ORIGINAL RESEARCH article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1627057
This article is part of the Research TopicMaternal-fetal-placental Immune Interactions: Implications for Pregnancy Outcomes and Long-term HealthView all 21 articles
Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas
Provisionally accepted
Qianghua WangXuegu WangJiaojiao FeiChuanyue JiangYafen Tao
Nana YangHuijuan ChenChengli DouBiao Ding
Danli Du
Xiang Li*- The first affiliated hospital of Bengbu medical university, Bengbu, China
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Background: Early-onset preeclampsia (EOPE) is a severe form of preeclampsia that mainly contributes to maternal and perinatal morbidity and mortality worldwide. This study aimed to systematically analyze the expression and function of ferroptosis-related gene HILPDA in EOPE placentas.We included five transcriptomic datasets (GSE148241, GSE44711, GSE74341, GSE114691, GSE10588) downloaded from the Gene Expression Omnibus (GEO) in this study. Using differential expression analysis, weighted gene coexpression network analysis (WGCNA), and machine learning models (LASSO, SVM-RFE, Random Forest), We identified hub genes and diagnostic biomarkers. We performed functional enrichment (GO and KEGG) and immune infiltration analysis to elucidate molecular mechanisms. Experimental validation included Western blot on clinical placental samples and siRNA-mediated knockdown in HTR-8/SVneo trophoblasts to assess migration. Results: We observed HILPDA upregulation and confirmed its diagnostic accuracy (AUC=0.71) in EOPE placentas. Functional analysis revealed HILPDA-associated enrichment in immune regulation (leukocyte migration, MHC complexes) and cellular processes (collagen organization, HIF-1 signaling). Throuth WGCNA, we identified 171 HILPDA-associated DEGs. Machine learning prioritized PART1 as diagnostic biomarkers. Immune profiling highlighted HILPDA's correlation with activated dendritic cells, neutrophils and resting mast cells. Experimentally, we confirmed HILPDA up-regulation in EOPE placentas and its critical role in suppressing trophoblast migration. Conclusions: Our study establishes HILPDA as a central mechanistic regulator involved in placental immune dysregulation and trophoblast migration in EOPE pathogenesis. The identified biomarkers PART1 and HILPDA-associated pathways may offer novel diagnostic and therapeutic targets for EOPE management, which contribute to reduce maternal morbidity and prevent perinatal mortality in this catastrophic pregnancy syndrome.
Keywords: Early-onset preeclampsia, HILPDA, Trophoblast migration, Immune infiltration, ferroptosis
Received: 12 May 2025; Accepted: 25 Jul 2025.
Copyright: © 2025 Wang, Wang, Fei, Jiang, Tao, Yang, Chen, Dou, Ding, Du and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiang Li, The first affiliated hospital of Bengbu medical university, Bengbu, China
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