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Antioxidants
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Oxidative Stress, Antioxidants and Male Reproduction
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Oxidative Stress, Antioxidants and Male Reproduction

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: closed (30 April 2022) | Viewed by 66000

Special Issue Editors

Prof. Dr. Giulia Collodel

E-Mail Website
Guest Editor
Department of Molecular & Developmental Medicine, Università degli Studi di Siena, 53100 Siena, Italy
Interests: human sperm; male infertility; immunohistochemistry; transmission electron microscopy; antioxidant; oxidative stress; fatty acids
Dr. Elena Moretti

E-Mail Website
Co-Guest Editor
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
Interests: human spermatozoa; male infertility; oxidative stress in seminal plasma and in spermatozoa; human sperm morphology; spermatoza as a cell model in in vitro experiments
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress (OS) results from an imbalance between the production of radical oxygen species and antioxidant defenses, and it is believed to play a central role in pathogenesis and clinical progression of male infertility. It has been known that PUFAs represent the main target of the free radical insult, leading to the oxidative lipid deterioration causing alterations in sperm functional characteristics. On account of this, OS is associated with the matters of human and animal reproduction. Traditionally, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and isoprostanes have been used as diagnostic markers for oxidative damage to lipid in sperm membranes. Dietary administration of antioxidants may be a therapeutic option, and animals could be suitable models for the study of the effects of these supplementations in the spermatogenetic process.

Oxidative stress and sperm

Antioxidants and spermatogenesis

Antioxidant effect on male infertility

Oxidative stress and male infertility in animal model

Antioxidant dietary model in male infertility

Prof. Giulia Collodel
Prof. Elena Moretti
Guest Editors

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Keywords

  • spermatozoa
  • oxidative stress
  • lipid peroxidation
  • antioxidants
  • dietary antioxidants

Published Papers (18 papers)

