Although it is known that prenatal maternal stress (PNMS) has a negative influence on nervous system development in offspring, there is no conclusive evidence clarifying its impact on early neurogenesis during development. In this study, we established a chick embryo model to investigate how PNMS affects early neurogenesis by mimicking an intrauterine environment with elevated dexamethasone levels. The results showed that dexamethasone-mimicked PNMS significantly suppressed the development of gastrula embryos and increased the risks of neural tube defects and cranial deformity. Using immunofluorescence staining and Western blots to evaluate the expression levels of pHIS3 and PCNA/Sox2, we found that PNMS significantly inhibited the proliferation of neural progenitor cells and that the downregulation of TGF-β signaling pathway might be responsible for the inhibition. Furthermore, immunofluorescence staining and Western blots manifested that PNMS could suppress the differentiation of neural progenitor cells to neuronal lineages, but promote them to transform into neuroglial cells, which might be due to the restriction of expressions of key genes (BMP4, SHH, Wnt3a, Slug, and Msx1) related to neural differentiation. In summary, our data reveal that PNMS dramatically impacts the earliest stages of neural development, thereby greatly increasing the risk of physical and mental health problems in childhood or adulthood.
Keywords: dexamethasone (Dex); glucocorticoids; neural progenitor cells; neurogenesis; prenatal maternal stress (PNMS).
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. See the journal About page for additional terms.