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低剂量双酚A会干扰人类神经干细胞/祖细胞的神经元分化。

Low Doses of Bisphenol A Disrupt Neuronal Differentiation of Human Neuronal Stem/Progenitor Cells.

作者信息

Kiso-Farnè Kaori, Yaoi Takeshi, Fujimoto Takahiro, Itoh Kyoko

机构信息

Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

出版信息

Acta Histochem Cytochem. 2022 Dec 28;55(6):193-202. doi: 10.1267/ahc.22-00090. Epub 2022 Dec 20.

DOI:10.1267/ahc.22-00090
PMID:36688137
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9840471/
Abstract

Bisphenol A (BPA) is an endocrine disrupting chemical. Human epidemiological studies have suggested that adverse neurobehavioral outcomes are induced by fetal exposure to BPA. The remarkable differences in the corticogenesis between human and agyrencephalic mammals are an increase in the intermediate progenitor cells (IPCs) and a following increase in the subplate thickness. It is uncertain whether low doses of BPA (low-BPA) affect human early corticogenesis when basal progenitor cells (BPs) produce IPCs resulting in amplified neurogenesis. In this study, human-derived neuronal stem/progenitor cells were exposed to low-BPA or the vehicle only, and the resultant cell type-specific molecular changes and morphology were analyzed. We focused on stem cells immunoreactive for SOX2, BPs for NHLH1, and immature neurons for DCX. SOX2-positive cells significantly decreased at day (DIV) 4 and 7, whereas NHLH1-positive cells tended to be higher, while DCX-positive cells significantly increased at DIV7 when exposed to 100 nM of BPA compared with the vehicle. Morphologically DCX-positive cells showed a decrease in unipolar cells and an increase in multipolar cells when exposed to 100 nM of BPA compared with the vehicle. These results provide insights into the effect of low-BPA on neuronal differentiation in the human fetal corticogenesis.

摘要

双酚A（BPA）是一种内分泌干扰化学物质。人类流行病学研究表明，胎儿暴露于BPA会导致不良的神经行为后果。人类与无脑回哺乳动物在皮质发生过程中的显著差异在于中间祖细胞（IPC）数量增加以及随后的板下层厚度增加。当基础祖细胞（BP）产生IPC从而导致神经发生扩增时，低剂量的BPA（低BPA）是否会影响人类早期皮质发生尚不确定。在本研究中，将人源神经干细胞/祖细胞暴露于低BPA或仅溶剂中，并分析由此产生的细胞类型特异性分子变化和形态。我们重点关注SOX2免疫反应阳性的干细胞、NHLH1阳性的BP以及DCX阳性的未成熟神经元。与溶剂相比，当暴露于100 nM BPA时，SOX2阳性细胞在第4天和第7天显著减少，而NHLH1阳性细胞趋于增多，而DCX阳性细胞在第7天显著增加。在形态上，与溶剂相比，当暴露于100 nM BPA时，DCX阳性细胞的单极细胞减少，多极细胞增加。这些结果为低BPA对人类胎儿皮质发生中神经元分化的影响提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/9e78b4e1f5e2/AHC22-00090f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/caedf9ffc31e/AHC22-00090f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/58dc3080e8f3/AHC22-00090f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/8388389e6f2b/AHC22-00090f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/f03340810f4d/AHC22-00090f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/71a0afeaab5c/AHC22-00090f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/20313651eca9/AHC22-00090f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/76f0043adc60/AHC22-00090f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/e99dbcf324ac/AHC22-00090f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/9e78b4e1f5e2/AHC22-00090f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/caedf9ffc31e/AHC22-00090f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/58dc3080e8f3/AHC22-00090f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/8388389e6f2b/AHC22-00090f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/f03340810f4d/AHC22-00090f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/71a0afeaab5c/AHC22-00090f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/20313651eca9/AHC22-00090f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/76f0043adc60/AHC22-00090f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/e99dbcf324ac/AHC22-00090f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba4/9840471/9e78b4e1f5e2/AHC22-00090f09.jpg

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