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14 pages, 877 KiB  
Article
High-Risk HPV with Multiple Infections Promotes CYP2E1, Lipoperoxidation and Pro-Inflammatory Cytokines in Semen of Asymptomatic Infertile Men
by Elvia Pérez-Soto, María Olivia Medel-Flores, Eduardo Fernández-Martínez, Rigoberto Oros-Pantoja, José Cruz Miranda-Covarrubias and Virginia Sánchez-Monroy
Antioxidants 2022, 11(6), 1051; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061051 - 26 May 2022
Cited by 3 | Viewed by 1931
Abstract
High-risk human papillomavirus (HR-HPV) infection, followed by chronic inflammation and oxidative stress, is a major risk factor of male infertility. In this study, we explored the potential impact of high-risk (HR) HPV genotypes in single infection (SI) and multiple infections (MI) that promote [...] Read more.
High-risk human papillomavirus (HR-HPV) infection, followed by chronic inflammation and oxidative stress, is a major risk factor of male infertility. In this study, we explored the potential impact of high-risk (HR) HPV genotypes in single infection (SI) and multiple infections (MI) that promote CYP2E1 expression, oxidative damage and pro-inflammatory cytokines, possibly contributing to sperm damage and male infertility. Semen samples from 101 infertile military men were studied. We analyzed seminal parameters, namely, HPV genotyping, cytochrome P450 2E1 (CYP2E1), oxidative stress biomarkers (total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD)), lipid peroxidation (LPO), 8-hydroxiguanosine (8-OHdG) and pro-inflammatory cytokines (IFN-γ, IL-1β, IL-4, IL-6 and IL-8). Eighty-one men (80.2%, 81/101) were positive for HPV infection, and MI-HR-HPV was higher than SI-HR-HPV (63% vs. 37%). HPV-52 was the most frequently detected type (18.5%), followed by HPV-33 (11.1%), and the most frequent combination of genotypes detected was HPV-33,52 (11.1%), followed by HPV-18,31 (6.2%). The group with infected samples presented lower normal morphology and antioxidant levels compared to non-infected samples. In concordance, the infected group showed high levels of LPO, IFN-γ, IL-1β, IL-4 and IL-6 and downregulation of CAT and SOD enzymes. Interestingly, changes in motility B, low levels of TAC, overexpression of CYP2E1, LPO and IL-8 levels were higher in MI-HR-HPV than SI-HR-HPV, suggesting that HPV infection promotes a chronic inflammatory process and a toxic and oxidative microenvironment, which increases with MI-HPV infections. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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14 pages, 1947 KiB  
Article
Andrological Aspects of Exercise: Moderate Swimming Protects against Isoproterenol Induced Testis and Semen Abnormalities in Rats
by Péter Osváth, Miklós Szűcs, Denise Börzsei, Renáta Szabó, Zelma Nadin Lesi, Zsolt Turcsán, Médea Veszelka, Judith Sebestyén, Béla Juhász, Dániel Priksz, Csaba Varga and Anikó Pósa
Antioxidants 2022, 11(3), 436; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11030436 - 22 Feb 2022
Cited by 3 | Viewed by 1697
Abstract
The development and progression of male infertility are closely linked to a sedentary lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the protective effects of moderate swimming exercise on the male reproductive system in isoproterenol-treated rats. Male [...] Read more.
The development and progression of male infertility are closely linked to a sedentary lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the protective effects of moderate swimming exercise on the male reproductive system in isoproterenol-treated rats. Male Wistar rats were divided into five groups as follows: (1) non-interventional controls (CTRL), (2) isoproterenol-treated (ISO), (3) pre-treatment swimming training + ISO (PRE + ISO), (4) ISO + post-treatment swimming training (ISO+POST), (5) pre-treatment swimming training + ISO + post-treatment swimming training (PRE + ISO + POST) groups. Testicular oxidative stress was induced by ISO injection (1.0 mg/kg). Rats in the pre- or post-training groups were trained five days a week. At the end of the experimental period, serum testosterone levels, sperms’ hyaluronan binding, and total glutathione (GSH) content, as well as myeloperoxidase activity (MPO), TNF alpha and IL6 concentrations in the testis and semen, were measured. Serum testosterone levels, sperms’ hyaluronan binding, and GSH content were found to be significantly reduced, while MPO, TNF alpha and IL6 concentrations in the testis and semen were elevated after the ISO treatment compared to the CTRL group. Moderate-intensity swimming exercise effectively alleviated the negative effects of high oxidative stress. Our findings provide the first evidence that moderate-intensity swimming exercise confers sustained protection from isoproterenol-induced adverse effects on testicular inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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22 pages, 2955 KiB  
Article
Impact of Seminal Plasma Antioxidants on Donkey Sperm Cryotolerance
by Jaime Catalán, Iván Yánez-Ortiz, Asta Tvarijonaviciute, Luis Guillermo González-Arostegui, Camila P. Rubio, Marc Yeste, Jordi Miró and Isabel Barranco
