Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20100 Milan, Italy.
Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy.
Int J Mol Sci. 2022 May 23;23(10):5833. doi: 10.3390/ijms23105833.
Benzo(a)Pyrene (BaP) is one of the most widespread polycyclic aromatic hydrocarbons (PAHs) with endocrine disrupting properties and carcinogenic effects. In the present study, we tested the effect of BaP on thyroid development and function, using zebrafish as a model system. Zebrafish embryos were treated with 50 nM BaP from 2.5 to 72 h post fertilization (hpf) and compared to 1.2% DMSO controls. The expression profiles of markers of thyroid primordium specification, thyroid hormone (TH) synthesis, hypothalamus-pituitary-thyroid (HPT) axis, TH transport and metabolism, and TH action were analyzed in pools of treated and control embryos at different developmental stages. BaP treatment did not affect early markers of thyroid differentiation but resulted in a significant decrease of markers of TH synthesis ( and ) likely secondary to defective expression of the central stimulatory hormones of thyroid axis (, ) and of TH metabolism (). Consequently, immunofluorescence of BaP treated larvae showed a low number of follicles immunoreactive to T4. In conclusion, our results revealed that the short-term exposure to BaP significantly affects thyroid function in zebrafish, but the primary toxic effects would be exerted at the hypothalamic-pituitary level thus creating a model of central hypothyroidism.
苯并(a)芘(BaP)是一种分布广泛的多环芳烃(PAHs),具有内分泌干扰特性和致癌作用。在本研究中,我们使用斑马鱼作为模型系统,测试了 BaP 对甲状腺发育和功能的影响。将斑马鱼胚胎从受精后 2.5 至 72 小时(hpf)用 50 nM BaP 处理,并与 1.2% DMSO 对照组进行比较。在不同发育阶段,对处理和对照胚胎的混合物中甲状腺原基特化、甲状腺激素(TH)合成、下丘脑-垂体-甲状腺(HPT)轴、TH 转运和代谢以及 TH 作用的标志物表达谱进行了分析。BaP 处理不会影响甲状腺分化的早期标志物,但会导致 TH 合成标志物(和)显著降低,可能是甲状腺轴的中枢刺激激素(、)和 TH 代谢()表达缺陷所致。因此,BaP 处理的幼虫的免疫荧光显示对 T4 反应的滤泡数量减少。总之,我们的研究结果表明,短期暴露于 BaP 会显著影响斑马鱼的甲状腺功能,但主要的毒性作用可能发生在下丘脑-垂体水平,从而建立一种中枢性甲状腺功能减退症的模型。