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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
A System Biology Approach Reveals New Targets for Human Thyroid Gland Toxicity in Embryos and Adult Individuals
Jeane Maria Oliveira1, Jamilli Zenzeluk1, Caroline Serrano-Nascimento2,3
1Department of Medicine, Laboratory of Reproductive Toxicology, State University of the Midwest (UNICENTRO), Alameda Élio Antonio Dalla Vecchia, nº 838, Guarapuava 85040-167, PR, Brazil.
Abstract:
Compounds of natural or synthetic origin present in personal care products, food additives, and packaging may interfere with hormonal regulation and are called endocrine-disrupting chemicals (EDCs). The thyroid gland is an important target of these compounds. The objective of this study was to analyze public data on the human thyroid transcriptome and investigate potential new targets of EDCs in the embryonic and adult thyroid glands. We compared the public transcriptome data of adult and embryonic human thyroid glands and selected 100 up- or downregulated genes that were subsequently subjected to functional enrichment analysis. In the embryonic thyroid, the most highly expressed gene was PRMT6, which methylates arginine-4 of histone H2A (86.21%), and the downregulated clusters included plasma lipoprotein particles (39.24%) and endopeptidase inhibitory activity (24.05%). For the adult thyroid gland, the most highly expressed genes were related to the following categories: metallothionein-binding metals (56.67%), steroid hormone biosynthetic process (16.67%), and cellular response to vascular endothelial growth factor stimulus (6.67%). Several compounds ranging from antihypertensive drugs to enzyme inhibitors were identified as potentially harmful to thyroid gland development and adult function.
Insights
Endocrine-disrupting chemicals (EDCs) can harm thyroid gland function. This study analyzed human thyroid transcriptomes to identify new EDC targets in both embryonic and adult thyroids, revealing potential risks from various compounds.
Area of Science:
- Endocrinology
- Toxicology
- Genomics
Background:
- Endocrine-disrupting chemicals (EDCs) are compounds that interfere with hormonal regulation.
- The thyroid gland is a significant target for EDC toxicity.
- Understanding EDC impacts on the thyroid is crucial for public health.
Purpose of the Study:
- To identify novel human thyroid targets of endocrine-disrupting chemicals (EDCs).
- To compare the transcriptome of embryonic and adult human thyroid glands in relation to potential EDC exposure.
- To investigate the functional impact of EDCs on thyroid development and function.
Main Methods:
- Analysis of public human thyroid transcriptome data from embryonic and adult samples.
- Identification and selection of 100 up- or downregulated genes.
- Functional enrichment analysis of selected genes.
Main Results:
- In embryonic thyroids, PRMT6 was highly expressed, while downregulated clusters involved lipoprotein particles and endopeptidase inhibition.
- In adult thyroids, highly expressed genes related to metallothionein-binding metals, steroid hormone biosynthesis, and growth factor response.
- Several compounds, including drugs and inhibitors, were implicated as potentially harmful to thyroid function.
Conclusions:
- Transcriptome analysis reveals distinct gene expression patterns in embryonic and adult thyroids.
- EDCs may target specific molecular pathways in the developing and adult thyroid gland.
- Further research is warranted to elucidate the mechanisms of EDC-induced thyroid dysfunction.
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