Antioxidants 2022, 11(2), 417; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020417 - 18 Feb 2022
Cited by 8 | Viewed by 2554
Abstract
This study investigated whether the activities of the antioxidant components of donkey seminal plasma (SP)—both enzymatic (superoxide dismutase (SOD), catalase-like (CAT), glutathione peroxidase-like (GPX), and paraoxonase type 1 (PON1)) and non-enzymatic (measured in terms of total thiol, copper-reducing antioxidant capacity (CUPRAC), ferric-reducing ability [...] Read more.
This study investigated whether the activities of the antioxidant components of donkey seminal plasma (SP)—both enzymatic (superoxide dismutase (SOD), catalase-like (CAT), glutathione peroxidase-like (GPX), and paraoxonase type 1 (PON1)) and non-enzymatic (measured in terms of total thiol, copper-reducing antioxidant capacity (CUPRAC), ferric-reducing ability of plasma (FRAP), and Trolox equivalent antioxidant capacity (TEAC))—and oxidative stress index (OSI) are related to sperm cryotolerance. For this purpose, 15 ejaculates from jackasses (one per individual) were collected and split into two aliquots. The first one was used for measuring the activities levels of enzymatic and non-enzymatic antioxidants and OSI in SP, whereas the other aliquot was cryopreserved. Before cryopreservation, sperm quality parameters (concentration, motility, and viability) were evaluated. After thawing, sperm motility, plasma membrane integrity, lipid disorder, mitochondrial membrane potential, reactive oxygen species (ROS), and calcium intracellular levels were also determined. Based on the percentages of total motility (TM) and of sperm with an intact plasma membrane (SYBR14+/PI−) after thawing, samples were classified as good-freezability (GFE) or poor-freezability (PFE) ejaculates through cluster analyses. The SP activity levels of enzymatic (SOD and PON1) and non-enzymatic antioxidants (CUPRAC, FRAP, and TEAC) were higher (p < 0.05) in GFE than in PFE, whereas SP-OSI was higher (p < 0.05) in PFE than in GFE. In addition, the activity levels of SOD, PON1, GPX, CUPRAC, FRAP, and TEAC were positively (p < 0.05) related to post-thaw sperm motility and plasma membrane integrity and negatively to intracellular ROS levels. The SP-OSI was negatively correlated (p < 0.05) to post-thaw sperm quality parameters and positively to intracellular ROS levels. It can thus be concluded that donkey SP antioxidants are related to sperm cryotolerance and that measurements of antioxidants PON1, SOD, CUPRAC, FRAP, and TEAC, as well as SP-OSI, could be used as markers of sperm cryotolerance. Further research addressing the relationship of these antioxidants and SP-OSI with sperm cryotolerance and their potential use as freezing markers is warranted. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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17 pages, 2246 KiB  
Article
Peroxiredoxin 6 Peroxidase and Ca2+-Independent Phospholipase A2 Activities Are Essential to Support Male-Mouse Fertility
by Edrian Bumanlag, Eleonora Scarlata and Cristian O’Flaherty
Antioxidants 2022, 11(2), 226; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020226 - 25 Jan 2022
Cited by 12 | Viewed by 2395
Abstract
Human infertility is an important health problem that affects one in six couples worldwide. Half of these cases are due to male infertility. Oxidative stress is a common culprit of male infertility, promoting lipid peroxidation and the oxidation of proteins and DNA in [...] Read more.
Human infertility is an important health problem that affects one in six couples worldwide. Half of these cases are due to male infertility. Oxidative stress is a common culprit of male infertility, promoting lipid peroxidation and the oxidation of proteins and DNA in spermatozoa, thereby impairing motility, capacitation and fertilization. Peroxiredoxin 6 (PRDX6) possesses peroxidase and Ca2+-independent-phospholipase-A2 (iPLA2) activities that scavenge ROS and repair oxidized sperm membranes, respectively. PRDX6 protects spermatozoa against oxidative stress. Infertile men’s spermatozoa have impaired motility, elevated lipid peroxidation levels and DNA damage due to low PRDX6 levels. A lack of PRDX6 is associated with male-mouse infertility. Here, we determined the impact of the absence of PRDX6 peroxidase or iPLA2 activities on male-mouse fertility. Two-month-old male C57Bl6/J (wild-type), Prdx6−/−, C47S and D140A knock-in (peroxidase- and iPLA2-deficient, respectively) male mice were challenged with an in vivo oxidative stress triggered by tert-butyl hydroperoxide (t-BHP). C47S and D140A males produced smaller litters compared to wild-type controls. The t-BHP treatment promoted a lower number of pups, high levels of lipid peroxidation, tyrosine nitration, and DNA oxidation in all mutant spermatozoa compared to wild-type controls. All mutant spermatozoa had impaired capacitation and motility. In summary, both PRDX6 peroxidase and iPLA2 activities are essential to support male-mouse fertility. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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14 pages, 1935 KiB  
Article
Fatty Acid Oxidation and Pro-Resolving Lipid Mediators Are Related to Male Infertility
