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Sperm Oxidative Stress and Male Infertility

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 6765

Special Issue Editor

Department of Histology and Developmental Biology, Faculty of Health Sciences, Pomeranian Medical University, 71-210 Szczecin, Poland
Interests: male fertility; semen analysis; sperm chromatin; sperm DNA fragmentation; oxidative stress; reactive oxygen species
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress (OS) in semen is known to be one of the most common and important factors negatively affecting both semen quality and sperm’s ability to fertilize the oocyte. Furthermore, 80% of male idiopathic infertility is associated with the generation of pathological amounts of reactive oxygen species and/or impaired antioxidant capacity, this known as Male Oxidative Stress Infertility (MOSI). Clinically, what is important is that OS in semen can be a causative factor not only in decreased membrane integrity due to the peroxidation of polyunsaturated fatty acid-rich sperm phospholipid membranes but also in sperm DNA fragmentation. Consequently, defective fertilization and embryo development can occur, both in natural and medically assisted conception. Moreover, it should be emphasized that the oxidation of sperm DNA can lead to direct modification of nitrogenous bases that can then be responsible for mutagenic or epigenetic effects likely transmitted to future generations. As such, it is essential to conduct studies focused on the etiology, epidemiology, molecular bases, and clinical consequences and therapies of OS in male infertility. We encourage the submission of original research articles and reviews, especially those that provide results at the molecular level.

Dr. Kamil Gill
Guest Editor

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Keywords

  • oxidative stress
  • antioxidant system
  • free radical scavengers
  • sperm DNA oxidation
  • sperm DNA fragmentatio
  • antioxidant therapy
  • male infertility
  • male oxidative stress infertility

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Published Papers (4 papers)

