A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i>
Thyroid hormones (TH) 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 TH signaling and the consequences on n...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2588 |
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| author | Michelle Leemans Petra Spirhanzlova Stephan Couderq Sébastien Le Mével Alexis Grimaldi Evelyne Duvernois-Berthet Barbara Demeneix Jean-Baptiste Fini |
| author_facet | Michelle Leemans Petra Spirhanzlova Stephan Couderq Sébastien Le Mével Alexis Grimaldi Evelyne Duvernois-Berthet Barbara Demeneix Jean-Baptiste Fini |
| author_sort | Michelle Leemans |
| collection | DOAJ |
| description | Thyroid hormones (TH) 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 TH 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. The potential consequences of EDC exposure on human health are far-reaching and include problems with immune function, reproductive health, and neurological development. We hypothesized that embryonic exposure to a mixture of chemicals (containing phenols, phthalates, pesticides, heavy metals, and perfluorinated, polychlorinated, and polybrominated compounds) identified as commonly found in the human amniotic fluid could lead to altered brain development. We assessed its effect on TH signaling and neurodevelopment in an amphibian model (<i>Xenopus laevis</i>) highly sensitive to thyroid disruption. Fertilized eggs were exposed for eight days to either TH (thyroxine, T<sub>4</sub> 10 nM) or the amniotic mixture (at the actual concentration) until reaching stage NF47, where we analyzed gene expression in the brains of exposed tadpoles using both RT-qPCR and RNA sequencing. The results indicate that whilst some overlap on TH-dependent genes exists, T<sub>4</sub> and the mixture have different gene signatures. Immunohistochemistry showed increased proliferation in the brains of T<sub>4</sub>-treated animals, whereas no difference was observed for the amniotic mixture. Further, we demonstrated diminished tadpoles’ motility in response to T<sub>4</sub> 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. |
| first_indexed | 2024-03-11T09:40:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:40:56Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7e3589b0b6bb430683bce177bdfa80af2023-11-16T16:59:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243258810.3390/ijms24032588A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i>Michelle Leemans0Petra Spirhanzlova1Stephan Couderq2Sébastien Le Mével3Alexis Grimaldi4Evelyne Duvernois-Berthet5Barbara Demeneix6Jean-Baptiste Fini7Département Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceDépartement Adaptations du Vivant (AVIV), Physiologie Moléculaire et Adaptation (PhyMA UMR 7221 CNRS), Muséum National d’Histoire Naturelle, CNRS, CP 32, 7 rue Cuvier, 75005 Paris, FranceThyroid hormones (TH) 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 TH 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. The potential consequences of EDC exposure on human health are far-reaching and include problems with immune function, reproductive health, and neurological development. We hypothesized that embryonic exposure to a mixture of chemicals (containing phenols, phthalates, pesticides, heavy metals, and perfluorinated, polychlorinated, and polybrominated compounds) identified as commonly found in the human amniotic fluid could lead to altered brain development. We assessed its effect on TH signaling and neurodevelopment in an amphibian model (<i>Xenopus laevis</i>) highly sensitive to thyroid disruption. Fertilized eggs were exposed for eight days to either TH (thyroxine, T<sub>4</sub> 10 nM) or the amniotic mixture (at the actual concentration) until reaching stage NF47, where we analyzed gene expression in the brains of exposed tadpoles using both RT-qPCR and RNA sequencing. The results indicate that whilst some overlap on TH-dependent genes exists, T<sub>4</sub> and the mixture have different gene signatures. Immunohistochemistry showed increased proliferation in the brains of T<sub>4</sub>-treated animals, whereas no difference was observed for the amniotic mixture. Further, we demonstrated diminished tadpoles’ motility in response to T<sub>4</sub> 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.https://www.mdpi.com/1422-0067/24/3/2588thyroid hormonesendocrine disruptionneurodevelopment<i>Xenopus laevis</i> |
| spellingShingle | Michelle Leemans Petra Spirhanzlova Stephan Couderq Sébastien Le Mével Alexis Grimaldi Evelyne Duvernois-Berthet Barbara Demeneix Jean-Baptiste Fini A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i> International Journal of Molecular Sciences thyroid hormones endocrine disruption neurodevelopment <i>Xenopus laevis</i> |
| title | A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i> |
| title_full | A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i> |
| title_fullStr | A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i> |
| title_full_unstemmed | A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i> |
| title_short | A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in <i>Xenopus laevis</i> |
| title_sort | mixture of chemicals found in human amniotic fluid disrupts brain gene expression and behavior in i xenopus laevis i |
| topic | thyroid hormones endocrine disruption neurodevelopment <i>Xenopus laevis</i> |
| url | https://www.mdpi.com/1422-0067/24/3/2588 |
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