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吡丙醚对斑马鱼下丘脑-垂体-甲状腺(HPT)轴的影响。

Effects of penthiopyrad on the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish.

机构信息

College of Horticulture and plant protection, Henan University of Science and Technology, Luoyang, Henan Province, People's Republic of China.

College of Horticulture and plant protection, Henan University of Science and Technology, Luoyang, Henan Province, People's Republic of China.

出版信息

Pestic Biochem Physiol. 2024 Jun;202:105961. doi: 10.1016/j.pestbp.2024.105961. Epub 2024 May 15.

DOI:10.1016/j.pestbp.2024.105961
PMID:38879309
Abstract

Exposure to specific pesticides has been demonstrated to alter normal thyroid function of aquatic vertebrates. This study aimed to investigate the impact of penthiopyrad (PO) on the thyroid function of zebrafish, further elucidating its toxic mechanisms on the early developmental stages of zebrafish. Exposure to sublethal doses of PO (0.3-1.2 mg/L) for 8 days from 2 h after fertilization resulted in a significant reduction in larval swim bladder size and body weight, accompanied by developmental abnormalities such as pigment deposition and abnormal abdominal development. Perturbations in the hypothalamic-pituitary-thyroid (HPT) axis in larvae manifested as a marked upregulation of crh, tg, ttr, and ugt1ab expression, alongside downregulation of trβ expression, culminating in elevated thyroxine (T4) and triiodothyronine (T3) levels. Additionally, molecular docking results suggest that PO and its metabolites may disrupt the binding of thyroid hormones to thyroid hormone receptor beta (TRβ), compromising the normal physiological function of TRβ. These findings highlight the PO-induced adverse effects on the HPT axis of larvae under sublethal doses, eventually leading to abnormal development and growth inhibition.

摘要

暴露于特定的杀虫剂已被证明会改变水生脊椎动物的正常甲状腺功能。本研究旨在探讨吡丙醚(PO)对斑马鱼甲状腺功能的影响,进一步阐明其对斑马鱼早期发育阶段的毒性机制。从受精后 2 小时开始,暴露于亚致死剂量的 PO(0.3-1.2mg/L)8 天,导致幼鱼鳔大小和体重显著减小,同时伴有色素沉着和腹部发育异常等发育异常。幼鱼下丘脑-垂体-甲状腺(HPT)轴的紊乱表现为 crh、tg、ttr 和 ugt1ab 表达的显著上调,同时 trβ 表达下调,导致甲状腺素(T4)和三碘甲状腺原氨酸(T3)水平升高。此外,分子对接结果表明,PO 和其代谢物可能会破坏甲状腺激素与甲状腺激素受体β(TRβ)的结合,从而损害 TRβ 的正常生理功能。这些发现强调了 PO 在亚致死剂量下对幼虫 HPT 轴的不良影响,最终导致发育异常和生长抑制。

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