Oxidative Stress and Male Reproductive Health

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 4046

Special Issue Editors


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Guest Editor
School of Environmental and Life Sciences, College of Engineering, Science and Environmental Science, University of Newcastle, Callaghan, NSW 2308, Australia
Interests: oxidative stress; antioxidants; reproductive biology; fertilization; demography
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
GReD Laboratory, Université Clermont Auvergne, CNRS UMR6293, INSERM U1103, Bâtiment CRBC, 28, Place Henri Dunant, 63000 Clermont-Ferrand, France
Interests: oxidative stress and male reproductive impacts; antioxidant therapy in male fertility; oxidative DNA damage

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Guest Editor
Priority Research Centre for Reproductive Science, College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308, Australia
Interests: semen; reproductive function; oxidative stress; livestock

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Guest Editor
Priority Research Centre for Reproductive Science, Schools of Biomedical Science & Pharmacy and Environmental & Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia
Interests: male reproduction; spermatozoa; oxidative stress; DNA damage; biochemistry

Special Issue Information

Dear Colleagues,

Oxidative stress is a key factor in the aetiology of male infertility, and is heavily involved in mediating the multiple impacts of age on male reproductive function, including prostatic disease, erectile dysfunction, and the increased incidence of de novo mutations in the offspring of ageing fathers. In vitro, oxidative stress is also known to be involved in impairing the genetic and functional integrity of spermatozoa, and to impact the success of in vitro fertilization. Given the overwhelming importance of oxidative stress as a key determinant of male reproductive health, there should be a role for antioxidant therapy in the treatment of this condition. We still have a great deal to learn in this area, particularly with respect to the particular combinations of antioxidants that should be used in vivo and in vitro, the circumstances under which they should be administered, and what precautions should be taken to avoid reductive stress.

This Special Issue will be a collection of high-quality papers describing the current status of research into oxidative stress and male reproductive health. We invite papers on all aspects of this process, from its biochemical origins to its clinical consequences, particularly if they help point the way to potential therapeutic strategies, including the judicious use of antioxidant therapy. We are also keen to learn from large and small animal models the importance of this process in defining reproductive health and evaluating the potential of antioxidant treatment in vivo and in vitro.

As the Guest Editor, I invite you to contribute to the Special Issue on “Oxidative Stress and Male Reproductive Health”. Original research reports and reviews will be published online in Antioxidants.

Prof. Dr. Robert John Aitken
Prof. Dr. Joel R. Drevet
Dr. Zamira Gibb
Dr. Geoffry De Iuliis
Guest Editors

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Keywords

  • oxidative stress
  • antioxidant therapy
  • male reproductive health
  • male fertility
  • erectile dysfunction
  • prostatic disease
  • male ageing

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Published Papers (4 papers)

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Research

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19 pages, 3596 KiB  
Article
Exploring the Epigenetic Landscape of Spermatozoa: Impact of Oxidative Stress and Antioxidant Supplementation on DNA Methylation and Hydroxymethylation
by Elisa Hug, Yoan Renaud, Rachel Guiton, Mehdi Ben Sassi, Charles Marcaillou, Aron Moazamian, Parviz Gharagozloo, Joël R. Drevet and Fabrice Saez
Antioxidants 2024, 13(12), 1520; https://doi.org/10.3390/antiox13121520 (registering DOI) - 12 Dec 2024
Viewed by 958
Abstract
Reproductive success is dependent on gamete integrity, and oxidative stress alters male nuclei, meaning that no DNA repair is possible due to chromatin compaction. The composition of sperm makes it highly sensitive to reactive oxygen species (ROS) but, at the same time, ROS [...] Read more.
Reproductive success is dependent on gamete integrity, and oxidative stress alters male nuclei, meaning that no DNA repair is possible due to chromatin compaction. The composition of sperm makes it highly sensitive to reactive oxygen species (ROS) but, at the same time, ROS are needed for sperm physiology. Over the past 30 years, much attention has been paid to the consequences of oxidative stress on sperm properties and the protective effects of antioxidant formulations to help fertility. Spermatozoa also carry epigenetic marks, critical for embryo development and the health of offspring. As DNA oxidative damage may disturb the sperm epigenome, we used an established mouse model of post-testicular sperm DNA oxidation to investigate sperm DNA methylation and hydroxymethylation. We also analyzed the potential corrective effect of oral antioxidant supplementation, proven to reduce sperm DNA oxidative damage, on sperm DNA methyl/hydroxymethyl marks. We show that sperm DNA oxidation is associated with a significant increase in overall hydroxymethylation. Oral antioxidant supplementation led to unexpected mild epigenetic changes. Antioxidant supplementation should not be proposed without proper clinical evaluation as it may alter sperm epigenetic marks, leading to a risk of paternally inherited epigenetic alterations. Full article
(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)
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22 pages, 8149 KiB  
Article
Towards the Development of Novel, Point-of-Care Assays for Monitoring Different Forms of Antioxidant Activity: The RoXstaTM System
by Robert J. Aitken, Alexandra Wilkins, Natasha Harrison, Kimia Kobarfard and Sarah Lambourne
Antioxidants 2024, 13(11), 1379; https://doi.org/10.3390/antiox13111379 - 11 Nov 2024
Cited by 2 | Viewed by 1034
Abstract
(1) Background: This study set out to develop a series of simple, novel, rapid methods for assessing different forms of antioxidant activity. (2) Methods: An ABTS platform was used to engineer: (i) an electrochemical post-activation assay to assess free radical scavenging activity; (ii) [...] Read more.
(1) Background: This study set out to develop a series of simple, novel, rapid methods for assessing different forms of antioxidant activity. (2) Methods: An ABTS platform was used to engineer: (i) an electrochemical post-activation assay to assess free radical scavenging activity; (ii) an electrochemical pre-activation strategy to assesses the suppression of free radical formation; (iii) a horseradish peroxidase-mediated oxidation system to monitor hydrogen peroxide scavenging activity and (iv) a cumene peroxide-hematin system to determine the ability of samples to scavenge the mixture of organic peroxides and peroxyl and alkoxyl radicals generated in the presence of these reagents. Each assay was assessed against a panel of candidate antioxidant compounds to determine their relative activities and specificities. In addition, human semen samples were analyzed to determine how the results of these antioxidant assays correlated with semen quality. (3) Results: All 4 assays revealed dose-dependent antioxidant activity on the part of vitamin C, N-acetyl cysteine, hypotaurine, BSA, melatonin, glutathione, resveratrol and epigallocatechin gallate. The other compounds tested either completely lacked antioxidant activity or were only active in one of the assays. Using unfractionated human semen as an exemplar of biological fluids rich in antioxidants, the outputs from the individual assays were found to reflect different aspects of semen quality. When the data from all 4 assays were combined, accurate predictions were generated reflecting the importance of oxidative stress in defining semen quality as reflected by sperm count, seminal lipid aldehyde content, sperm DNA damage and free radical generation by the sperm mitochondria. (4) Conclusions: The methodologies described in this paper constitute the basis for rapid, point-of-care assessments of oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)
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Review

