| Title: | High-fat diet-induced maternal pre-pregnancy obesity impairs decidual angiogenesis via an Hnrnpa2b1/mPGES-1/PGE2 axis-dependent disruption of stromal-vascular VEGFA signaling |
| Journal: | Genes & Diseases |
| Published: | 1 May 2026 |
| DOI: | https://doi.org/10.1016/j.gendis.2026.102242 |
Publication 20194
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Abstract
Maternal pre-pregnancy obesity is a well-established risk factor for a spectrum of adverse pregnancy outcomes, yet the molecular mechanisms through which obesity disrupts the early endometrial microenvironment have remained incompletely understood. Although placental abnormalities in obesity are well-documented, the developmental origins of these defects - particularly the molecular events during embryo implantation and decidualization that establish the foundation for normal placentation - have received limited attention. Here, integrating UK Biobank data with mechanistic studies in experimental models, we demonstrate that high-fat diet-induced pre-pregnancy obesity and high-fat exposure disrupt decidual angiogenesis by impairing stromal-endothelial communication. Specifically, high-fat exposure suppresses Hnrnpa2b1 binding to the mPGES-1 promoter, inhibiting prostaglandin E2 (PGE2) synthesis and subsequent vascular endothelial growth factor A secretion from stromal cells and leading to defective vascularization. Functional rescue experiments, including 3D biomimetic chip co-culture systems and targeted in vivo overexpression, confirm that restoring the Hnrnpa2b1/mPGES-1/PGE2 axis reinstates angiogenic competence and improves pregnancy outcomes. Our findings reveal a previously unrecognized metabolic-transcriptional cascade linking high-fat diet-induced obesity to endometrial vascular fragility and propose new diagnostic and therapeutic strategies for obesity-related reproductive failure.</p>
18 Authors
- Jing Long
- Xiangjun Chen
- Weike Li
- Ji Wang
- Sujuan Guo
- Liping Tan
- Chao Tong
- Chuan Peng
- Xuemei Chen
- Fei Han
- Yanqing Geng
- Taihang Liu
- Fangfang Li
- Junlin He
- Yingxiong Wang
- Zhenyin Chen
- Jinbo Hu
- Rufei Gao
1 Application
| Application ID | Title |
|---|---|
| 103654 | Environmental and genetic risk factors and target organ damage of resistant hypertension |
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