Leemans, M.; Spirhanzlova, P.; Couderq, S.; Le Mével, S.; Grimaldi, A.; Duvernois-Berthet, E.; Demeneix, B.; Fini, J.-B. A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in Xenopus laevis. Int. J. Mol. Sci.2023, 24, 2588.
Leemans, M.; Spirhanzlova, P.; Couderq, S.; Le Mével, S.; Grimaldi, A.; Duvernois-Berthet, E.; Demeneix, B.; Fini, J.-B. A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in Xenopus laevis. Int. J. Mol. Sci. 2023, 24, 2588.
Leemans, M.; Spirhanzlova, P.; Couderq, S.; Le Mével, S.; Grimaldi, A.; Duvernois-Berthet, E.; Demeneix, B.; Fini, J.-B. A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in Xenopus laevis. Int. J. Mol. Sci.2023, 24, 2588.
Leemans, M.; Spirhanzlova, P.; Couderq, S.; Le Mével, S.; Grimaldi, A.; Duvernois-Berthet, E.; Demeneix, B.; Fini, J.-B. A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in Xenopus laevis. Int. J. Mol. Sci. 2023, 24, 2588.
Abstract
Thyroid hormones (THs) are essential for normal brain development, influencing neural cell differentiation, migration, and synaptogenesis. Multiple endocrine-disrupting chemicals (EDCs) are found in the environment, raising concern for their potential effects on thyroid hormone signaling and the consequences on neurodevelopment and behavior. While most research on EDCs investigates the effects of individual chemicals, human health may be adversely affected by a mixture of chemicals. Many compounds belonging to a wide range of chemical classes have been identified as EDCs, notably those affecting thyroid hormone signaling. We hypothesized that embryonic exposure to a mixture of chemicals (containing phenols, phthalates, pesticides, heavy metals, perfluorinated -, polychlorinated, and polybrominated compound) commonly found in the human amniotic fluid could lead to altered brain development to assess its effect on thyroid hormone signaling and neurodevelopment in an amphibian model (Xenopus laevis), highly sensitive to thyroid disruption. Newly hatched tadpoles were exposed for eight days to either TH (thyroxine, T4 10nM) or the amniotic mixture (1x concentration) and gene expression was analyzed in the brains of exposed tadpoles using both RT-qPCR and RNA sequencing. Results indicate that whilst some overlap on TH-dependent genes exist, T4 and the mixture have different gene signatures. Immunohistochemistry showed increased proliferation in the brains of T4-treated animals whereas no difference was observed for the amniotic mixture. Further, we demonstrated diminished tadpoles’ motility in response to T4 and mixture exposure. As the individual chemicals composing the mixture are considered safe, these results highlight the importance of examining the effects of mixtures to improve risk assessment
Keywords
Thyroid hormones; Mixture; Neurodevelopment; Xenopus laevis; EDC
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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