title: Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos.
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.
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Fini
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Bilal B
authors.initials: BB
authors.lastname: Mughal
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Le Mével
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Leemans
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Mélodie
authors.initials: M
authors.lastname: Lettmann
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Petra
authors.initials: P
authors.lastname: Spirhanzlova
authors.affiliation: UMR CNRS TEFOR, Tefor Core Facility Paris-Saclay Institute of Neuroscience UMR 9197, CNRS, Université Paris-Saclay, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Affaticati
authors.affiliation: UMR CNRS TEFOR, Tefor Core Facility Paris-Saclay Institute of Neuroscience UMR 9197, CNRS, Université Paris-Saclay, France.
authors.forename: Arnim
authors.initials: A
authors.lastname: Jenett
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Sorbonne Université, 75231 Paris, France.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Demeneix
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D052244:Endocrine Disruptors; D013963:Thyroid Hormones