An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor
Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously...
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2025-06-01
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| author | Ikuko Miyazaki Chiharu Nishiyama Takeru Nagoshi Akane Miyako Suzuka Ono Ichika Misawa Aika Isse Kana Tomimoto Kaori Masai Kazumasa Zensho Masato Asanuma |
| author_facet | Ikuko Miyazaki Chiharu Nishiyama Takeru Nagoshi Akane Miyako Suzuka Ono Ichika Misawa Aika Isse Kana Tomimoto Kaori Masai Kazumasa Zensho Masato Asanuma |
| author_sort | Ikuko Miyazaki |
| collection | DOAJ |
| description | Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE·2H<sub>2</sub>O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE·2H<sub>2</sub>O (1–100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H<sub>2</sub>O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE·2H<sub>2</sub>O down-regulated <i>Hes1</i> expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE·2H<sub>2</sub>O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER. |
| format | Article |
| id | doaj-art-91ba6f944bef4e929e1269831f8897db |
| institution | Kabale University |
| issn | 2673-4087 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | NeuroSci |
| spelling | doaj-art-91ba6f944bef4e929e1269831f8897db2025-08-20T03:27:40ZengMDPI AGNeuroSci2673-40872025-06-01625310.3390/neurosci6020053An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen ReceptorIkuko Miyazaki0Chiharu Nishiyama1Takeru Nagoshi2Akane Miyako3Suzuka Ono4Ichika Misawa5Aika Isse6Kana Tomimoto7Kaori Masai8Kazumasa Zensho9Masato Asanuma10Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanBisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE·2H<sub>2</sub>O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE·2H<sub>2</sub>O (1–100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H<sub>2</sub>O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE·2H<sub>2</sub>O down-regulated <i>Hes1</i> expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE·2H<sub>2</sub>O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER.https://www.mdpi.com/2673-4087/6/2/53BADGEneurite outgrowthestrogen receptorGPERHes1neurogenin-3 |
| spellingShingle | Ikuko Miyazaki Chiharu Nishiyama Takeru Nagoshi Akane Miyako Suzuka Ono Ichika Misawa Aika Isse Kana Tomimoto Kaori Masai Kazumasa Zensho Masato Asanuma An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor NeuroSci BADGE neurite outgrowth estrogen receptor GPER Hes1 neurogenin-3 |
| title | An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor |
| title_full | An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor |
| title_fullStr | An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor |
| title_full_unstemmed | An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor |
| title_short | An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor |
| title_sort | endocrine disrupting chemical bisphenol a diglycidyl ether badge accelerates neuritogenesis and outgrowth of cortical neurons via the g protein coupled estrogen receptor |
| topic | BADGE neurite outgrowth estrogen receptor GPER Hes1 neurogenin-3 |
| url | https://www.mdpi.com/2673-4087/6/2/53 |
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