Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa
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...
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Korean Society for Sexual Medicine and Andrology
2025-07-01
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| Series: | The World Journal of Men's Health |
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| author | Pablo Contreras-Mellado Anita Bravo Fabiola Zambrano Raúl Sánchez Rodrigo Boguen Jennie Risopatrón Osvaldo Merino Pamela Uribe |
| author_facet | Pablo Contreras-Mellado Anita Bravo Fabiola Zambrano Raúl Sánchez Rodrigo Boguen Jennie Risopatrón Osvaldo Merino Pamela Uribe |
| author_sort | Pablo Contreras-Mellado |
| collection | DOAJ |
| description | 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 μM) 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 (ΔΨm) 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
ΔΨm, 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. |
| format | Article |
| id | doaj-art-91e97cbf0177402a881d202bedbc034e |
| institution | DOAJ |
| issn | 2287-4208 2287-4690 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj-art-91e97cbf0177402a881d202bedbc034e2025-08-20T03:23:52ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-07-0143363364610.5534/wjmh.240085Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human SpermatozoaPablo Contreras-Mellado0https://orcid.org/0000-0002-5494-8177Anita Bravo1https://orcid.org/0009-0004-1909-1288Fabiola Zambrano2https://orcid.org/0000-0003-4840-0508Raúl Sánchez3https://orcid.org/0000-0003-4853-4282Rodrigo Boguen4https://orcid.org/0000-0002-0325-743XJennie Risopatrón5https://orcid.org/0000-0002-0645-3719Osvaldo Merino6https://orcid.org/0000-0001-8984-8267Pamela Uribe7https://orcid.org/0000-0001-7358-7541Center of Excellence in Translational Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco, ChileCenter of Excellence in Translational Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco, ChileCenter of Excellence in Translational Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco, ChileCenter of Excellence in Translational Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco, ChileDepartment of Diagnostic Processes and Evaluation, Faculty of Health Sciences, Universidad Católica de Temuco, Temuco, ChileCenter of Excellence of Biotechnology in Reproduction (CEBIOR), Universidad de La Frontera, Temuco, ChileCenter of Excellence of Biotechnology in Reproduction (CEBIOR), Universidad de La Frontera, Temuco, ChileCenter of Excellence in Translational Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco, ChilePurpose: 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 μM) 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 (ΔΨm) 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 ΔΨm, 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.arachidonic acidferroptosisoxidative stressspermatozoasperm function |
| spellingShingle | Pablo Contreras-Mellado Anita Bravo Fabiola Zambrano Raúl Sánchez Rodrigo Boguen Jennie Risopatrón Osvaldo Merino Pamela Uribe Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa The World Journal of Men's Health arachidonic acid ferroptosis oxidative stress spermatozoa sperm function |
| title | Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa |
| title_full | Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa |
| title_fullStr | Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa |
| title_full_unstemmed | Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa |
| title_short | Oxidative Stress Induces Changes in Molecular Markers Associated with Ferroptosis in Human Spermatozoa |
| title_sort | oxidative stress induces changes in molecular markers associated with ferroptosis in human spermatozoa |
| topic | arachidonic acid ferroptosis oxidative stress spermatozoa sperm function |
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