by Cinzia Signorini, Elena Moretti, Daria Noto, Lucia Micheli, Rosetta Ponchia and Giulia Collodel
Antioxidants 2022, 11(1), 107; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010107 - 02 Jan 2022
Cited by 10 | Viewed by 1887
Abstract
Specialized pro-resolving lipid mediators regulate the resolution of acute inflammation. They are formed by enzymatic oxygenation of polyunsaturated fatty acids and are divided into families including lipoxins, resolvins, protectins, and maresins. Resolvin D1 (RvD1), produced by docosahexaenoic acid, exerts anti-inflammatory and pro-resolving activities. [...] Read more.
Specialized pro-resolving lipid mediators regulate the resolution of acute inflammation. They are formed by enzymatic oxygenation of polyunsaturated fatty acids and are divided into families including lipoxins, resolvins, protectins, and maresins. Resolvin D1 (RvD1), produced by docosahexaenoic acid, exerts anti-inflammatory and pro-resolving activities. This research aimed to investigate the implication of seminal RvD1 in human infertility. Infertile patients (n° 67) were grouped based on pathological reproductive conditions as idiopathic infertility, varicocele, and leukocytospermia; the fourth group was composed of fertile men (n° 18). Sperm characteristics were evaluated by light microscopy (WHO guidelines) and by transmission electron microscopy (TEM). The seminal levels of RvD1 and F2-isoprostane (F2-IsoPs) were dosed. In twenty men (6 fertile men, 8 with varicocele, 6 with leukocytospermia) seminal phospholipase A2, iron, cholesterol, transferrin, estradiol, ferritin, testosterone, and sperm membrane fatty acids were detected. The results indicated that: (i) RvD1 amount was positively correlated with F2-IsoPs and reduced sperm quality; (ii) RvD1 levels were significantly higher in patients with leukocytospermia, varicocele, and idiopathic infertility compared to fertile men; (iii) RvD1 increased along with other markers of oxidative stress and inflammation as fatty acids content and clinical biomarkers. This study suggests a panel of inflammatory markers and lipid mediators for a diagnosis of inflammatory status and a subsequent appropriate therapeutic approach. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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18 pages, 2451 KiB  
Article
Extracellular Reactive Oxygen Species (ROS) Production in Fresh Donkey Sperm Exposed to Reductive Stress, Oxidative Stress and NETosis
by Iván Yánez-Ortiz, Jaime Catalán, Yentel Mateo-Otero, Marta Dordas-Perpinyà, Sabrina Gacem, Natalia Yeste, Anna Bassols, Marc Yeste and Jordi Miró
Antioxidants 2021, 10(9), 1367; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10091367 - 27 Aug 2021
Cited by 11 | Viewed by 2828
Abstract
Jenny shows a large endometrial reaction after semen influx to the uterus with a large amount of polymorphonuclear neutrophils (PMN) migrating into the uterine lumen. PMN act as a sperm selection mechanism through phagocytosis and NETosis (DNA extrudes and, together with proteins, trap [...] Read more.
Jenny shows a large endometrial reaction after semen influx to the uterus with a large amount of polymorphonuclear neutrophils (PMN) migrating into the uterine lumen. PMN act as a sperm selection mechanism through phagocytosis and NETosis (DNA extrudes and, together with proteins, trap spermatozoa). While a reduced percentage of spermatozoa are phagocytosed by PMN, most are found to be attached to neutrophil extracellular traps (NETs). This selection process together with sperm metabolism produces a large amount of reactive oxygen species (ROS) that influence the reproductive success. The present study aimed to determine the extracellular ROS production in both sperm and PMN. With this purpose, (1) donkey sperm were exposed to reductive and oxidative stresses, through adding different concentrations of reduced glutathione (GSH) and hydrogen peroxide (H2O2), respectively; and (2) PMN were subjected to NETosis in the presence of the whole semen, sperm, seminal plasma (SP) or other activators such as formyl-methionyl-leucyl-phenylalanine (FMLP). Extracellular ROS production (measured as H2O2 levels) was determined with the Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Donkey sperm showed more resilience to oxidative stress than to the reductive one, and GSH treatments led to greater H2O2 extracellular production. Moreover, not only did SP appear to be the main inducer of NETosis in PMN, but it was also able to maintain the extracellular H2O2 levels produced by sperm and NETosis. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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15 pages, 1547 KiB  
Article
Protective Effect of Chlorogenic Acid on Human Sperm: In Vitro Studies and Frozen–Thawed Protocol
by Daria Noto, Giulia Collodel, Daniela Cerretani, Cinzia Signorini, Laura Gambera, Andrea Menchiari and Elena Moretti
Antioxidants 2021, 10(5), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10050744 - 07 May 2021
Cited by 11 | Viewed by 2896
Abstract
The study evaluated the chlorogenic acid (CGA) antioxidant potential on oxidative stress (OS) induced in vitro in human spermatozoa and during cryopreservation procedure. Swim-up selected spermatozoa were treated with 100 µM CGA, 100 µM H2O2 to induce lipid peroxidation (LPO), [...] Read more.
