Zhang Dan-Hua, Zhou En-Xiang, Yang Zhu-Lin
Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Research Laboratory of Hepatobiliary Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
PLoS One. 2017 May 3;12(5):e0176927. doi: 10.1371/journal.pone.0176927. eCollection 2017.
Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 μg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.
双酚S（BPS）作为一种工业原料被广泛使用，导致其在包括水环境在内的自然环境中广泛分布。然而，BPS对甲状腺内分泌系统的影响在很大程度上尚不清楚。在本研究中，斑马鱼（Danio rerio）胚胎在受精后2小时（hpf）至168 hpf期间暴露于1、3、10和30 μg/L的BPS中。检测了BPS的生物富集、全身甲状腺激素（THs）、促甲状腺激素（TSH）浓度以及与下丘脑-垂体-甲状腺（HPT）轴相关的关键基因的转录谱。化学分析表明BPS在斑马鱼幼体中蓄积。当BPS浓度分别≥10和30 μg/L时，甲状腺素（T4）和三碘甲状腺原氨酸（T3）水平显著降低。然而，在10和30 μg/L BPS处理组中TSH浓度显著升高。暴露于BPS后，当BPS浓度≥10 μg/L时，促肾上腺皮质激素释放激素（crh）和甲状腺球蛋白（tg）基因的mRNA表达以剂量反应方式上调。在30 μg/L BPS处理组中，参与甲状腺发育（pax8）和合成（钠/碘同向转运体，slc5a5）的基因转录也显著增加。此外，暴露于10 μg/L或更高浓度的BPS会显著上调与甲状腺激素代谢相关的基因（脱碘酶，dio1、dio2和尿苷二磷酸葡萄糖醛酸转移酶，ugt1ab），这可能是导致THs水平改变的原因。然而，当BPS浓度≥3 μg/L时，甲状腺素运载蛋白（ttr）的转录显著下调，而甲状腺激素受体（trα和trβ）和dio3的mRNA水平保持不变。所有结果表明，暴露于BPS会改变全身THs和TSH浓度，并改变与HPT轴相关的关键基因的表达谱，从而引发甲状腺内分泌紊乱。
