陆军军医大学学报2026，Vol.48Issue(2)：138-146,9.DOI:10.16016/j.2097-0927.202511044
从人群队列到细胞机制:孕期雌三醇暴露通过干扰Notch信号通路和神经细胞增殖诱导子代自闭症谱系障碍
From population cohort to cellular mechanisms:prenatal estriol exposure induces autism spectrum disorder in offspring via disrupting the Notch signaling pathway and neuronal proliferation
摘要
Abstract
Objective To investigate the effect of prenatal estriol(E3)exposure on autism spectrum disorders(ASD)and the role of the Notch signaling pathway in the process.Methods Untargeted metabolomics was performed on plasma samples from 44 mothers of ASD children and 44 matched controls in the Guangxi Zhuang birth cohort.Then E3 was identified as main differential metabolite during pregnancy.SH-SY5Y cells were subjected and divided into a control group and study groups(10,30,50 and 100 µmol/L E3),and proteomics was performed to screen the main pathway involved in the process.CCK-8 assay was employed to detect cell proliferation.Western blotting and RT-qPCR were performed to verify the obtained pathway.Results Metabolomics analysis for plasma metabolite levels in pregnant women showed that the E3 level in the case group was significantly down-regulated than that of the control group(P<0.01).KEGG enrichment analysis indicated that the Notch signaling pathway was a significantly enriched pathway(P<0.01).CCK-8 assay suggested that the concentration of 100 µmol/L was identified as the most significant dose for E3 in the proliferation inhibition of SH-SY5Y cells(P<0.01).Both qPCR and Western blotting indicated that 100 µmol/L E3 treatment resulted in obvious down-regulation in Jagged1(P<0.01),Notch1(P<0.01),and Hes1(P<0.05)at mRNA and protein levels in SH-SY5Y cells.Conclusion Prenatal E3 exposure may be associated with ASD,and its mechanism may be through inhibiting the Notch signaling pathway,and thereby inhibiting neural cell proliferation.关键词
雌三醇/自闭症谱系障碍/人神经母细胞瘤细胞/Notch信号通路/代谢组学/蛋白组学Key words
estriol/autism spectrum disorder/SH-SY5Y cells/Notch signaling pathway/metabolomics/proteomics分类
医药卫生引用本文复制引用
冉光辉,宋安华,韦丽娟,刘丽丽,李钟意,蓝利琪,黄欣蕾,曾小云,王丽君..从人群队列到细胞机制:孕期雌三醇暴露通过干扰Notch信号通路和神经细胞增殖诱导子代自闭症谱系障碍[J].陆军军医大学学报,2026,48(2):138-146,9.基金项目
广西科技计划项目(2024GXNSFDA999004,GuikeAD23026297) （2024GXNSFDA999004,GuikeAD23026297）
广西青年科技人才工程资助(GXYESS2025001) Supported by the Project of Science and Technology Program of Guangxi Province(2024GXNSFDA999004,GuikeAD23026297)and the Project of Young Scientific and Technological Talent Program of Guangxi Program(GXYESS2025001). （GXYESS2025001）