The study evaluated the chlorogenic acid (CGA) antioxidant potential on oxidative stress (OS) induced in vitro in human spermatozoa and during cryopreservation procedure. Swim-up selected spermatozoa were treated with 100 µM CGA, 100 µM H2O2 to induce lipid peroxidation (LPO), and with both compounds and the effects on mitochondrial membrane potential (MMP) by JC-1, DNA integrity by acridine orange (AO), and sperm ultrastructure by transmission electron microscopy (TEM), were evaluated. CGA antioxidant activity was assessed by measuring malondialdehyde (MDA) and F2-isoprostanes (F2-IsoPs) in the media. The CGA protective activity and the immunolocalization of Phospho-AMPKα (Thr172) were explored in frozen-thawed sperm. CGA was not toxic for sperm motility, DNA integrity and MMP. The increase in MDA (p < 0.05) and F2-IsoPs (p < 0.001), DNA damage (p < 0.01) and low MMP (p < 0.01) levels after H2O2 treatment were reduced in presence of CGA as well as the percentage of broken plasma membranes (p < 0.01) and altered acrosomes (p < 0.01) detected by TEM. Treated frozen-thawed spermatozoa showed increased sperm motility (p < 0.01), DNA integrity (p < 0.01), MMP (p < 0.01), reduced MDA (p < 0.01) and increased sperm percentage with Phospho-AMPKα labelling in the head (p < 0.001). CGA can be used to supplement culture media during semen handling and cryopreservation where OS is exacerbated. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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21 pages, 3792 KiB  
Article
Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model
by Simona Mattioli, Giulia Collodel, Cinzia Signorini, Elisa Cotozzolo, Daria Noto, Daniela Cerretani, Lucia Micheli, Anna Ida Fiaschi, Gabriele Brecchia, Laura Menchetti, Elena Moretti, Camille Oger, Claudio De Felice and Cesare Castellini
Antioxidants 2021, 10(5), 681; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10050681 - 27 Apr 2021
Cited by 12 | Viewed by 2591
Abstract
Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, [...] Read more.
Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (n = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.5% fish oil + 200 mg/kg vitamin E. Antioxidants (enzymatic and non-enzymatic), oxidative status (malondialdehyde and isoprostanoids), and n-3 and n-6 PUFAs of tissues were analysed. A chain mechanism of oxidant/antioxidant molecules, which largely depended on the particular PUFA composition, was delineated in the different organs. The liver showed an oxidant/antioxidant profile and lipid pathways widely modulated by PUFA and vitamin E administration; on the other hand, the testis’ oxidative profile rather than its lipid profile seemed to be particularly affected, an outcome opposite to that of the brain (modulation operated by dietary PUFA). Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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17 pages, 2383 KiB  
Article
Mechanistic Insight into the Regulation of Lipoxygenase-Driven Lipid Peroxidation Events in Human Spermatozoa and Their Impact on Male Fertility
by Jessica L. H. Walters, Amanda L. Anderson, Sarah J. Martins da Silva, R. John Aitken, Geoffry N. De Iuliis, Jessie M. Sutherland, Brett Nixon and Elizabeth G. Bromfield
Antioxidants 2021, 10(1), 43; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010043 - 31 Dec 2020
Cited by 9 | Viewed by 2727
Abstract
A prevalent cause of sperm dysfunction in male infertility patients is the overproduction of reactive oxygen species, an attendant increase in lipid peroxidation and the production of cytotoxic reactive carbonyl species such as 4-hydroxynonenal. Our previous studies have implicated arachidonate 15-lipoxygenase (ALOX15) in [...] Read more.
A prevalent cause of sperm dysfunction in male infertility patients is the overproduction of reactive oxygen species, an attendant increase in lipid peroxidation and the production of cytotoxic reactive carbonyl species such as 4-hydroxynonenal. Our previous studies have implicated arachidonate 15-lipoxygenase (ALOX15) in the production of 4-hydroxynonenal in developing germ cells. Here, we have aimed to develop a further mechanistic understanding of the lipoxygenase-lipid peroxidation pathway in human spermatozoa. Through pharmacological inhibition studies, we identified a protective role for phospholipase enzymes in the liberation of peroxidised polyunsaturated fatty acids from the human sperm membrane. Our results also revealed that arachidonic acid, linoleic acid and docosahexanoic acid are key polyunsaturated fatty acid substrates for ALOX15. Upon examination of ALOX15 in the spermatozoa of infertile patients compared to their normozoospermic counterparts, we observed significantly elevated levels of ALOX15 protein abundance in the infertile population and an increase in 4-hydroxynonenal adducts. Collectively, these data confirm the involvement of ALOX15 in the oxidative stress cascade of human spermatozoa and support the notion that increased ALOX15 abundance in sperm cells may accentuate membrane lipid peroxidation and cellular dysfunction, ultimately contributing to male infertility. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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19 pages, 5912 KiB  
