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整合单细胞RNA测序以探究孕期接触氯氟氰菊酯对后代神经发育的毒性:神经干细胞的命运抉择

Integrating scRNA-seq to explore offspring neurodevelopmental toxicity induced by Cyfluthrin exposure during pregnancy: A fate decision for NSCs.

作者信息

Gao Haoxuan, Tian Xueyan, Wu Bing, Geng Xiaozhe, Chen Yue, Song Yanan, Yan Yucheng, Li Xiaoyu, Ni Wensi, Zhao Ji, Yang Huifang

机构信息

School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia 750004, China.

School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia 750004, China.

出版信息

J Hazard Mater. 2025 Jul 15;492:138205. doi: 10.1016/j.jhazmat.2025.138205. Epub 2025 Apr 7.

Abstract

Cyfluthrin is a widely used insecticide, and studies have shown that its exposure during pregnancy is associated with neurobehavioral abnormalities in offspring, but the mechanism of toxicity is unknown. In this study, we observed the neurodevelopmental toxicity of Cyfluthrin in rat offspring of different ages due to pregnancy exposure, which manifested a series of impairments such as persistent cognitive impairment, neuronal loss in hippocampal tissues, synaptic damage, and altered expression of neurodevelopmental-related factors. Hippocampal scRNA-seq in neonatal rats showed specific cellular responses to prenatal Cyfluthrin exposure. Through DEG intergroup difference analysis, intercellular communication analysis, and mimetic timing analysis, we found that the change in the fate of neural stem cells - alterations in differentiation direction, proliferation, and apoptosis levels - was the main cause of the offspring's developmental toxicity induced by prenatal Cyfluthrin exposure. This inference was verified by our in - vivo and ex - vivo experiments. Our study first constructed a single - cell atlas of the offspring's brain hippocampus exposed to Cyfluthrin during pregnancy. It warns about pesticide intake during pregnancy and nursing in women and provides a theoretical basis for neurodevelopmental toxicity from early - life exposure to environmental pollutants.

摘要

氯氟氰菊酯是一种广泛使用的杀虫剂,研究表明,孕期接触该物质与后代的神经行为异常有关,但其毒性机制尚不清楚。在本研究中,我们观察了孕期接触氯氟氰菊酯对不同年龄大鼠后代的神经发育毒性,表现为一系列损害,如持续性认知障碍、海马组织神经元丢失、突触损伤以及神经发育相关因子表达改变。新生大鼠的海马单细胞RNA测序显示了对产前氯氟氰菊酯暴露的特定细胞反应。通过差异基因(DEG)组间差异分析、细胞间通讯分析和模拟时序分析,我们发现神经干细胞命运的改变——分化方向、增殖和凋亡水平的改变——是产前氯氟氰菊酯暴露诱导后代发育毒性的主要原因。我们的体内和体外实验验证了这一推断。我们的研究首次构建了孕期接触氯氟氰菊酯的后代脑海马单细胞图谱。它为孕期和哺乳期女性的农药摄入敲响了警钟,并为早期接触环境污染物导致的神经发育毒性提供了理论依据。

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