宫内暴露三氯生破坏子代大鼠下丘脑-垂体-甲状腺轴功能。

IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Journal of Endocrinology Pub Date : 2025-09-18 Print Date: 2025-09-01 DOI:10.1530/JOE-25-0069
Guilherme Henrique, Érica Kássia Sousa-Vidal, Renata Elen Costa Da Silva, Nuha Ahmad Dsouki, Gisele Giannocco, Caroline Serrano-Nascimento
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引用次数: 0

摘要

三氯生(TCS)是一种广泛用于个人护理产品的抗菌剂,与甲状腺功能受损和甲状腺激素(TH)水平降低有关。然而,其在甲状腺功能障碍发育过程中的潜在作用尚不清楚。本研究探讨了宫内TCS暴露对成年大鼠子代下丘脑-垂体-甲状腺(HPT)轴的长期影响。妊娠Wistar大鼠在妊娠期间口服玉米油(对照)或TCS(10或30 mg/kg/天)。在产后90天(PND90)对子代大鼠实施安乐死,收集下丘脑、垂体、甲状腺、肝脏和血清组织进行分析。RT-qPCR和Western blotting检测基因和蛋白表达;形态学评估甲状腺组织学;ELISA法检测全基因组DNA甲基化;免疫法测定血清TSH和THs。TCS暴露改变下丘脑TRH含量,降低垂体Gh mRNA表达,降低血清TSH水平。在甲状腺中,Slc5a5、Tg、Tpo、Tshr、Pax8、Nkx2.1下调,同时伴有NIS、Tpo蛋白表达降低,循环T4水平降低。组织学分析显示两性的卵泡直径减小。表观遗传变化包括两性总体DNA甲基化和H3组蛋白甲基化增加,以及男性H3乙酰化减少。此外,TCS暴露改变了参与TH代谢的肝酶,表明全身内分泌紊乱。总的来说,这些发现表明宫内TCS暴露增加了成年期甲状腺功能减退的易感性,突出了其作为发育性甲状腺干扰物的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intrauterine triclosan exposure disrupts hypothalamus-pituitary-thyroid axis function in offspring rats.

Triclosan (TCS), an antimicrobial agent widely used in personal care products, has been associated with impaired thyroid function and reduced thyroid hormone (TH) levels. However, its potential role in the developmental programming of thyroid dysfunction remains unclear. This study investigated the long-term effects of intrauterine TCS exposure on the hypothalamic-pituitary-thyroid (HPT) axis in adult rat offspring. Pregnant Wistar rats received oral doses of corn oil (control) or TCS (10 or 30 mg/kg/day) throughout gestation. Offspring rats were euthanized on postnatal day 90 (PND90), and tissues from the hypothalamus, pituitary, thyroid, liver, and serum were collected for analysis. Gene and protein expression were evaluated by RT-qPCR and Western blotting; thyroid histology was assessed morphologically; global DNA methylation was measured by ELISA; and serum TSH and THs were quantified through immunoassays. TCS exposure altered hypothalamic TRH content, reduced Gh mRNA expression in the pituitary, and decreased serum TSH levels. In the thyroid, Slc5a5, Tg, Tpo, Tshr, Pax8, and Nkx2.1 were downregulated, accompanied by reduced NIS and TPO protein expression and decreased circulating T4 levels. Histological analyses revealed reduced follicular diameter in both sexes. Epigenetic changes included increased global DNA methylation and H3 histone methylation in both sexes, along with reduced H3 acetylation in males. In addition, TCS exposure altered hepatic enzymes involved in TH metabolism, indicating systemic endocrine disruption. Collectively, these findings demonstrate that intrauterine TCS exposure increases susceptibility to thyroid hypofunction in adulthood, highlighting its potential role as a developmental thyroid disruptor.

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来源期刊
Journal of Endocrinology
Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.50%
发文量
113
审稿时长
4-8 weeks
期刊介绍: Journal of Endocrinology is a leading global journal that publishes original research articles, reviews and science guidelines. Its focus is on endocrine physiology and metabolism, including hormone secretion; hormone action; biological effects. The journal publishes basic and translational studies at the organ, tissue and whole organism level.
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