Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Front Endocrinol (Lausanne)
2022 Jan 01;13:995491. doi: 10.3389/fendo.2022.995491.
Show Gene links
Show Anatomy links
Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life.
Sousa-Vidal ÉK
,
Henrique G
,
da Silva REC
,
Serrano-Nascimento C
.
???displayArticle.abstract???
INTRODUCTION: DEHP is an endocrine disruptor widely used in the production of malleable plastics. DEHP exposure was associated with altered hypothalamic-pituitary-thyroid (HPT) axis function. Although previous studies reported deleterious effects of DEHP exposure during the intrauterine period, few studies have evaluated the direct effects triggered by this endocrine disruptor on the offspring animals' thyroid function. This study aimed to investigate the impact of intrauterine exposure to DEHP on the HPT axis function programming of the offspring animals during adulthood.
METHODS: Pregnant Wistar rats were orally treated with corn oil or corn oil supplemented with DEHP (0.48 or 4.8 mg/kg/day) throughout the gestational period. The offspring rats were euthanized on the 90th postnatal day. Hypothalamus, pituitary, thyroid, and liver were collected to analyze gene expression and protein content through qPCR and Western Blot. Blood was collected to determine TSH and thyroid hormone levels through fluorometric or chemiluminescence immunoassays.
RESULTS: In the adult F1 female rats, the highest dose of DEHP decreased TSH serum levels. In the thyroid, DEHP reduced the gene expression and/or protein content of NIS, TSHR, TG, TPO, MCT8, NKX2.1, PAX8, and FOXE1. These data are consistent with the reduction in T4 serum levels of the F1 DEHP-exposed female rats. In the liver, DEHP exposure increased the mRNA expression of Dio1 and Ttr, while the highest dose of DEHP reduced the mRNA expression of Ugt1a1 and Ugt1a6. Conversely, in the F1 male adult rats, TSHB expression and TSH serum levels were increased in DEHP-exposed animals. In the thyroid, except for the reduced protein content of TSHR, none of the evaluated genes/proteins were altered by DEHP. TH serum levels were not changed in the DEHP-exposed F1 male rats compared to the control group. Additionally, there were no significant alterations in the expression of hepatic enzymes in these animals.
DISCUSSION/CONCLUSIONS: Our results demonstrated, for the first time, that intrauterine exposure to DEHP disrupts the HPT axis function in male and female offspring rats and strongly suggest that DEHP exposure increases the susceptibility of the offspring animals to develop thyroid dysfunctions during adulthood.
Bergé,
Meta-analysis of environmental contamination by phthalates.
2013, Pubmed
Bergé,
Meta-analysis of environmental contamination by phthalates.
2013,
Pubmed
Bernal,
Thyroid hormone regulated genes in cerebral cortex development.
2017,
Pubmed
Bianco,
The Deiodinase Trio and Thyroid Hormone Signaling.
2018,
Pubmed
Bianco-Miotto,
Epigenetics and DOHaD: from basics to birth and beyond.
2017,
Pubmed
Blystone,
Determination of the di-(2-ethylhexyl) phthalate NOAEL for reproductive development in the rat: importance of the retention of extra animals to adulthood.
2010,
Pubmed
Chiamolera,
Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism.
2009,
Pubmed
Clark,
Modeling Human Exposure to Phthalate Esters: A Comparison of Indirect and Biomonitoring Estimation Methods.
2011,
Pubmed
Crobeddu,
Di(2-ethylhexyl) phthalate (DEHP) increases proliferation of epithelial breast cancer cells through progesterone receptor dysregulation.
2019,
Pubmed
Derakhshan,
Association of phthalate exposure with thyroid function during pregnancy.
2021,
Pubmed
Dickson-Spillmann,
Phthalate exposure through food and consumers' risk perception of chemicals in food.
2009,
Pubmed
Dong,
Effects of perinatal di (2-ethylhexyl) phthalate exposure on thyroid function in rat offspring.
2019,
Pubmed
Dong,
Effects of Long-Term In Vivo Exposure to Di-2-Ethylhexylphthalate on Thyroid Hormones and the TSH/TSHR Signaling Pathways in Wistar Rats.
2017,
Pubmed
Erkekoglu,
Genotoxicity of phthalates.
2014,
Pubmed
Fernández,
Thyroid transcription factors in development, differentiation and disease.
2015,
Pubmed
Gereben,
Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling.
2008,
Pubmed
Gluckman,
Effect of in utero and early-life conditions on adult health and disease.
2008,
Pubmed
Hocher,
More than genes: the advanced fetal programming hypothesis.
2014,
Pubmed
Hongjun,
Distribution of phthalate esters in topsoil: a case study in the Yellow River Delta, China.
2013,
Pubmed
Huang,
Changes in Urinary Phthalate Metabolite Levels Before and After the Phthalate Contamination Event and Identification of Exposure Sources in a Cohort of Taiwanese Children.