Article
Insight Study on the Comparison between Zinc Oxide Nanoparticles and Its Bulk Impact on Reproductive Performance, Antioxidant Levels, Gene Expression, and Histopathology of Testes in Male Rats
by Amira A. Goma, Hossam G. Tohamy, Sara E. El-Kazaz, Mohamed M. Soliman, Mustafa Shukry, Ahmed M. Elgazzar and Rashed R. Rashed
Antioxidants 2021, 10(1), 41; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010041 - 31 Dec 2020
Cited by 7 | Viewed by 3049
Abstract
Background: Despite the beneficial effects of zinc oxide nanoparticles (ZnONPs) on different biomedical applications, including their antioxidant and anti-inflammatory ones, it might have cytotoxic and genotoxic impacts on the male reproductive system. Objective: The current study compares the effect of zinc oxide nanoparticles [...] Read more.
Background: Despite the beneficial effects of zinc oxide nanoparticles (ZnONPs) on different biomedical applications, including their antioxidant and anti-inflammatory ones, it might have cytotoxic and genotoxic impacts on the male reproductive system. Objective: The current study compares the effect of zinc oxide nanoparticles and their bulk form, at different doses, on male rats’ reproductive performance, testicular antioxidants, gene expression, and histopathology. Materials and Methods: Thirty male rats were randomly allocated equally in five groups. The control one was injected with Tween 80 (10%). The zinc oxide nanoparticle (ZnONP) groups received ZnONPs < 50 nm, specifically, 5 mg/kg (ZnONP-1) and 10 mg/kg (ZnONP-2). The bulk zinc oxide (BZnO) groups were administered 5 mg/kg (BZnO-1) and 10 mg/kg (BZnO-2), correspondingly. Rats were injected intraperitoneally with the respected materials, twice/week for eight consecutive weeks. Finally, the male rats’ sexual behavior and their pup’s performance were determined in a monogamous mating system. Rats were then anesthetized and sacrificed for semen characteristics evaluation and tissue collection for antioxidant and hormones analysis, gene expression, and histopathological examination. Results: It was shown that ZnONP-1 improved sexual behavior, semen characteristics, and pup’s performance compared to its bulk form. Similarly, the testicular antioxidants activity, glutathione (GSH), and superoxide dismutase (SOD) increased with a decrease in the malonaldehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. It also improves the reproductive hormone levels and mRNA expression of different steroidogenesis-associated genes and anti-apoptotic genes. Conclusion: It can be concluded that zinc oxide nanoparticles, administered at 5 mg/kg, had the most beneficial effect on male reproductive performance, while 10 mg/kg could have a detrimental effect. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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17 pages, 2755 KiB  
Article
Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats
by Yasmina M. Abd El-Hakim, Amany Abdel-Rahman Mohamed, Safaa I. Khater, Ahmed Hamed Arisha, Mohamed M. M. Metwally, Mohamed A. Nassan and Manal Ewaiss Hassan
Antioxidants 2021, 10(1), 17; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010017 - 27 Dec 2020
Cited by 38 | Viewed by 3977
Abstract
Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ [...] Read more.
Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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16 pages, 2161 KiB  
Article
The Modulatory Role of Vitamin C in Boldenone Undecylenate Induced Testicular Oxidative Damage and Androgen Receptor Dysregulation in Adult Male Rats
by Amany Behairy, Nabela I. El-Sharkawy, Taghred M. Saber, Mohamed Mohamed Soliman, Mohamed M.M. Metwally, Ghada I. Abd El-Rahman, Yasmina M. Abd-Elhakim and Maha M. El Deib
Antioxidants 2020, 9(11), 1053; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111053 - 28 Oct 2020
Cited by 23 | Viewed by 5942
Abstract
Background: This study explored the effect of vitamin C (Vit-C) administration on the reproductive function of adult male Wistar rats injected with boldenone undecylenate (BOL). Methods: Rats were randomly assigned into control, vehicle control, Vit-C (120 mg/kg b.wt./day, orally), BOL (received 5 mg/kg [...] Read more.
Background: This study explored the effect of vitamin C (Vit-C) administration on the reproductive function of adult male Wistar rats injected with boldenone undecylenate (BOL). Methods: Rats were randomly assigned into control, vehicle control, Vit-C (120 mg/kg b.wt./day, orally), BOL (received 5 mg/kg b.wt./week, IM) and BOL+Vit-C-treated groups. After eight weeks, hormonal assay, semen evaluation, testicular enzymes, and antioxidants biomarkers were assessed. Besides, the histopathological and immunohistochemical investigations of the androgen receptor (AR) expression were performed. Results: The results revealed that serum testosterone, acid phosphatase, sorbitol dehydrogenase, sperm abnormalities, and testicular malondialdehyde were significantly incremented in the BOL-treated group. Testicular weight, sperm count, and sperm motility together with serum levels of luteinizing hormone, follicle-stimulating hormone, and estradiol, and testicular testosterone, catalase, superoxide dismutase, and reduced glutathione showed a significant decrease following BOL treatment. Besides, the AR immunoreactivity was significantly decreased in testicular tissues. Vit-C co-administration with BOL significantly relieved the BOL-induced sperm abnormalities, reduced sperm motility, testicular enzyme leakage, and oxidative damage. However, Vit-C could rescue neither BOL-induced hormonal disturbances nor AR down-regulation. Conclusions: The results provide further insight into the mechanisms of BOL-induced reproductive dysfunction and its partial recovery by Vit-C. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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14 pages, 1773 KiB  
