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丙烯酰胺暴露会导致斑马鱼和大鼠胚胎骨骼发育毒性。

Exposure to acrylamide induces skeletal developmental toxicity in zebrafish and rat embryos.

机构信息

National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China.

Department of Nutrition and Food Hygiene, School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

出版信息

Environ Pollut. 2021 Feb 15;271:116395. doi: 10.1016/j.envpol.2020.116395. Epub 2020 Dec 24.

DOI:10.1016/j.envpol.2020.116395
PMID:33418285
Abstract

Acrylamide is a well-known carcinogen and neurotoxic substance that has been discovered in frying or baking carbohydrate-rich foods and is widely found in soils and groundwater. The purpose of this study was to investigate the adverse effects of exposure to acrylamide on skeletal development. After treatment with acrylamide in zebrafish embryos, the survival and hatching rates decreased, and the body length shortened, with cartilage malformation and a decrease in skeletal area. Exposure to acrylamide in maternal rats during the lactation period disturbed bone mineral density, serum levels of parathyroid hormone, and the expression of skeletal development-related genes in neonates. Exposure to acrylamide in pregnant rats during the pregnancy period decreased the trabecular density and inhibited cartilage formation by delaying the differentiation of osteoblasts and promoting the maturation of osteoclasts in rat embryos. Furthermore, acrylamide intervention downregulated the expression of chondrocyte and osteoblast differentiation-related genes (sox9a, bmp2, col2a1, and runx2), and upregulated the expression of osteoclast marker genes (rankl and mcsf) in zebrafish and rat embryos at different gestational stages. Our results indicated that exposure to acrylamide dysregulated signature gene and protein expression profiles of skeletal development by suppressing the differentiation and maturation of osteoblasts and cartilage matrix and promoting the formation of osteoclasts, and ultimately induced skeletal abnormality in morphology, which brings increasing attention to the intergenerational toxicity of acrylamide via mother-to-child transmission.

摘要

丙烯酰胺是一种已知的致癌物质和神经毒物,已在油炸或烘焙富含碳水化合物的食物中发现,并广泛存在于土壤和地下水中。本研究旨在探讨接触丙烯酰胺对骨骼发育的不良影响。在斑马鱼胚胎中用丙烯酰胺处理后,存活率和孵化率下降,体长缩短,软骨畸形,骨面积减少。哺乳期母鼠暴露于丙烯酰胺会干扰新生儿的骨矿物质密度、甲状旁腺激素水平和骨骼发育相关基因的表达。妊娠期间母鼠暴露于丙烯酰胺会降低骨小梁密度,并通过延迟成骨细胞分化和促进破骨细胞成熟来抑制软骨形成。此外,丙烯酰胺干预下调了软骨细胞和成骨细胞分化相关基因(sox9a、bmp2、col2a1 和 runx2)在不同胎龄斑马鱼和大鼠胚胎中的表达,并上调了破骨细胞标记基因(rankl 和 mcsf)的表达。我们的结果表明,丙烯酰胺通过抑制成骨细胞和软骨基质的分化和成熟以及促进破骨细胞的形成,扰乱了骨骼发育的特征基因和蛋白表达谱,最终导致形态上的骨骼异常,这引起了人们对通过母婴传播的丙烯酰胺的代际毒性的日益关注。

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