Antioxidants and Male Infertility

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 (31 July 2021) | Viewed by 47577

Special Issue Editors


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Guest Editor
Faculty of Health Sciences, University of Beira Interior, Portugal
Interests: antioxidants; diabetes; functional foods; male infertility; medicinal plants; polyphenols

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Guest Editor
QOPNA & LAQV, Department of Chemistry, University of Aveiro, Aveiro, Portugal
Interests: male fertility; antioxidants; sperm quality; oxidative stress; cell metabolism and bioenergetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are leading the following Special Issue entitled “Antioxidants and Male Infertility” in the journal Antioxidants.

Antioxidants are commonly known as substances that can inhibit, reduce, or delay damage to cells caused by free radicals. In turn, free radicals can be defined as unstable molecules capable of independent existence that contain an unpaired electron in an atomic orbital. They attack important macromolecules, such as lipids, nucleic acids, and proteins, leading to cell damage and homeostatic disruption.

Infertility affects about 15% of couples trying to conceive, and factors associated with the male partner contribute to half of these cases. The deleterious effects of oxidative stress (OS) have been strongly associated with decreased sperm quality and male infertility. In fact, although reactive oxygen species (ROS) are crucial for some reproductive processes, namely in capacitation and acrosome reaction, augmented ROS levels, along with decreased endogenous antioxidant defenses, result in an OS status that ultimately leads to sperm membrane lipid peroxidation, reduced motility, and sperm DNA damage.

Exogenous natural antioxidants have received great attention because of their beneficial role in male subfertility and infertility. Contributions to this Special Issue may cover all research aspects related to antioxidants, especially those from natural origin, as well as male subfertility and infertility.

We look forward to receiving your contributions.

Prof. Dr. Pedro F. Oliveira
Prof. Dr. Branca M. Silva
Guest Editors

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Keywords

  • Functional foods
  • Male fertility
  • Medicinal plants
  • Natural antioxidants
  • Oxidative stress
  • Phenolic compounds
  • Phytochemicals
  • Sperm quality

Published Papers (13 papers)

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Editorial

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3 pages, 201 KiB  
Editorial
Antioxidants and Male Infertility
by Ricardo Silva, David F. Carrageta, Marco G. Alves, Branca M. Silva and Pedro F. Oliveira
Antioxidants 2022, 11(6), 1152; https://doi.org/10.3390/antiox11061152 - 12 Jun 2022
Cited by 4 | Viewed by 1956
Abstract
Oxidative stress has been associated with decreased sperm quality and male infertility [...] Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)