Article
Exploring Seminal Plasma GSTM3 as a Quality and In Vivo Fertility Biomarker in Pigs—Relationship with Sperm Morphology
by Marc Llavanera, Ariadna Delgado-Bermúdez, Yentel Mateo-Otero, Lorena Padilla, Xavier Romeu, Jordi Roca, Isabel Barranco and Marc Yeste
Antioxidants 2020, 9(8), 741; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9080741 - 12 Aug 2020
Cited by 9 | Viewed by 2883
Abstract
Glutathione S-transferases Mu 3 (GSTM3) is an essential antioxidant enzyme whose presence in sperm has recently been related to sperm cryotolerance, quality and fertility. However, its role in seminal plasma (SP) as a predictor of the same sperm parameters has never been investigated. [...] Read more.
Glutathione S-transferases Mu 3 (GSTM3) is an essential antioxidant enzyme whose presence in sperm has recently been related to sperm cryotolerance, quality and fertility. However, its role in seminal plasma (SP) as a predictor of the same sperm parameters has never been investigated. Herein, cell biology and proteomic approaches were performed to explore the presence, origin and role of SP-GSTM3 as a sperm quality and in vivo fertility biomarker. GSTM3 in SP was quantified using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit specific for Sus scrofa, whereas the presence of GSTM3 in testis, epididymis and accessory sex glands was assessed through immunoblotting analysis. Sperm quality and functionality parameters were evaluated in semen samples at 0 and 72 h of liquid-storage, whereas fertility parameters were recorded over a 12-months as farrowing rate and litter size. The presence and concentration of GSTM3 in SP was established for the first time in mammalian species, predominantly synthesized in the epididymis. The present study also evidenced a relationship between SP-GSTM3 and sperm morphology and suggested it is involved in epididymal maturation rather than in ejaculated sperm physiology. Finally, the data reported herein ruled out the role of this antioxidant enzyme as a quality and in vivo fertility biomarker of pig sperm. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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13 pages, 4709 KiB  
Article
A Novel Combination of γ-Tocopherol-Rich Mixture of Tocopherols and Ascorbic Acid Restores Fertility in Cases of Tyrosine Nitration-Associated Male Infertility in Mice
by Eleonora Scarlata, Maria C. Fernandez and Cristian O’Flaherty
Antioxidants 2020, 9(7), 613; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9070613 - 13 Jul 2020
Cited by 4 | Viewed by 2251
Abstract
Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for 50% of the cases. Currently, a physical examination, hormone profiling and the evaluation of two consecutive semen samples (to determine the sperm concentration, motility, [...] Read more.
Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for 50% of the cases. Currently, a physical examination, hormone profiling and the evaluation of two consecutive semen samples (to determine the sperm concentration, motility, morphology and, in very few cases, sperm DNA integrity) are the sole tools that physicians have to evaluate infertility in men. Antioxidant therapy is often used to improve sperm quality and function in infertile men. However, there are controversial results regarding the efficacy of these treatments. Prdx6−/− male mice are subfertile, displaying significant oxidative damage in the lipids, proteins and DNA of their spermatozoa. Here, we used Prdx6−/− male mice to test whether a novel combination of tocopherols that contained 60% γ-tocopherol and ascorbic acid could restore their fertility. These mice were fed with the supplemented (Vit. Mix) or control diets. To assess sperm quality, we determined the motility, levels of lipid peroxidation, DNA oxidation and tyrosine nitration in the spermatozoa. The number of pups sired by the Prdx6−/− mice fed with the Vit. Mix diet was higher than that sired by the males fed with the control diet, and the pups’ mortality was lower. The sperm quality was improved in the males fed with the supplemented diet. We concluded that treatment with a supplement composed of tocopherols and rich in γ-tocopherol and ascorbic acid is effective in restoring fertility in cases where oxidative stress and high levels of tyrosine nitration are associated with male infertility. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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Review

