转录,以探讨内分泌干扰的潜在机制。斑马鱼暴露于MC-LR后,全身甲状腺素(T4)含量显著增加,但全身三碘甲状腺原氨酸(T3)含量降低。我们还观察到甲状腺滤泡上皮细胞肥大和增生,以及促肾上腺皮质激素释放激素(CRH)、促甲状腺激素(TSH)、甲状腺过氧化物酶(TPO)和甲状腺素结合前白蛋白(TTR)基因的上调。在MC-LR处理组中观察到ID1和ID2活性降低,同时ID3活性增加。这些结果表明,在环境浓度下暴露于MC-LR会通过破坏TH的合成和转化而导致TH稳态紊乱。