关键词: Apoptosis disorder Cigarette smoke extract Lipid metabolism RNA-seq

Mesh : Animals Female Zebrafish / genetics metabolism Embryo, Nonmammalian / metabolism MicroRNAs / genetics metabolism RNA, Messenger / genetics metabolism Environmental Pollutants / metabolism pharmacology

来  源:   DOI:10.1186/s12967-024-05050-9   PDF(Pubmed)

Abstract:
Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants\' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.
摘要:
烟草污染物在环境中普遍存在,导致孕妇无意中暴露。这些污染物对胚胎发育的毒性作用的研究尚未完全阐明潜在的潜在机制。因此,在这项研究中,我们旨在通过斑马鱼胚胎毒性试验和microRNA(miRNA)和信使RNA(mRNA)的整合转录组学分析,研究浓度为0.25,1和2.5%的香烟烟雾提取物(CSE)诱导的发育毒性.研究结果表明,CSE引起发育毒性,包括死亡率上升和潜伏率下降,以剂量依赖的方式。此外,CSE诱导的畸形和凋亡,特别是斑马鱼幼虫的头部和心脏。我们使用mRNA和miRNA测序分析来比较斑马鱼幼虫中基因和miRNA表达的变化。生物信息学分析表明,CSE诱导的发育毒性的潜在机制与受损的遗传物质损伤修复有关,细胞凋亡失调,和脂质代谢紊乱。富集分析和RT-qPCR表明ctsba基因在胚胎发育凋亡中起着至关重要的作用。fads2基因主要调节脂质代谢毒性。这项研究的结果提高了对斑马鱼胚胎中CSE诱导的发育毒性的理解,并有助于在早期胚胎发育过程中制定针对烟草污染物的新型预防策略。
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