An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor.

IF 1.6 Q3 CLINICAL NEUROLOGY
NeuroSci Pub Date : 2025-06-06 DOI:10.3390/neurosci6020053
Ikuko Miyazaki, Chiharu Nishiyama, Takeru Nagoshi, Akane Miyako, Suzuka Ono, Ichika Misawa, Aika Isse, Kana Tomimoto, Kaori Masai, Kazumasa Zensho, Masato Asanuma
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Abstract

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·2H2O), 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·2H2O (1-100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H2O 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·2H2O 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·2H2O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER.

一种内分泌干扰化学物质,双酚A二甘油酯(BADGE),通过g蛋白偶联雌激素受体加速神经细胞的发生和皮质神经元的生长。
双酚A二缩水甘油酯醚(BADGE)是环氧树脂的主要成分,用于罐头食品和塑料食品容器的内涂。BADGE很容易从容器中迁移,导致食品污染;这种化合物被称为干扰内分泌的化学物质。我们之前报道,母体在妊娠期和哺乳期暴露于双酚A双(2,3-二羟丙基)醚(BADGE·2H2O)可加速胎儿皮质神经元分化并诱导幼年小鼠焦虑样行为。双酚A双(2,3-二羟丙基)醚是不仅在罐头食品中而且在人体标本中检测最多的BADGE衍生物。在本研究中,我们研究了低剂量BADGE·2H2O (1-100 pM)处理对皮层神经元神经突的影响以及神经突生长的机制。BADGE·2H2O暴露显著增加皮质神经元树突数量和神经突长度;雌激素受体(ER)拮抗剂ICI 182780和g蛋白偶联雌激素受体(GPER)拮抗剂G15可抑制这些加速作用。BADGE·2H2O下调Hes1转录抑制因子的表达,增加皮层神经元中神经生成因子神经原素-3 (Ngn3)的水平;这些变化被G15显著阻断。这些数据表明,直接暴露于BADGE·2H2O可以通过下调Hes1和通过内质网(尤其是GPER)增加Ngn3水平来加速皮质神经元的神经发生和生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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