Guilherme Henrique, Érica Kássia Sousa-Vidal, Renata Elen Costa Da Silva, Nuha Ahmad Dsouki, Gisele Giannocco, Caroline Serrano-Nascimento
{"title":"Intrauterine triclosan exposure disrupts hypothalamus-pituitary-thyroid axis function in offspring rats.","authors":"Guilherme Henrique, Érica Kássia Sousa-Vidal, Renata Elen Costa Da Silva, Nuha Ahmad Dsouki, Gisele Giannocco, Caroline Serrano-Nascimento","doi":"10.1530/JOE-25-0069","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1530/JOE-25-0069","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"Print","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.