Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine-Disrupting Chemicals on Child Neurodevelopment

Thyroid hormones are crucial in normal brain development. Transient and mild thyroid hormone insufficiency in pregnancy is also associated with impaired neurodevelopment in the offspring (e.g., 3-4 IQ score loss in association with maternal free thyroxine in the lowest fifth percentile). While inade...

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Published in:Frontiers in endocrinology (Lausanne) Vol. 9; p. 204
Main Authors: Ghassabian, Akhgar, Trasande, Leonardo
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 30.04.2018
Subjects:
brain
children
endocrine disrupting chemicals
Endocrinology
neurodevelopment
thyroid
neurodevelopment
thyroid
brain
children
endocrine disrupting chemicals
ISSN:1664-2392, 1664-2392
Online Access:Get full text
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Summary:Thyroid hormones are crucial in normal brain development. Transient and mild thyroid hormone insufficiency in pregnancy is also associated with impaired neurodevelopment in the offspring (e.g., 3-4 IQ score loss in association with maternal free thyroxine in the lowest fifth percentile). While inadequate iodine intake remains the most common underlying cause of mild thyroid hormone insufficiency in vulnerable populations including pregnant women, other factors such as exposure to environmental contaminants have recently attracted increasing attention, in particular in interaction with iodine deficiency. Endocrine-disrupting chemicals (EDCs) are natural and synthetic substances with ubiquitous exposure in children and adults including pregnant women. EDCs interfere, temporarily or permanently, with hormonal signaling pathways in the endocrine system by binding to hormone receptors and modifying gene expression. Other mechanisms involve alterations in production, metabolism, and transfer of hormones. Experimental studies have shown that exposures to EDCs affect various brain processes such as neurogenesis, neural differentiation and migration, as well as neural connectivity. Neuroimaging studies confirm brain morphological abnormalities (e.g., cortical thinning) consistent with neurodevelopmental impairments as a result of EDC exposures at standard use levels. In this review, we provide an overview of present findings from toxicological and human studies on the anti-thyroid effect of EDCs with a specific attention to fetal and early childhood exposure. This brief overview highlights the need for additional multidisciplinary studies with a focus on thyroid disruption as an underlying mechanism for developmental neurotoxicity of EDC, which can provide insight into modifiable risk factors of developmental delays in children.
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Edited by: Tim I. M. Korevaar, Erasmus University Rotterdam, Netherlands
Reviewed by: Barbara Anne Demeneix, Centre national de la recherche scientifique (CNRS), France; Laurent M. Sachs, Muséum national d’Histoire naturelle, France; Salvatore Benvenga, Università degli Studi di Messina, Italy
Specialty section: This article was submitted to Thyroid Endocrinology, a section of the journal Frontiers in Endocrinology
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2018.00204