Abstract
Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.
Highlights
850 bp regulatory region of the TH/bZIP, a leucine zipper transcription factor highly sensitive to thyroid hormone regulation[13,14]
In this work we analysed the consequences of human amniotic fluid contaminant exposure during embryonic development on thyroid hormone signalling and brain development
Each chemical was screened in Xenopus embryonic thyroid assay (XETA) at least at three concentrations, both alone (Fig. S1a–g) and against a tri-iodothyronine (T3) challenge (5 × 10−9 M, Fig. 1)
Summary
850 bp regulatory region of the TH/bZIP, a leucine zipper transcription factor highly sensitive to thyroid hormone regulation[13,14]. Eleven of the 15 chemicals tested individually, exerted inhibitory or activating effects on thyroid hormone bioavailability in XETA. As synergistic effects of chemical mixtures without individual effects have been reported[10,15], we established a mixture of the 15 ubiquitous chemicals at concentrations reported in human amniotic fluids (Table S1). We used this mixture at three different concentrations, where 1x represents the concentrations of individual chemicals reported in human amniotic fluid. Effects of exposure were determined on thyroid hormone bioavailability (XETA), brain gene expression and structure, and behaviour. Significant and dose-dependent effects were found in all assays, raising the question of potential adverse effects of current chemical exposures on foetal brain development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
