{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:58:44Z","timestamp":1778947124715,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Okayama Medical Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>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\u00b72H2O), 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\u00b72H2O (1\u2013100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE\u00b72H2O 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\u00b72H2O down-regulated Hes1 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\u00b72H2O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER.<\/jats:p>","DOI":"10.3390\/neurosci6020053","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:08:31Z","timestamp":1749208111000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2732-094X","authenticated-orcid":false,"given":"Ikuko","family":"Miyazaki","sequence":"first","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9037-9159","authenticated-orcid":false,"given":"Chiharu","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeru","family":"Nagoshi","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akane","family":"Miyako","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzuka","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichika","family":"Misawa","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aika","family":"Isse","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Medical School, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Tomimoto","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0970-8104","authenticated-orcid":false,"given":"Kaori","family":"Masai","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-0725","authenticated-orcid":false,"given":"Kazumasa","family":"Zensho","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-7836","authenticated-orcid":false,"given":"Masato","family":"Asanuma","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1080\/02652030400007294","article-title":"Review of the toxicology, human exposure and safety assessment for bisphenol A diglycidylether (BADGE)","volume":"21","author":"Poole","year":"2004","journal-title":"Food Addit. 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