Fluorene-9-bisphenol affects the terminal differentiation of mouse embryonic bodies

IF 2.9 Q2 TOXICOLOGY
Aidan J. McLaughlin , Anthony I. Kaniski , Darena I. Matti , Nicodemus C. Monear , Jessica L. Tischler , Besa Xhabija
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Abstract

Fluorene-9-bisphenol (BHPF) has recently attracted interest as it is increasingly used in industrial settings as a substitute for Bisphenol A (BPA). However, the effects of BHPF exposure on embryonic stem cell (ESC) self-renewal, pluripotency, and differentiation remain poorly understood. This study investigates the impacts of BHPF on mouse embryonic stem cells (mESCs) and embryonic bodies (EBs). Our results reveal that BHPF exposure leads to a morphological shift in mESCs, reducing the percentage of dome-shaped colonies and indicating loss of self-renewal and pluripotency. BHPF exposure also appeared to affect the early stages of EB formation and their growth dynamics, with a reduction in EB numbers and an increase in their size. Subsequent gene expression analysis revealed that BHPF exposure led to increased expression of the inflammatory gene Il6, indicating a potential stress response.

Furthermore, BHPF affected the terminal differentiation pathway, modulating the expression of 16 genes associated with distinct cell types, including lymphatic endothelium, keratinocyte epithelium, pancreatic beta cells, macrophages, monocytes, T-cells, neurons, retinal ganglion cells, nephrons proximal tubule cells, and cardiomyocytes. These findings offer insights into the impact of BHPF on ESC biology and suggest potential implications for developmental and neurodegenerative disorders. Future work should focus on elucidating the underlying mechanisms of BHPF-mediated effects on stem cell function. This may offer new perspectives for understanding the health impacts of environmental exposure to BHPF.

Abstract Image

芴-9-双酚影响小鼠胚胎体的终末分化
芴-9-双酚(BHPF)最近引起了人们的兴趣,因为它越来越多地用于工业环境中作为双酚a (BPA)的替代品。然而,BHPF暴露对胚胎干细胞(ESC)自我更新、多能性和分化的影响仍然知之甚少。本研究探讨了BHPF对小鼠胚胎干细胞(mESCs)和胚胎体(EBs)的影响。我们的研究结果表明,BHPF暴露导致mESCs的形态改变,减少圆顶状菌落的百分比,并表明自我更新和多能性的丧失。BHPF暴露似乎也影响EB形成的早期阶段及其生长动态,EB数量减少,大小增加。随后的基因表达分析显示,BHPF暴露导致炎症基因Il6的表达增加,表明潜在的应激反应。此外,BHPF影响了终末分化途径,调节了与不同细胞类型相关的16个基因的表达,包括淋巴内皮细胞、角化细胞上皮、胰腺β细胞、巨噬细胞、单核细胞、t细胞、神经元、视网膜神经节细胞、肾细胞近端小管细胞和心肌细胞。这些发现为BHPF对ESC生物学的影响提供了见解,并提出了对发育和神经退行性疾病的潜在影响。未来的工作应集中于阐明bhpf介导的干细胞功能影响的潜在机制。这可能为理解环境暴露于BHPF对健康的影响提供新的视角。
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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来源期刊
Current Research in Toxicology
Current Research in Toxicology Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
4.70
自引率
3.00%
发文量
33
审稿时长
82 days
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