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Mixtures measured in human, disrupt thyroid hormone signaling and behavior in Xenopus laevis
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International audience. Endocrine disrupting chemicals (EDCs) harm human health both as singlemolecules and as mixtures. Most research on EDCs is done on individualchemicals whereas we are exposed to mixtures of numerous and possiblyinteracting molecules. This discrepancy presents a dilemma for risk assessmentand legislation. Thyroid hormones are essential for normal brain developmentwhere they influence, through specific embryonic and post-natal periods all thesteps of brain development. In adults, TH roles are essential to brain function andto general metabolism (thermogenesis, fat burning, etc.). As number ofcompounds produced by chemical industries increased by 300 fold since the70’s, and many reports in the scientific literature show that many of thesechemicals are potential Endocrine disruptors (EDCs) we questioned the thyroidhormone disrupting effect of common chemicals. We hypothesized that this axiscould be a key target for disruption and hence alter normal brain development. Totest this hypothesis, we used a thyroid disruptor screening assay, the XenopusEmbryonic Thyroid Assay (XETA), RT-qPCR on brain tissue, and behavioranalysis. We used to independent strategies with different mixtures from humandata. First we recreated m a mixture of 15 compounds commonly found in Humanbeings and tested them at the concentration meassured in amniotic fluid and studythe effects on thyroid hormone signaling and adverse effects on our tadpolemodel. Second, a novel approach, developed within the European project, EDCMixRisk, was to classify adverse mixtures of chemicals found in population basedon epidemiological studies and test their EDC potential with both in vivo andin vitro assays. Samples from about 2,000 pregnant women were examined andretrospective analysis on offspring identified a chemical mixture for whichembryonic exposure was associated with language delay, an indication forneurodevelopmental delay. Results on the two kind of mixtures show significantmodification of TH availability (XETA assay) at the actual mixture concentrationfound in fluids of pregnant women. Second, mRNA levels of key genes involvedthe TH-signaling pathway showed significant alteration of TH-dependent genes atthe accrual exposure level. Finally, mixtures were found to alter tadpoles’mobilitybehavior. Taken together, these results show advantages of using differentstrategies and necessity to take into consideration mixture in both experimentalstudies and risk assessment.
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