Ferroptosis in health and disease.
7 affiliations
- 1Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
- 2Reproductive Biology and Toxicology Research Laboratory (ReBTReL), Oasis of Grace Hospital, Osogbo, Nigeria.
- 3Cardiovascular Regenerative Medicine & Tissue Engineering 3D Lab, Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
- 4Breeding and Genetic Unit, Department of Agronomy, Osun State University, Osun State, Nigeria.
- 5Department of Physiology, Babcock University, Ilishan Remo, Ogun State, Nigeria.
- 6Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria. [email protected].
- 7Reproductive Biology and Toxicology Research Laboratory (ReBTReL), Oasis of Grace Hospital, Osogbo, Nigeria. [email protected].
Abstract
Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death that is driven by lipid peroxidation. In the past decade, it has emerged as a core pathogenic mechanism in a wide range of human diseases, such as neurodegenerative disorders, cardiovascular disease, cancer, and notably, reproductive dysfunction. This review provides a comprehensive overview of the molecular mechanisms underlying ferroptosis with a specific focus on the System Xc⁻-GSH-GPX4 axis, iron metabolism, lipid peroxidation, and the regulatory roles of key modulators such as Nrf2, ACSL4, and CISD2. This review also explores the physiological roles of ferroptosis in development, tissue homeostasis, and immune regulation, as well as its pathological contributions to obesity, diabetes mellitus, atherosclerosis, neurodegeneration, stroke, cancer, infectious diseases, and reproductive disorders. A substantial part of this review discusses the role of ferroptosis in the pathogenesis of reproductive disorders, such as male reproductive pathologies, including varicocele, testicular ischemia-reperfusion, cryptorchidism, oligospermia, erectile dysfunction, and testicular cancer, and female pathologies like primary ovarian insufficiency, polycystic ovary syndrome, endometriosis, ovarian cancer, and pre-eclampsia. Moreover, the interplay between ferroptosis and immune dysfunction in reproductive tract infections was highlighted. Furthermore, we evaluated current biomarkers, emerging therapeutic strategies, and key translational challenges, highlighting the promise of ferroptosis-modulating agents for novel diagnostic and therapeutic interventions in reproductive medicine and beyond.
Related
- SGLT2 inhibitors attenuate diabetic kidney disease by suppressing YAP dependent ferroptosis
- Mitophagy and Ferroptosis in Diabetic Kidney Disease: A Hypothesis of Their Synergistic Interplay in Renal Tubular Injury—A Narrative Review
- Targeting ferroptosis in rotenone-induced Parkinson’s disease: from mechanistic insights to pharmacological interventions
- ZFP36-ferroptosis axis as a key renal protective pathway in diabetic kidney disease
- Targeting Hippocampal PTEN Suppresses Ferroptosis and Rescues Cognitive Decline in Alzheimer's Disease via Dual AKT/GSK3β/Nrf2 and AKT/STAT3 Axes
BibTeX
@article{oyedokun2026ferroptosis,
title = {{Ferroptosis in health and disease.}},
author = {Precious Adeoye Oyedokun and Victory Jesutoyosi Ashonibare and Tunmise Maryanne Akhigbe and Precious Jesutofunmi Ashonibare and Adetomiwa Ezekiel Adeogun and Cecilia Adedeji Adegbola and Ayomide Isaac Omole and Roland Eghoghosoa Akhigbe},
journal = {Molecular biomedicine},
year = {2026},
month = oct,
doi = {10.1186/s43556-026-00637-8},
url = {https://europepmc.org/article/MED/42920026},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ferroptosis in health and disease.
AU - Precious Adeoye Oyedokun
AU - Victory Jesutoyosi Ashonibare
AU - Tunmise Maryanne Akhigbe
AU - Precious Jesutofunmi Ashonibare
AU - Adetomiwa Ezekiel Adeogun
AU - Cecilia Adedeji Adegbola
AU - Ayomide Isaac Omole
AU - Roland Eghoghosoa Akhigbe
PY - 2026
DA - 2026/10/24
JO - Molecular biomedicine
DO - 10.1186/s43556-026-00637-8
UR - https://europepmc.org/article/MED/42920026
AB - Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death that is driven by lipid peroxidation. In the past decade, it has emerged as a core pathogenic mechanism in a wide range of human diseases, such as neurodegenerative disorders, cardiovascular disease, cancer, and notably, reproductive dysfunction. This review provides a comprehensive overview of the molecular mechanisms underlying ferroptosis with a specific focus on the System Xc⁻-GSH-GPX4 axis, iron metabolism, lipid peroxidation, and the regulatory roles of key modulators such as Nrf2, ACSL4, and CISD2. This review also explores the physiological roles of ferroptosis in development, tissue homeostasis, and immune regulation, as well as its pathological contributions to obesity, diabetes mellitus, atherosclerosis, neurodegeneration, stroke, cancer, infectious diseases, and reproductive disorders. A substantial part of this review discusses the role of ferroptosis in the pathogenesis of reproductive disorders, such as male reproductive pathologies, including varicocele, testicular ischemia-reperfusion, cryptorchidism, oligospermia, erectile dysfunction, and testicular cancer, and female pathologies like primary ovarian insufficiency, polycystic ovary syndrome, endometriosis, ovarian cancer, and pre-eclampsia. Moreover, the interplay between ferroptosis and immune dysfunction in reproductive tract infections was highlighted. Furthermore, we evaluated current biomarkers, emerging therapeutic strategies, and key translational challenges, highlighting the promise of ferroptosis-modulating agents for novel diagnostic and therapeutic interventions in reproductive medicine and beyond.
SN - 2662-8651
ER -