Evidence map›Paper›PMID 41398693›Full record

ArticleEuropean journal of medical research2025

Pre-eclampsia-related TLR2/4 signaling activates NOX2/4 to induce oxidative stress and ferroptosis in trophoblasts.

Yan Zhang, Yunmei Ke, Baosheng Zhu, Zhuo Chen, Li Ren, Jinman Zhang, Jie Wu

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Article in European journal of medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Yan Zhang *Department of Medical Genetics, Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, China.
Yunmei Ke *Department of Reproductive Gynaecology, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Baosheng ZhuDepartment of Medical Genetics, Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, China.
Zhuo ChenDepartment of Obstetrics, The First Affiliated Hospital Medical Kunming Medical University, Kunming, Yunnan, China.
Li RenDepartment of Reproductive Gynaecology, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Jinman Zhang *Department of Medical Genetics, Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, China. 171887587@qq.com.
Jie Wu *Department of Obstetrics, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, China. zhangyankmmc@163.com.

Funding

First people's Hospital of Yunnan province.National Key clinical specialty of Gynecology 2022FKZDZK-15First people`s Hospital of Yunnan Province. Yunnan Province clinical Research Center for Gynecological and Obstetric Disease 2023YJZX-FC11National Health Commission Key Laboratory of Preconception Health Birth in Western China.National Natural Science Foundation of China 82260645the Combined Applied Scientific Research Projects of the Department of Science and Technology of Kunming Medical College 202101AY070001-242the Combined Applied Scientific Research Projects of the Department of Science and Technology of Kunming Medical College 202101AY070001-264Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases 2024CSKFKT-02
6 · The paper itself

Abstract

backgroundOxidative stress and ferroptosis have been recognized as detrimental factors in trophoblast malfunction in pre-eclampsia (PE). Here, we investigated the roles of toll-like receptor (TLR) signaling in PE-induced ferroptosis in the placenta tissues and explored the therapeutic potential of targeting TLR signaling in the animal model of PE.

methodsPlacental tissues from 20 PE patients and 20 healthy controls were analyzed for TLR2/4 expression and MAPK signaling activation using Western blot and transmission electron microscopy. HTR-8/SVneo trophoblasts were subjected to hypoxia/reoxygenation (H/R) induction to mimic PE conditions. Cell proliferation (CCK-8 assay), migration (scratch assay), invasion (transwell assay), and angiogenesis (tube formation assay) were assessed. Ferroptosis markers were evaluated by Western blot, and oxidative stress parameters including reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and labile iron were measured using commercial kits. In vivo, a reduced uterine perfusion pressure (RUPP) rat model of PE (n = 6 per group) was established on gestational day 14, and animals were treated with robinin (TLR2/4 inhibitor, 5 mg/kg/day) or VAS2870 (NADPH oxidase [NOX] inhibitor, 5 mg/kg/day) via intraperitoneal injection. Blood pressure, proteinuria, coagulation parameters, and placental ferroptosis markers were analyzed on gestational day 18.

resultsTLR2/4 upregulation and mitogen-activated protein kinase (MAPK) signaling over-activation were found in the placental tissues of PE patients and in H/R-induced trophoblasts. Inhibiting TLR2/4 reduced MAPK signaling and improved trophoblast proliferation, migration, invasion, and angiogenesis. TLR2/4-dependent NADPH oxidase 2 and 4 (NOX2 and NOX4) upregulation contributed to the oxidative stress and ferroptosis in trophoblasts upon H/R induction. In the rat model of PE, inhibiting TLR2/4 and NOX activity prevented ferroptotic events in the placental tissues and ameliorated PE syndromes, including elevated blood pressure and proteinuria.

conclusionsTLR2/4-dependent oxidative stress and ferroptosis may undermine trophoblast function in the PE placenta, and targeting TLR signaling-mediated ferroptosis could serve as an intervention strategy of PE.

Indexed as

FerroptosisNADPH Oxidase 2NADPH Oxidase 4Oxidative StressPre-EclampsiaToll-Like Receptor 2Toll-Like Receptor 4TrophoblastsAdultAnimalsFemaleHumansPlacentaPregnancyRatsRats, Sprague-DawleyCYBB protein, humanNADPH Oxidase 2NADPH Oxidase 4NOX4 protein, humanTLR2 protein, humanTLR4 protein, humanToll-Like Receptor 2Toll-Like Receptor 4FerroptosisOxidative stressPre-eclampsiaToll-like receptor (TLR)Trophoblasts

Identifiers

PMID41398693
PMCPMC12821286

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.