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XB-ART-53134
Sci Rep January 1, 2017; 7 43786.

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos.

Fini JB , Mughal BB , Le Mével S , Leemans M , Lettmann M , Spirhanzlova P , Affaticati P , Jenett A , Demeneix BA .


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.

PubMed ID: 28266608
PMC ID: PMC5339866
Article link: Sci Rep
Grant support: [+]
Genes referenced: bdnf ctrl dbp dio1 dio2 dio3 eef1a2 h3-3a ilf2 mbp ntsr1 odc1 pc.1 sox2 thibz thra thrb tubb2b


Article Images: [+] show captions
References [+] :
Abdelouahab, Maternal and cord-blood thyroid hormone levels and exposure to polybrominated diphenyl ethers and polychlorinated biphenyls during early pregnancy. 2013, Pubmed


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