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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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Korean Society for Sexual Medicine and Andrology
2025-07-01
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| Series: | The World Journal of Men's Health |
| Subjects: | |
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| Summary: | 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. |
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| ISSN: | 2287-4208 2287-4690 |