Valproic Acid Triggers Embryonic Cell Senescence, Explaining Birth Defects and Autism Risk

Researchers using mice and human organoids show valproic acid (VPA) can force developing neuroepithelial cells to enter senescence via the p19Arf pathway, shrinking the neural progenitor pool and causing defects such as microcephaly and neural tube problems; removing p19Arf in mice reduces some VPA-related effects, including autism-linked gene changes, but other abnormalities persist, indicating multiple developmental pathways are disrupted and highlighting a potential link between misregulated senescence and birth defects and autism risk.