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Maternal obesity induces activator protein 1-mediated inflammatory response to impair embryonic neurogenesis.

Overview

Authors: Li‐Wei Chen1, Md Nazmul Hossain1, Yao Gao1, Zhongyun Kou1, Sharmeen Islam1, Xinrui Li1, Chaeyoung Shin1, Jeanene Marie de Avila1, Mei‐Jun Zhu2, Min Du1
  1. Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA
  2. School of Food Science Washington State University Pullman Washington USA
Institutions: Washington State University (United States)
Journal: The Journal of physiology, volume 604, issue 7, pages 3159-3174
Dates: received 23 May 2025; accepted 24 February 2026; published online 13 March 2026; in print 1 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1113/jp289326 · PMID 41823327 · PMCID PMC13039269 · OpenAlex W7135176151
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population)
Methods: Statistics, Smoothing, state filtering, decompositions
Keywords: embryo, inflammation, maternal obesity, neurogenesis, neurogenic transcription factors
MeSH: Inflammation*, Neurogenesis*, Obesity*, Pregnancy in Obesity*, Transcription Factor AP-1*, Animals, Basic Helix-Loop-Helix Proteins, Developmental Origins of Health and Disease, Diet, High-Fat, Female, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Pregnancy, Tumor Necrosis Factor-alpha (* major topic)
Journal subjects: Placenta, pregnancy and perinatal physiology, Editor's Choice
Topic: Gestational Diabetes Research and Management (Obstetrics and Gynecology, Medicine), according to OpenAlex
Funding: NIH (R01HD067449)
Citations: cited by 1 paper (Europe PMC); 50 references in the paper

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.

Code

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Data

Datasets cited

Data availability statement

The data for this study are available in the Gene Expression Omnibus (GEO), under accession number GSE278631, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278631.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

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://doi.org/10.1113/jp289326

BibTeX

@article{chen2026maternal,
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/jp289326},
url = {https://doi.org/10.1113/jp289326},
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 - 2026/03/13
VL - 604
IS - 7
SP - 3159
EP - 3174
SN - 0022-3751
PB - Wiley
DO - 10.1113/jp289326
UR - https://doi.org/10.1113/jp289326
LA - en
ER -

CSL-JSON

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