Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets

Ferroptosis is characterized as a specialized type of regulated cellular death that relies on iron and lipid peroxidation, which has recently been highlighted as playing a crucial role in the etiology of recurrent miscarriage (RM). Ferroptosis in RM is driven by dysregulated iron metabolism and incr...

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Main Authors: Mohammad Masoud Khodaei, Zahra Noori, Fateme Zare, Ahmad Meshkin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1559300/full
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author Mohammad Masoud Khodaei
Zahra Noori
Fateme Zare
Ahmad Meshkin
author_facet Mohammad Masoud Khodaei
Zahra Noori
Fateme Zare
Ahmad Meshkin
author_sort Mohammad Masoud Khodaei
collection DOAJ
description Ferroptosis is characterized as a specialized type of regulated cellular death that relies on iron and lipid peroxidation, which has recently been highlighted as playing a crucial role in the etiology of recurrent miscarriage (RM). Ferroptosis in RM is driven by dysregulated iron metabolism and increased oxidative stress, resulting from impaired antioxidant defense, which leads to lipid peroxidation and consequent cell death in trophoblasts. The cellular changes compromise placental development and impair trophoblast invasion and maternal-fetal tolerance. Therapeutic interventions targeting ferroptosis are promising for the mitigation of its effects and improvement of pregnancy outcomes. Strategies include Glutathione Peroxidase 4 (GPX4) activity enhancement, glutathione replenishment, ferroptosis inhibitors, and iron metabolism modulation. Further, new strategies targeting non-coding RNAs, and epigenetic regulators emphasize ferroptosis as a viable therapeutic target. This review emphasizes the importance of ferroptosis in the pathophysiology of RM and highlights its potential for guiding innovative treatments.
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issn 2296-634X
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publisher Frontiers Media S.A.
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spelling doaj-art-86226c2bcfd14da79512f6566f61e7032025-08-20T03:09:57ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.15593001559300Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targetsMohammad Masoud KhodaeiZahra NooriFateme ZareAhmad MeshkinFerroptosis is characterized as a specialized type of regulated cellular death that relies on iron and lipid peroxidation, which has recently been highlighted as playing a crucial role in the etiology of recurrent miscarriage (RM). Ferroptosis in RM is driven by dysregulated iron metabolism and increased oxidative stress, resulting from impaired antioxidant defense, which leads to lipid peroxidation and consequent cell death in trophoblasts. The cellular changes compromise placental development and impair trophoblast invasion and maternal-fetal tolerance. Therapeutic interventions targeting ferroptosis are promising for the mitigation of its effects and improvement of pregnancy outcomes. Strategies include Glutathione Peroxidase 4 (GPX4) activity enhancement, glutathione replenishment, ferroptosis inhibitors, and iron metabolism modulation. Further, new strategies targeting non-coding RNAs, and epigenetic regulators emphasize ferroptosis as a viable therapeutic target. This review emphasizes the importance of ferroptosis in the pathophysiology of RM and highlights its potential for guiding innovative treatments.https://www.frontiersin.org/articles/10.3389/fcell.2025.1559300/fullferroptosisrecurrent miscarriage (RM)therapeutic interventionstrophoblast dysfunctionglutathione peroxidase 4
spellingShingle Mohammad Masoud Khodaei
Zahra Noori
Fateme Zare
Ahmad Meshkin
Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets
Frontiers in Cell and Developmental Biology
ferroptosis
recurrent miscarriage (RM)
therapeutic interventions
trophoblast dysfunction
glutathione peroxidase 4
title Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets
title_full Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets
title_fullStr Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets
title_full_unstemmed Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets
title_short Ferroptosis and recurrent miscarriage: a critical review of pathophysiology and emerging therapeutic targets
title_sort ferroptosis and recurrent miscarriage a critical review of pathophysiology and emerging therapeutic targets
topic ferroptosis
recurrent miscarriage (RM)
therapeutic interventions
trophoblast dysfunction
glutathione peroxidase 4
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1559300/full
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AT fatemezare ferroptosisandrecurrentmiscarriageacriticalreviewofpathophysiologyandemergingtherapeutictargets
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