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Research

14 pages, 1148 KB  
Article
Seminal Redox Improvement and Sperm Proteome Remodeling After Deprox-HP Nutraceutical Supplementation in Male Accessory Gland Inflammation: A Pilot Study
by Fiorella Di Nicuolo, Alessandro Oliva, Emanuele Pierpaolo Vodola, Michela Cicchinelli, Federica Iavarone, Carla Di Nardo, Edoardo Vergani, Paola Girardi, Francesca Mancini, Alfredo Pontecorvi, Andrea Urbani, Silvia Baroni, Domenico Milardi and Emanuela Teveroni
Int. J. Mol. Sci. 2026, 27(5), 2498; https://doi.org/10.3390/ijms27052498 - 9 Mar 2026
Viewed by 298
Abstract
Male accessory gland inflammation (MAGI) can impair male fertility through inflammation-driven oxidative stress and direct sperm damage; nutraceutical approaches may be useful when antibiotics are not indicated. Here, we evaluated a 3-month treatment with a Graminex™-based dietary supplement (Deprox-HP) in twenty MAGI patients [...] Read more.
Male accessory gland inflammation (MAGI) can impair male fertility through inflammation-driven oxidative stress and direct sperm damage; nutraceutical approaches may be useful when antibiotics are not indicated. Here, we evaluated a 3-month treatment with a Graminex™-based dietary supplement (Deprox-HP) in twenty MAGI patients integrating conventional semen analysis and oxidative stress assessment with sperm proteomics before and after therapy. After treatment, total and progressive sperm motility increased significantly, whereas sperm concentration and sperm morphology showed a non-significant upward trend. Sperm lipid peroxidation decreased markedly, while the antioxidant capacity showed a non-significant increase. Analysis of the sperm proteome demonstrated a clear PRE–POST clustering, consistent with treatment-associated remodeling. POST samples showed upregulation of proteins linked to sperm motility, redox homeostasis, mitochondrial metabolism and membrane remodeling. Two pregnancies occurred during the treatment period; in both cases, lipid peroxidation decreased along with an increase of morphologically typical spermatozoa, and sperm proteomics showed a concordant post-treatment shift enriched in flagellar and mitochondrial respiratory/redox compartments. Moreover, we found a selective enrichment POST treatment in these two patients of TEX50, a crucial protein involved in acrosome/head-stability during epididymal transit. Overall, Deprox-HP was associated with reduced oxidative membrane damage and a coordinated sperm proteomic shift consistent with improved motility. Full article
(This article belongs to the Special Issue Sperm Oxidative Stress and Male Infertility)
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14 pages, 1821 KB  
Article
Antioxidant Enzyme Activity and mRNA Expression in the Reproductive Tissues of Male European Red Deer (Cervus elaphus elaphus)
by Nicoletta M. Neuman, Przemysław Gilun, Magdalena Koziorowska-Gilun, Paweł Janiszewski and Anna Dziekońska
Int. J. Mol. Sci. 2025, 26(15), 7221; https://doi.org/10.3390/ijms26157221 - 25 Jul 2025
Cited by 1 | Viewed by 997
Abstract
The aim of this study was to analyze the influence of season (rut and non-rut) on the antioxidant status of selected reproductive tissues in male European red deer (Cervus elaphus elaphus). Tissue samples were collected post mortem from the testes and [...] Read more.
The aim of this study was to analyze the influence of season (rut and non-rut) on the antioxidant status of selected reproductive tissues in male European red deer (Cervus elaphus elaphus). Tissue samples were collected post mortem from the testes and epididymides (caput, corpus, and cauda) of 24 animals. The activity of antioxidant enzymes (superoxide dismutase—SOD, glutathione peroxidase—GPx, and catalase—CAT) and the mRNA expression of SOD1, SOD2, SOD3, GPx4, GPx5, and CAT were examined. In addition, these proteins were identified by western blot. ANOVA revealed that season, type of tissue, and the interaction between these factors significantly (p ≤ 0.05) influenced the activity and mRNA expression of the analyzed enzymes. The activity of SOD and GPx peaked in the corpus epididymis in the rut season and in the caput epididymis in the non-rut season. Regardless of season, the relative abundances of GPx4, SOD1, SOD2, and SOD3 mRNA were highest in the testis, and GPx5 mRNA—in the caput epididymis. The activity of SOD and CAT was significantly higher during the non-rut season compared with the rut season, but only in the caput epididymis. This study demonstrated that the activity of antioxidant enzymes and the relative mRNA expression varies across tissues and seasons to provide the reproductive system of European red deer with the required antioxidant protection. Further research is needed to expand our understanding of the antioxidant defense system in the reproductive tract of European red deer. Full article
(This article belongs to the Special Issue Sperm Oxidative Stress and Male Infertility)
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20 pages, 1476 KB  
Article
Influence of Body Mass Index (BMI) and Waist–Hip Ratio (WHR) on Selected Semen Parameters
by Kamil Gill, Monika Fraczek, Maciej Kurpisz and Małgorzata Piasecka
Int. J. Mol. Sci. 2025, 26(9), 4089; https://doi.org/10.3390/ijms26094089 - 25 Apr 2025
Cited by 3 | Viewed by 2688
Abstract
Because male obesity may result in reproductive failure, we aimed to examine the possible links among body mass index (BMI), the waist–hip ratio (WHR), and basic semen parameters, the oxidation–reduction potential of semen, the total antioxidant capacity of seminal plasma, the ability of [...] Read more.
Because male obesity may result in reproductive failure, we aimed to examine the possible links among body mass index (BMI), the waist–hip ratio (WHR), and basic semen parameters, the oxidation–reduction potential of semen, the total antioxidant capacity of seminal plasma, the ability of sperm to bind hyaluronic acid, and sperm DNA fragmentation (SDF). This study was performed on semen (n = 543) collected from volunteers classified as follows: normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2), obese (BMI ≥ 30.0 kg/m2), with a normal WHR (<1) or abnormal WHR (≥1). No significant differences in standard semen parameters were found between men with a normal BMI and those with overweight/obesity. However, compared with overweight men, obese men had a higher SDF index prevalence and risk for an SDF index > 20%. Compared with men with WHR < 1, those with WHR ≥ 1 had significantly lower sperm motility, morphology, and vitality and an increased SDF index, prevalence and risk for an SDF index > 20%. In conclusion, abnormal WHR had a greater negative impact on conventional semen parameters than abnormal BMI. Both BMI ≥ 30.0 and WHR ≥ 1 negatively influenced sperm chromatin integrity only. Obesity is a potential risk factor for sperm DNA damage. Full article
(This article belongs to the Special Issue Sperm Oxidative Stress and Male Infertility)
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20 pages, 3133 KB  
Article
Proteomic Alterations and Oxidative Stress in Seminal Plasma of Nellore Bulls Under Sexual Rest
by Ekaette Chris Udoekong, Camilo Jose Ramirez-Lopez, Denise Silva Okano, Edvaldo Barros, Pedro Marcus Pereira Vidigal, Iara Magalhães Ribeiro, Renner Philipe Rodrigues Carvalho, Mariana Machado-Neves, José Domingos Guimarães and Simone Eliza Facioni Guimarães
Int. J. Mol. Sci. 2025, 26(6), 2457; https://doi.org/10.3390/ijms26062457 - 10 Mar 2025
Cited by 1 | Viewed by 1706
Abstract
Sexual rest (SR) in bulls leads to the accumulation of senescent spermatozoa in the extragonadal reserves, potentially affecting semen quality and reproductive efficiency. Therefore, this study aimed to investigate the impact of SR on the seminal plasma proteome and oxidative status of Nellore [...] Read more.
Sexual rest (SR) in bulls leads to the accumulation of senescent spermatozoa in the extragonadal reserves, potentially affecting semen quality and reproductive efficiency. Therefore, this study aimed to investigate the impact of SR on the seminal plasma proteome and oxidative status of Nellore bulls. Six adult bulls were subjected to 195 days of SR and sequential semen collections using the electroejaculation method. The ejaculates were analyzed to assess sperm quality. Seminal plasma from the first and last ejaculates was evaluated for oxidative status and proteomic profile using LC-MS. The results revealed significant improvements in sperm motility, vigor, and antioxidant enzyme activity (superoxide dismutase and catalase) in the last ejaculate compared to the first. Conversely, higher levels of oxidative markers, such as malondialdehyde and carbonyl proteins, were observed in the first ejaculate. Proteomic analysis identified 156 proteins, with 28 differentially abundant between ejaculates. The first ejaculate showed a higher abundance of proteins linked to acrosomal exocytosis and energy metabolism, while proteins associated with sperm motility and immune modulation were elevated in the last ejaculate. These findings suggest that SR induces oxidative stress and proteomic alterations in seminal plasma, negatively affecting sperm quality, emphasizing the need for strategic reproductive management in bulls. Full article
(This article belongs to the Special Issue Sperm Oxidative Stress and Male Infertility)
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