["The Journal of Physiology, Volume 604, Issue 7, Page 3159-3174, 1 April 2026. ", "\nAbstract figure legend Maternal obesity (MO) creates a pro‐inflammatory embryonic environment, which activates the activator protein 1 (AP‐1) transcription factor complex, resulting in reduced expression of key neurogenic regulators and impaired neuronal differentiation. Consequently neuronal populations decrease due to MO during early neurogenesis. Together these findings reveal an inflammation‐driven transcriptional mechanism linking MO to disrupted embryonic neurogenesis. Figure created using BioRender.\n\n\n\n\n\n\n\n\n\nAbstract\nMaternal obesity (MO) is a growing global problem, which poses significant risks to fetal neurodevelopment and long‐term neurological functions of offspring, but the underlying molecular mechanisms remain to be established. To address this female mice were fed either a control diet or a high‐fat diet (HFD) for 2 months to induce obesity, and the same dietary treatments were maintained during pregnancy. Embryos were sampled at E11.5 and E13.5. Single‐cell RNA sequencing revealed reduced proportions of neurons and neural progenitors in embryos from obese mothers. The downregulation of neurogenesis, nervous system development and synaptic organization pathways were further confirmed by Gene Ontology analysis. Key neurogenic transcription factors, including Neurod1, Neurog2 and Ascl1, were suppressed in MO embryos, accompanied by increased expression of inflammatory markers, including tumour necrosis factor‐α (TNF‐α) and Cxcl2, and inflammatory signalling mediators, Fos, Jun and Jund. Single‐cell ATAC sequencing revealed the activator protein 1 (AP‐1) binding sites in the promoter regions of Tnf and Cd68, with MO‐enhancing AP‐1 transcription factor motif activity and increased chromatin accessibility in the loci of Tnfa and Cd68 genes. Furthermore, TNF‐α treatment of neurogenic cells suppressed Neurod1 and Neurog2 expression, suggesting a direct link between inflammatory signalling and impaired neurogenesis. Our findings suggest that MO creates a pro‐inflammatory environment that disrupts neurogenesis during early embryonic development, providing new insights into the neurodevelopmental disorders in offspring born to obese mothers.\n\n\n\n\n\n\n\n\n\nKey points\n\nMaternal obesity (MO) suppresses neurogenesis in the early embryos.\nSingle‐cell RNA sequencing (scRNA‐seq) reveals decreased neurogenic cells and neurogenic factors in MO embryos.\nMO elevates activator protein 1 (AP‐1) transcription factor accessibility to the promoters of inflammatory genes.\nInflammation induced by tumour necrosis factor‐α (TNF‐α) suppresses Neurod1 and Neurog2 expression and neurogenesis in vitro.\n\n\n"]