Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa
Date
Authors
BOGUEN OJEDA, RODRIGO ESTEBAN
Contreras-Mellado, Pablo
Bravo, Anita
Zambrano, Fabiola
Sánchez G., Raúl Segundo
Boguen, R.
Risopatron, Jennie
Merino, Osvaldo
Uribe, Pamela
Contreras-Mellado, Pablo
Bravo, Anita
Zambrano, Fabiola
Sánchez G., Raúl Segundo
Boguen, R.
Risopatron, Jennie
Merino, Osvaldo
Uribe, Pamela
Authors
Date
Datos de publicación:
10.5534/wjmh.240085
Keywords
Arachidonic Acid - Ferroptosis - Oxidative Stress - Sperm Function - Spermatozoa - Arachidonic Acid - Phospholipid Hydroperoxide Glutathione Peroxidase - Arachidonic Acid - Molecular Marker - Phospholipid Hydroperoxide Glutathione Peroxidase - Reactive Oxygen Metabolite - Article - Cell Death - Cell Viability - Confocal Laser Scanning Microscopy - Controlled Study - Ferroptosis - Flow Cytometry - Human - Human Cell - Lipid Peroxidation - Male - Mitochondrial Membrane Potential - Oxidative Stress - Sperm Donor - Sperm Function - Sperm Quality
Collections
Abstract
Purpose: Ferroptosis is a type of iron-dependent regulated cell death characterized by increased bioavailability of redox-active iron, loss of GPX4 antioxidant capacity, and oxidation of polyunsaturated fatty acid-containing phospholipids mediated by reactive oxygen species (ROS). The aim of this study was to evaluate the effect of oxidative stress induced by arachidonic acid (AA) on ferroptotic cell death in human spermatozoa. Materials and Methods: Spermatozoa from normozoospermic donors were exposed to AA (5, 25, and 50 ?M) for 1 hour at 37 °C, including an untreated control. Oxidative stress was confirmed by evaluation of cytosolic and mitochondrial ROS production, viability, mitochondrial membrane potential (??m) and motility. Subsequently, molecular markers of ferroptosis including iron content, levels of GPX4, SLC7A11, ACSL4, IREB2 and lipid peroxidation were evaluated. The analyses were carried out using either flow cytometry, a microplate reader or confocal laser microscopy. Results: AA-induced oxidative stress showed increased cytosolic and mitochondrial ROS production accompanied by impaired ??m, viability and motility in human spermatozoa. These results were associated with biochemical and molecular markers related to ferroptotic cell death including an increase in iron content in the form of ferrous (Fe2+) ions, SLC7A11, ACSL4, IREB2, a decrease in the level of GPX4, and an increase in the level of lipid peroxidation compared to the untreated control. Conclusions: This study revealed that AA-induced oxidative stress induces cell death with biochemical characteristics of ferroptosis in human spermatozoa, demonstrating another mechanism of alteration of sperm function induced by oxidative stress and could establish new therapeutic objectives to prevent the decrease in sperm quality mediated by oxidative stress. © 2025 Elsevier B.V., All rights reserved.
Description
Keywords
Arachidonic Acid , Ferroptosis , Oxidative Stress , Sperm Function , Spermatozoa , Arachidonic Acid , Phospholipid Hydroperoxide Glutathione Peroxidase , Arachidonic Acid , Molecular Marker , Phospholipid Hydroperoxide Glutathione Peroxidase , Reactive Oxygen Metabolite , Article , Cell Death , Cell Viability , Confocal Laser Scanning Microscopy , Controlled Study , Ferroptosis , Flow Cytometry , Human , Human Cell , Lipid Peroxidation , Male , Mitochondrial Membrane Potential , Oxidative Stress , Sperm Donor , Sperm Function , Sperm Quality
Citation
10.5534/wjmh.240085