Maternal obesity induces activator protein 1-mediated inflammatory response to impair embryonic neurogenesis.
Overview
- Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA
- School of Food Science Washington State University Pullman Washington USA
Abstract
Abstract: Maternal 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.
Key points: Maternal obesity (MO) suppresses neurogenesis in the early embryos. Single‐cell RNA sequencing (scRNA‐seq) reveals decreased neurogenic cells and neurogenic factors in MO embryos. MO elevates activator protein 1 (AP‐1) transcription factor accessibility to the promoters of inflammatory genes. Inflammation induced by tumour necrosis factor‐α (TNF‐α) suppresses Neurod1 and Neurog2 expression and neurogenesis in vitro.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE278631, at NCBI GEO; found in “Data availability statement”
Data availability statement
The data for this study are available in the Gene Expression Omnibus (GEO), under accession number GSE278631, https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 5 keywords, 15 MeSH terms, 1 funder, 50 references.
Cite
This paper
Chen, L., Hossain, M. N., Gao, Y., Kou, Z., Islam, S., Li, X., Shin, C., de Avila, J. M., Zhu, M., & Du, M. (2026). Maternal obesity induces activator protein 1-mediated inflammatory response to impair embryonic neurogenesis. The Journal of physiology, 604(7), 3159-3174. https://
BibTeX
@article{chen2026materna
author = {Chen, Li‐Wei and Hossain, Md Nazmul and Gao, Yao and Kou, Zhongyun and Islam, Sharmeen and Li, Xinrui and Shin, Chaeyoung and de Avila, Jeanene Marie and Zhu, Mei‐Jun and Du, Min},
title = {{Maternal obesity induces activator protein 1-mediated inflammatory response to impair embryonic neurogenesis}},
journal = {The Journal of physiology},
year = {2026},
month = mar,
volume = {604},
number = {7},
pages = {3159--3174},
publisher = {Wiley},
issn = {0022-3751},
doi = {10.1113/
url = {https://
pmid = {41823327},
pmcid = {PMC13039269}
}
RIS
TY - JOUR
AU - Chen, Li‐Wei
AU - Hossain, Md Nazmul
AU - Gao, Yao
AU - Kou, Zhongyun
AU - Islam, Sharmeen
AU - Li, Xinrui
AU - Shin, Chaeyoung
AU - de Avila, Jeanene Marie
AU - Zhu, Mei‐Jun
AU - Du, Min
TI - Maternal obesity induces activator protein 1-mediated inflammatory response to impair embryonic neurogenesis
T2 - The Journal of physiology
J2 - J Physiol
PY - 2026
DA - 2026/
VL - 604
IS - 7
SP - 3159
EP - 3174
SN - 0022-3751
PB - Wiley
DO - 10.1113/
UR - https://
LA - en
ER -
CSL-JSON
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