REVIEW article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1559300
Ferroptosis and Recurrent Miscarriage: A Critical Review of Pathophysiology and Emerging Therapeutic Targets
Provisionally accepted
- Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, yazd, Iran
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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.
Keywords: ferroptosis, Recurrent Miscarriage (RM), Therapeutic interventions, Trophoblast dysfunction, glutathione peroxidase 4
Received: 12 Jan 2025; Accepted: 29 May 2025.
Copyright: © 2025 Khodaei, Noori and Zare. 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: Fateme Zare, Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, yazd, Iran
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