关键词: BHPF Fluorene-9-bisphenol Mouse embryonic stem cells Terminal differentiation

来  源:   DOI:10.1016/j.crtox.2023.100133   PDF(Pubmed)

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.
摘要:
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)自我更新的影响,多能性,和分化仍然知之甚少。这项研究调查了BHPF对小鼠胚胎干细胞(mESCs)和胚胎体(EBs)的影响。我们的结果表明,BHPF暴露导致mESCs的形态变化,减少圆顶形菌落的百分比,并表明自我更新和多能性的丧失。BHPF暴露也似乎影响EB形成的早期阶段及其生长动力学,随着EB数量的减少和它们的大小的增加。随后的基因表达分析揭示BHPF暴露导致炎性基因Il6的表达增加,表明潜在的应激反应。此外,BHPF影响终末分化途径,调节与不同细胞类型相关的16个基因的表达,包括淋巴内皮,角质形成细胞上皮,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,肾单位近端小管细胞,和心肌细胞。这些发现为BHPF对ESC生物学的影响提供了见解,并暗示了对发育和神经退行性疾病的潜在影响。未来的工作应该集中在阐明BHPF介导的对干细胞功能的影响的潜在机制。这可能为了解BHPF环境暴露对健康的影响提供新的视角。
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