2017,
Pubmed
Huang,
Mediating role of oxidative/nitrosative stress biomarkers in the associations between phthalate exposure and thyroid function in Taiwanese adults.
2020,
Pubmed
Huang,
Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones.
2016,
Pubmed
Huang,
Characterization of phthalate exposure in relation to serum thyroid and growth hormones, and estimated daily intake levels in children exposed to phthalate-tainted products: A longitudinal cohort study.
2020,
Pubmed
Kambe,
Redox regulation of thyroid-transcription factors, Pax-8 and TTF-1, is involved in their increased DNA-binding activities by thyrotropin in rat thyroid FRTL-5 cells.
1996,
Pubmed
Kim,
Di-2-ethylhexylphthalate promotes thyroid cell proliferation and DNA damage through activating thyrotropin-receptor-mediated pathways in vitro and in vivo.
2019,
Pubmed
Kim,
DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption.
2021,
Pubmed
Liu,
DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats.
2015,
Pubmed
Lv,
Maternal exposure to bis(2-ethylhexyl) phthalate during the thyroid hormone-dependent stage induces persistent emotional and cognitive impairment in middle-aged offspring mice.
2022,
Pubmed
Lyche,
Reproductive and developmental toxicity of phthalates.
2009,
Pubmed
Mantzouratou,
Thyroid Hormone Signalling in Human Evolution and Disease: A Novel Hypothesis.
2021,
Pubmed
Martinez-Arguelles,
Fetal origin of endocrine dysfunction in the adult: the phthalate model.
2013,
Pubmed
Mullur,
Thyroid hormone regulation of metabolism.
2014,
Pubmed
Niermann,
Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice.
2015,
Pubmed
Okosieme,
Preconception management of thyroid dysfunction.
2018,
Pubmed
Patel,
Thyroid hormones and fetal neurological development.
2011,
Pubmed
Pierce,
Eli Lilly lecture. The subunits of pituitary thyrotropin--their relationship to other glycoprotein hormones.
1971,
Pubmed
Rowdhwal,
Toxic Effects of Di-2-ethylhexyl Phthalate: An Overview.
2018,
Pubmed
Sander,
Ponceau S waste: Ponceau S staining for total protein normalization.
2019,
Pubmed
Serrano,
Phthalates and diet: a review of the food monitoring and epidemiology data.
2014,
Pubmed
Serrano-Nascimento,
Evaluation of hypothalamus-pituitary-thyroid axis function by chronic perchlorate exposure in male rats.
2018,
Pubmed
Sherif,
The possible thyroid disruptive effect of di-(2-ethyl hexyl) phthalate and the potential protective role of selenium and curcumin nanoparticles: a toxicological and histological study.
2022,
Pubmed
Sun,
Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat.
2022,
Pubmed
Trnka,
Exposure to Di-2-ethylhexyl phthalate (DEHP) and infertility in women, NHANES 2013-2016.
2021,
Pubmed
Tsai,
Intake of Phthalate-tainted Foods and Serum Thyroid Hormones in Taiwanese Children and Adolescents.
2016,
Pubmed
Vassart,
The thyrotropin receptor and the regulation of thyrocyte function and growth.
1992,
Pubmed
Wu,
Novel insights into di‑(2‑ethylhexyl)phthalate activation: Implications for the hypothalamus‑pituitary‑thyroid axis.
2021,
Pubmed
Xu,
Di(2-ethylhexyl) phthalate induced thyroid toxicity via endoplasmic reticulum stress: In vivo and in vitro study.
2022,
Pubmed
Yao,
Maternal phthalate exposure during the first trimester and serum thyroid hormones in pregnant women and their newborns.
2016,
Pubmed
Ye,
Di2-ethylhexyl phthalate disrupts thyroid hormone homeostasis through activating the Ras/Akt/TRHr pathway and inducing hepatic enzymes.
2017,
Pubmed
Zhai,
Thyroid endocrine disruption in zebrafish larvae after exposure to mono-(2-ethylhexyl) phthalate (MEHP).
2014,
Pubmed
Zhang,
Transcriptomics and metabonomics analyses of maternal DEHP exposure on male offspring.
2018,
Pubmed
Zhang,
Roles and potential mechanisms of selenium in countering thyrotoxicity of DEHP.
2018,
Pubmed
Zhao,
The associations of urinary DEHP metabolite levels, serum thyroid hormones, and thyroid-related genes among the adolescent students from China: a cross-sectional study.
2022,
Pubmed
Zhao,
Prenatal di-(2-ethylhexyl) phthalate maternal exposure impairs the spatial memory of adult mouse offspring in a phase- and gender-dependent manner.
2020,
Pubmed
Zou,
Effect of di-(2-ethylhexyl) phthalate (DEHP) on allergic rhinitis.
2020,
Pubmed
Zuñiga,
Thyroid hormones: Metabolism and transportation in the fetoplacental unit.
2022,
Pubmed
van der Spek,
The classic pathways of thyroid hormone metabolism.
2017,
Pubmed