铝暴露干扰胚胎早期发育过程中的表观遗传修饰和细胞器功能。

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiao-Ting Yu , Zhen-Hui Fu , Wen-Lin Pan , Yan-Lun Song , Rui-Jie Ma , Hao-Lin Zhang , Xing-He Ke , Shao-Chen Sun , Jun-Li Wang , Lin-Lin Hu
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引用次数: 0

摘要

铝是一种轻质耐腐蚀的金属元素,广泛应用于工业、建筑、食品和制药等领域,对神经系统、骨骼系统、生殖系统、血液系统和免疫系统等多个器官系统产生不利影响。本研究探讨了铝暴露对哺乳动物胚胎发育的影响。我们的数据表明,铝暴露诱导小鼠早期胚胎发育缺陷,包括合子和2细胞阶段的缺陷,导致一般转录活性降低。我们发现线粒体功能障碍和活性氧(ROS)水平显著增加,从而引发氧化应激,这种氧化应激随后导致DNA损伤。此外,我们观察到组蛋白修饰水平的实质性改变,特别是H3K4me2、H3K4me3、H3K27me3和H4K12ac。这些组蛋白修饰的变化被发现与观察到的DNA损伤和线粒体功能障碍密切相关。我们还观察到溶酶体、内质网和高尔基体的异常分布,表明铝可能干扰胚胎中的蛋白质修饰和运输。综上所述,我们的研究结果表明,铝暴露通过诱导线粒体氧化应激破坏小鼠胚胎早期发育,从而进一步导致小鼠胚胎DNA损伤、组蛋白修饰异常和细胞器功能异常。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Aluminum exposure disturbs epigenetic modification and organelle function during early embryo development
Aluminum is a lightweight and corrosion-resistant metal element that is widely used in industries, construction, food, and pharmaceuticals, and it can adversely affect multiple organ systems including the nervous system, skeletal system, reproductive system, blood system, and immune system. In present study, we investigated the effects of aluminum exposure on mammalian embryo development. Our data demonstrate that aluminum exposure induces mouse early embryo development defects, including those at the zygotes and 2-cell stages, causing a decrease in general transcription activity. We found mitochondrial dysfunction and a significant increase in reactive oxygen species (ROS) levels, thereby triggering oxidative stress, and this oxidative stress subsequently results in DNA damage. Additionally, we observed substantial alterations in histone modification levels, specifically H3K4me2, H3K4me3, H3K27me3, and H4K12ac. These changes in histone modifications were found to be closely associated with the observed DNA damage and mitochondrial dysfunction. We also observed aberrant distribution of lysosomes, endoplasmic reticulum, and Golgi apparatus, indicating that aluminum could disturb protein modification and transport in embryos. In conclusion, our results indicated that aluminum exposure disrupted early embryo development by inducing mitochondria-based oxidative stress, which further caused DNA damage, aberrant histone modifications and organelle functions in mouse embryos.
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来源期刊
CiteScore
7.70
自引率
3.90%
发文量
410
审稿时长
36 days
期刊介绍: Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
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