As a feed additive in agriculture, the antibiotic oxytetracycline (OTC) has become widely distributed in the natural environment, leading to the exposure of many organisms to low doses of OTC. Although OTC is clinically contraindicated in children because of its multiple side effects, the effect of exposure to low doses of environmental OTC on children is unknown, particularly during development. In this study, we investigated the effects of OTC on the thyroid endocrine system in zebrafish, through determinations of the whole-body contents of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) by enzyme-linked immunosorbent assay, and analysis of the mRNA expression of regulatory genes involved in the hypothalamus–pituitary–thyroid (HPT) axis using quantitative real-time polymerase chain reaction. Zebrafish embryos were exposed to OTC at environmentally relevant concentrations from 2 h to 120 days post-fertilisation. After exposure to OTC at 1,000 and 5,000 ng/L, T3 contents were significantly enhanced (37.8% and 45.1%, respectively) and TSH contents were reduced (16% and 16.3%, respectively) compared with those in the controls. The OTC-driven increase in the transcription of genes involved in thyroid synthesis (tpo and nis) may be responsible for the altered T3 levels. These data indicate that OTC may cause thyroid dysfunction and lead to reduced TSH secretion owing to enhanced negative feedback control of the HPT axis. Meanwhile, a decrease in body length, weight, and BMI and an increase in heart rate were observed with increasing OTC exposure. In conclusion, our results indicate that long-term exposure to low concentrations of OTC may alter the transcription of key genes involved in the HPT axis, as well as T3 and TSH contents, thereby disrupting the thyroid system and affecting the growth and development of zebrafish.

作为农业的饲料添加剂，抗生素土霉素已广泛分布于自然环境中，导致许多生物暴露于低剂量的OTC中。尽管OTC在儿童中由于其多种副作用在临床上是禁忌的，但未知暴露于小剂量环境OTC对儿童的影响，尤其是在发育过程中。在这项研究中，我们通过酶联免疫吸附剂测定三碘甲状腺素（T3），甲状腺素（T4）和促甲状腺激素（TSH）的体内含量，研究了OTC对斑马鱼甲状腺内分泌系统的影响定量实时聚合酶链反应检测和分析下丘脑-垂体-甲状腺（HPT）轴相关调控基因的mRNA表达。受精后2小时至120天，将斑马鱼胚胎以与环境相关的浓度暴露于OTC。与对照组相比，在以1,000和5,000 ng / L的OTC暴露后，T3含量显着提高（分别为37.8％和45.1％），TSH含量降低（分别为16％和16.3％）。OTC驱动的甲状腺合成相关基因转录的增加（tpo和nis）可能是导致T3水平改变的原因。这些数据表明，由于增强了对HPT轴的负反馈控制，OTC可能会导致甲状腺功能障碍并导致TSH分泌减少。同时，随着OTC暴露量的增加，体重，体重和BMI减少，心率增加。总之，我们的结果表明，长期暴露于低浓度的OTC可能会改变HPT轴中涉及的关键基因的转录以及T3和TSH含量，从而破坏甲状腺系统并影响斑马鱼的生长发育。