Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain
Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been p...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/13121 |
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| author | Agnieszka Wnuk Joanna Rzemieniec Karolina Przepiórska Bernadeta Angelika Pietrzak Marzena Maćkowiak Małgorzata Kajta |
| author_facet | Agnieszka Wnuk Joanna Rzemieniec Karolina Przepiórska Bernadeta Angelika Pietrzak Marzena Maćkowiak Małgorzata Kajta |
| author_sort | Agnieszka Wnuk |
| collection | DOAJ |
| description | Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the <i>Esr1</i> gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of <i>Esr2</i>, <i>Gper1</i>, <i>Ahr</i>, <i>Arnt</i>, <i>Cyp19a1</i>, <i>Cyp1a1</i>, and <i>Atg7</i>, and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes. |
| first_indexed | 2024-03-10T04:52:44Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:44Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d21e9316cbcd499faad2f1873a37561b2023-11-23T02:33:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122231312110.3390/ijms222313121Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse BrainAgnieszka Wnuk0Joanna Rzemieniec1Karolina Przepiórska2Bernadeta Angelika Pietrzak3Marzena Maćkowiak4Małgorzata Kajta5Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, PolandLaboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, PolandTriclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the <i>Esr1</i> gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of <i>Esr2</i>, <i>Gper1</i>, <i>Ahr</i>, <i>Arnt</i>, <i>Cyp19a1</i>, <i>Cyp1a1</i>, and <i>Atg7</i>, and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes.https://www.mdpi.com/1422-0067/22/23/13121DNA methylationenvironmentally pervasive chemicalsestrogen receptorsmicroarraysxenobiotic receptors |
| spellingShingle | Agnieszka Wnuk Joanna Rzemieniec Karolina Przepiórska Bernadeta Angelika Pietrzak Marzena Maćkowiak Małgorzata Kajta Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain International Journal of Molecular Sciences DNA methylation environmentally pervasive chemicals estrogen receptors microarrays xenobiotic receptors |
| title | Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain |
| title_full | Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain |
| title_fullStr | Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain |
| title_full_unstemmed | Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain |
| title_short | Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain |
| title_sort | prenatal exposure to triclocarban impairs esr1 signaling and disrupts epigenetic status in sex specific ways as well as dysregulates the expression of neurogenesis and neurotransmitter related genes in the postnatal mouse brain |
| topic | DNA methylation environmentally pervasive chemicals estrogen receptors microarrays xenobiotic receptors |
| url | https://www.mdpi.com/1422-0067/22/23/13121 |
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