Jump to: Research

19 pages, 4461 KiB  
Review
Role of Antioxidants in Cooled Liquid Storage of Mammal Spermatozoa
by Miguel A. Silvestre, Jesús L. Yániz, Fernando J. Peña, Pilar Santolaria and María Castelló-Ruiz
Antioxidants 2021, 10(7), 1096; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071096 - 08 Jul 2021
Cited by 37 | Viewed by 5979
Abstract
Cooled preservation of semen is usually associated with artificial insemination and genetic improvement programs in livestock species. Several studies have reported an increase in reactive oxidative species and a decrease in antioxidant substances and sperm quality parameters during long-term semen storage at refrigerated [...] Read more.
Cooled preservation of semen is usually associated with artificial insemination and genetic improvement programs in livestock species. Several studies have reported an increase in reactive oxidative species and a decrease in antioxidant substances and sperm quality parameters during long-term semen storage at refrigerated temperatures. The supplementation of antioxidants in extenders before refrigeration could reduce this detrimental effect. Various antioxidants have been tested, both enzymatic, such as superoxide dismutase and catalase, and non-enzymatic, such as reduced glutathione, vitamins E and C and melatonin. However, the problem of oxidative stress in semen storage has not been fully resolved. The effects of antioxidants for semen-cooled storage have not been reviewed in depth. Therefore, the objective of the present study was to review the efficiency of the supplementation of antioxidants in the extender during cooled storage of semen in livestock species. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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24 pages, 1892 KiB  
Review
Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development
by Roberto Gualtieri, Guruprasad Kalthur, Vincenza Barbato, Salvatore Longobardi, Francesca Di Rella, Satish Kumar Adiga and Riccardo Talevi
Antioxidants 2021, 10(7), 1025; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071025 - 25 Jun 2021
Cited by 43 | Viewed by 6018
Abstract
Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell’s antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa [...] Read more.
Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell’s antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa regulates essential functional characteristics such as motility, capacitation, acrosome reaction, hyperactivation, and sperm-oocyte fusion. OS can have detrimental effects on sperm function through lipid peroxidation, protein damage, and DNA strand breakage, which can eventually affect the fertility of an individual. Substantial evidence in the literature indicates that spermatozoa experiencing OS during in vitro manipulation procedures in human- and animal-assisted reproduction are increasingly associated with iatrogenic ROS production and eventual impairment of sperm function. Although a direct association between sperm OS and human assisted reproductive techniques (ART) outcomes after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) is still a matter of debate, studies in animal models provide enough evidence on the adverse effects of sperm OS in vitro and defective fertilization and embryo development. This review summarized the literature on sperm OS in vitro, its effects on functional ability and embryo development, and the approaches that have been proposed to reduce iatrogenic sperm damage and altered embryonic development. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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25 pages, 2296 KiB  
Review
Plant Extracts as Alternative Additives for Sperm Preservation
by José Luis Ros-Santaella and Eliana Pintus
Antioxidants 2021, 10(5), 772; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10050772 - 13 May 2021
Cited by 28 | Viewed by 6119
Abstract
Sperm preservation is a crucial factor for the success of assisted reproductive technology (ART) in humans, livestock, and wildlife. Irrespective of the extender and the storage conditions used, semen handling and preservation negatively affect sperm quality. Moreover, oxidative stress, which often arises during [...] Read more.
Sperm preservation is a crucial factor for the success of assisted reproductive technology (ART) in humans, livestock, and wildlife. Irrespective of the extender and the storage conditions used, semen handling and preservation negatively affect sperm quality. Moreover, oxidative stress, which often arises during semen storage, significantly reduces sperm function and compromises the sperm fertilizing ability by inducing oxidative damage to proteins, lipids, and nucleic acids. Plant extracts have recently emerged as a cheap and natural source of additives to preserve and enhance sperm function during semen storage. The present work provides an update on the use of these natural compounds as alternative additives for sperm preservation in 13 animal species, including humans. A detailed description of the effects of 45 plant species, belonging to 28 families, on sperm function during semen storage is presented. The plant material and extraction method employed, dosage, possible toxic effects, and antimicrobial properties are provided. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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31 pages, 1536 KiB  
Review
Antioxidant-Based Therapies in Male Infertility: Do We Have Sufficient Evidence Supporting Their Effectiveness?
by Angela Maria Amorini, Ilaria Listorti, Gabriele Bilotta, Romina Pallisco, Miriam Wissam Saab, Renata Mangione, Benedetta Manca, Giacomo Lazzarino, Barbara Tavazzi, Giuseppe Lazzarino and Pasquale Bilotta
Antioxidants 2021, 10(2), 220; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10020220 - 02 Feb 2021
Cited by 12 | Viewed by 6153
Abstract
Under physiological conditions, reactive oxygen species (ROS) play pivotal roles in various processes of human spermatozoa. Indeed, semen requires the intervention of ROS to accomplish different stages of its maturation. However, ROS overproduction is a well-documented phenomenon occurring in the semen of infertile [...] Read more.
Under physiological conditions, reactive oxygen species (ROS) play pivotal roles in various processes of human spermatozoa. Indeed, semen requires the intervention of ROS to accomplish different stages of its maturation. However, ROS overproduction is a well-documented phenomenon occurring in the semen of infertile males, potentially causing permanent oxidative damages to a vast number of biological molecules (proteins, nucleic acids, polyunsaturated fatty acids of biological membrane lipids), negatively affecting the functionality and vitality of spermatozoa. ROS overproduction may concomitantly occur to the excess generation of reactive nitrogen species (RNS), leading to oxidative/nitrosative stress and frequently encountered in various human pathologies. Under different conditions of male infertility, very frequently accompanied by morpho-functional anomalies in the sperm analysis, several studies have provided evidence for clear biochemical signs of damages to biomolecules caused by oxidative/nitrosative stress. In the last decades, various studies aimed to verify whether antioxidant-based therapies may be beneficial to treat male infertility have been carried out. This review analyzed the results of the studies published during the last ten years on the administration of low-molecular-weight antioxidants to treat male infertility in order to establish whether there is a sufficient number of data to justify antioxidant administration to infertile males. An analysis of the literature showed that only 30 clinical studies tested the effects of the administration of low-molecular-weight antioxidants (administered as a single antioxidant or as a combination of different antioxidants with the addition of vitamins and/or micronutrients) to infertile males. Of these studies, only 33.3% included pregnancy and/or live birth rates as an outcome measure to determine the effects of the therapy. Of these studies, only 4 were case–control studies, and only 2 of them found improvement of the pregnancy rate in the group of antioxidant-treated patients. Additionally, of the 30 studies considered in this review, only 43.3% were case–control studies, 66.7% enrolled a number of patients higher than 40, and 40% carried out the administration of a single antioxidant. Therefore, it appears that further studies are needed to clearly define the usefulness of antioxidant-based therapies to treat male infertility. Full article
(This article belongs to the Special Issue Oxidative Stress, Antioxidants and Male Reproduction)
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