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.
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.
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.
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.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |