From population cohort to cellular mechanisms: prenatal estriol exposure induces autism spectrum disorder in offspring via disrupting the Notch signaling pathway and neuronal proliferation

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