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17 pages, 1185 KiB  
Review
The Oxidative Stress of Human Sperm Cryopreservation
by Steven D. Fleming and Laura K. Thomson
Antioxidants 2025, 14(4), 402; https://doi.org/10.3390/antiox14040402 - 28 Mar 2025
Viewed by 492
Abstract
Due to their negligible cytoplasm and composition of the sperm plasmalemma, spermatozoa are particularly vulnerable to lipid peroxidative damage induced by reactive oxygen species (ROS). Most ROS are referred to as free radicals because they have unpaired electrons, causing them to scavenge electrons [...] Read more.
Due to their negligible cytoplasm and composition of the sperm plasmalemma, spermatozoa are particularly vulnerable to lipid peroxidative damage induced by reactive oxygen species (ROS). Most ROS are referred to as free radicals because they have unpaired electrons, causing them to scavenge electrons from atoms within tissues, resulting in oxidative damage to cellular components including cell membranes, intracellular organelles, and DNA. The potential consequences of oxidative stress include impaired sperm function, DNA fragmentation, and apoptosis. Understanding the mechanisms that mediate sperm damage during cryopreservation is key to the development of improved sperm freezing media formulations and methodology to mitigate its occurrence. Historically, elucidation of those mechanisms has proven largely elusive and is complicated by the positive role that ROS also play as messengers in redox signaling and the different pathways that mediate sperm DNA damage and apoptosis. More recently, oxidative stress has been revealed as the most likely suspect in cryopreservation-induced sperm DNA damage. This narrative review was intended to provide an in-depth analysis of the mechanisms involved and offer insight into possible improvements in sperm cryopreservation. Full article
(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)
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13 pages, 1213 KiB  
Review
Redox Regulation and Glucose Metabolism in the Stallion Spermatozoa
by Fernando J. Peña, Francisco E. Martín-Cano, Laura Becerro-Rey, Eva da Silva-Álvarez, Gemma Gaitskell-Phillips, Inés M. Aparicio, María C. Gil and Cristina Ortega-Ferrusola
Antioxidants 2025, 14(2), 225; https://doi.org/10.3390/antiox14020225 - 17 Feb 2025
Cited by 1 | Viewed by 612
Abstract
Stallion spermatozoa are cells which exhibit intense metabolic activity, where oxidative phosphorylation in the mitochondria is the primary ATP generator. However, metabolism must be viewed as a highly interconnected network of oxidation–reduction reactions that generate the energy necessary for life. An unavoidable side [...] Read more.
Stallion spermatozoa are cells which exhibit intense metabolic activity, where oxidative phosphorylation in the mitochondria is the primary ATP generator. However, metabolism must be viewed as a highly interconnected network of oxidation–reduction reactions that generate the energy necessary for life. An unavoidable side effect of metabolism is the generation of reactive oxygen species, leading to the evolution of sophisticated mechanisms to maintain redox homeostasis. In this paper, we provide an updated overview of glucose metabolism in stallion spermatozoa, highlighting recent evidence on the role of aerobic glycolysis in these cells, and the existence of an intracellular lactate shuttle that may help to explain the particular metabolism of the stallion spermatozoa in the context of their redox regulation. Full article
(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)
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