REVIEW article
Front. Med.
Sec. Obstetrics and Gynecology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1539651
This article is part of the Research TopicAdvancements in Understanding and Managing Preeclampsia: Exploring Molecular Mechanisms, Biomarkers, and Clinical ImplicationsView all 11 articles
Multidimensional Roles of cfDNA Fragmentomics in Preeclampsia: From Placental Hypoxia and TLR9 Inflammation to Clinical Risk Stratification
Provisionally accepted
- Changzhou Maternal and Child Health Care Hospital, Changzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Cell-free DNA (cfDNA) has emerged as a pivotal biomarker for predicting preeclampsia (PE),a multisystem syndrome characterized by placental hypoperfusion and systemic inflammation. This review synthesizes critical advances in the field, highlighting quantitative alterations in cfDNA, fragmentomic profiles, and placenta-specific methylation patterns (e.g., RASSF1A) that demonstrate significant value for early prediction and severity stratification of PE. Mechanistically, placental hypoxia-induced trophoblast apoptosis (releasing cfDNA), epigenetic dysregulation activating TLR9/NF-κB inflammatory pathways, and oxidative stress-mediated mitochondrial cfDNA fragmentation collectively drive disease progression. In clinical translation, integrating cfDNA with complementary biomarkers enhances predictive performance, though limitations persist regarding preanalytical variability and dynamic gestational changes. Future efforts must advance fragmentomics-integrated multi-omics frameworks for precision prediction, where assay standardization constitutes the fundamental translational bottleneck.
Keywords: cell-free DNA, Preeclampsia, Placenta, Fragmentomics, Methylation
Received: 04 Dec 2024; Accepted: 02 Sep 2025.
Copyright: © 2025 Guo, Zhang, Yang and Wang. 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: Li Wang, Changzhou Maternal and Child Health Care Hospital, Changzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.