Research

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12 pages, 2650 KiB  
Article
Oxidative Stress Measurement in Frozen/Thawed Human Sperm: The Protective Role of an In Vitro Treatment with Myo-Inositol
by Rosetta Ponchia, Annunziata Bruno, Asia Renzi, Claudia Landi, Enxhi Shaba, Francesca Paola Luongo, Alesandro Haxhiu, Paolo Giovanni Artini, Alice Luddi, Laura Governini and Paola Piomboni
Antioxidants 2022, 11(1), 10; https://doi.org/10.3390/antiox11010010 - 22 Dec 2021
Cited by 19 | Viewed by 3449
Abstract
Despite its widespread use, sperm cryopreservation induces serious detrimental alterations in sperm function; indeed, it is commonly associated with decreased sperm viability and motility, and DNA fragmentation. Mechanisms of human sperm cryodamage are thought to be multifactorial, but oxidative stress seems to have [...] Read more.
Despite its widespread use, sperm cryopreservation induces serious detrimental alterations in sperm function; indeed, it is commonly associated with decreased sperm viability and motility, and DNA fragmentation. Mechanisms of human sperm cryodamage are thought to be multifactorial, but oxidative stress seems to have a prominent role. A huge amount of data supported the cryoprotective effect of different antioxidants able to minimize the detrimental effects of reactive oxygen species (ROS) and improve the quality of spermatozoa. Among others, myo-inositol is one of the most powerful and has been reported to be effective in improving sperm quality and motility when used both in vivo and in vitro. This study aimed to determine the in vitro impact of myo-inositol in ameliorating sperm oxidative status during sperm cryopreservation. In particular, we demonstrated a significant improvement of sperm parameters (vitality and motility) when myo-inositol was added after sperm thawing (p < 0.05). Moreover, we showed that myo-inositol induces a significant increase in oxygen consumption, the main index of oxidative phosphorylation efficiency and ATP production. Finally, by means of 2D-electrophoresis, we demonstrated a significant decrease in the level of carbonyl groups, the main structural changes occurring in conditions of oxidative stress (p < 0.05). In conclusion, the sperm cryopreservation procedure we developed, assuring the reduction of ROS-induced sperm modifications, may improve the in vitro procedure currently used in ART laboratory for sperm cryostorage. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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16 pages, 1445 KiB  
Article
Improving Sperm Oxidative Stress and Embryo Quality in Advanced Paternal Age Using Idebenone In Vitro—A Proof-of-Concept Study
by Victoria Nikitaras, Deirdre Zander-Fox and Nicole O. McPherson
Antioxidants 2021, 10(7), 1079; https://doi.org/10.3390/antiox10071079 - 05 Jul 2021
Cited by 15 | Viewed by 2574
Abstract
Advanced paternal age is associated with increased sperm reactive oxygen species (ROS) and decreased fertilization and pregnancy rates. Sperm washing during infertility treatment provides an opportunity to reduce high sperm ROS concentrations associated with advanced paternal age through the addition of idebenone. Sperm [...] Read more.
Advanced paternal age is associated with increased sperm reactive oxygen species (ROS) and decreased fertilization and pregnancy rates. Sperm washing during infertility treatment provides an opportunity to reduce high sperm ROS concentrations associated with advanced paternal age through the addition of idebenone. Sperm from men aged >40 years and older CBAF1 mice (12–18 months), were treated with 5 µM and 50 µM of idebenone and intracellular and superoxide ROS concentrations assessed. Following in vitro fertilization (IVF), embryo development, blastocyst differentiation, DNA damage and cryosurvival, pregnancy and implantation rates and fetal and placental weights were assessed. Five µM of idebenone given to aged human and mouse sperm reduced superoxide concentrations ~20% (p < 0.05), while both 5 and 50 µM reduced sperm intracellular ROS concentrations in mice ~30% (p < 0.05). Following IVF, 5 µM of idebenone to aged sperm increased fertilization rates (65% vs. 60%, p < 0.05), blastocyst total, trophectoderm and inner cell mass cell numbers (73 vs. 66, 53 vs. 47 and 27 vs. 24, respectively, p < 0.01). Treatment with idebenone also increased blastocyst cryosurvival rates (96% vs. 78%, p < 0.01) and implantation rates following embryo transfer (35% vs. 18%, p < 0.01). Placental weights were smaller (107 mg vs. 138 mg, p < 0.05), resulting in a larger fetal to placental weight ratio (8.3 vs. 6.3, p = 0.07) after sperm idebenone treatment. Increased sperm ROS concentrations associated with advanced paternal age are reduced with the addition of idebenone in vitro, and are associated with improved fertilization rates, embryo quality and implantation rates after IVF. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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22 pages, 5704 KiB  
Article
Accumulation of Seminolipid in Sertoli Cells Is Associated with Increased Levels of Reactive Oxygen Species and Male Subfertility: Studies in Aging Arsa Null Male Mice
by Kessiri Kongmanas, Arpornrad Saewu, Wongsakorn Kiattiburut, Mark A Baker, Kym F Faull, Dylan Burger and Nongnuj Tanphaichitr
Antioxidants 2021, 10(6), 912; https://doi.org/10.3390/antiox10060912 - 04 Jun 2021
Cited by 6 | Viewed by 2385
Abstract
Seminolipid (also known as sulfogalactosylglycerolipid-SGG), present selectively in male germ cells, plays important roles in spermatogenesis and sperm–egg interaction. The proper degradation of SGG in apoptotic germ cells is also as important. Sertoli cells first phagocytose apoptotic germ cells, then Sertoli lysosomal arylsulfatase [...] Read more.
Seminolipid (also known as sulfogalactosylglycerolipid-SGG), present selectively in male germ cells, plays important roles in spermatogenesis and sperm–egg interaction. The proper degradation of SGG in apoptotic germ cells is also as important. Sertoli cells first phagocytose apoptotic germ cells, then Sertoli lysosomal arylsulfatase A (ARSA) desulfates SGG, the first step of SGG degradation. We have reported that aging male Arsa−/− mice become subfertile with SGG accumulation in Sertoli cell lysosomes, typical of a lysosomal storage disorder (LSD). Since reactive oxygen species (ROS) levels are increased in other glycolipid-accumulated LSDs, we quantified ROS in Arsa−/− Sertoli cells. Our analyses indicated increases in superoxide and H2O2 in Arsa−/− Sertoli cells with elevated apoptosis rates, relative to WT counterparts. Excess H2O2 from Arsa−/− Sertoli cells could travel into testicular germ cells (TGCs) to induce ROS production. Our results indeed indicated higher superoxide levels in Arsa−/− TGCs, compared with WT TGCs. Increased ROS levels in Arsa−/− Sertoli cells and TGCs likely caused the decrease in spermatogenesis and increased the abnormal sperm population in aging Arsa−/− mice, including the 50% decrease in sperm SGG with egg binding ability. In summary, our study indicated that increased ROS production was the mechanism through which subfertility manifested following SGG accumulation in Sertoli cells. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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15 pages, 12924 KiB  
Article
Hidrox® Counteracts Cyclophosphamide-Induced Male Infertility through NRF2 Pathways in a Mouse Model
by Roberta Fusco, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Roberto Crea, Marika Cordaro, Salvatore Cuzzocrea, Rosanna Di Paola and Vittorio Calabrese
Antioxidants 2021, 10(5), 778; https://doi.org/10.3390/antiox10050778 - 14 May 2021
Cited by 45 | Viewed by 3357
Abstract
Background: Every year, men use cyclophosphamide to treat various cancers and autoimmune diseases. On the one hand, this chemotherapy often has the beneficial effect of regressing the tumor, but on the other hand, it leads to infertility due to excessive oxidative stress and [...] Read more.
Background: Every year, men use cyclophosphamide to treat various cancers and autoimmune diseases. On the one hand, this chemotherapy often has the beneficial effect of regressing the tumor, but on the other hand, it leads to infertility due to excessive oxidative stress and apoptosis in the testes caused by its metabolite, acrolein. Methods: The objective of this study was to evaluate the beneficial power of a new compound called Hidrox®, containing 40–50% hydroxytyrosol, in counteracting the damage related to fertility induced by cyclophosphamide. The study was conducted using a single intraperitoneal injection of cyclophosphamide at a dose of 200 mg/kg b.w, in distilled water at 10 mL/kg b.w. The treatment was administered via the oral administration of Hidrox® at a dose of 50 mg/kg. Results: Our study confirms that the use of cyclophosphamide causes a series of sperm and histological alterations strongly connected with oxidative stress, lipid peroxidation, and apoptosis. Conclusion: Our results demonstrate for the first time that Hidrox® protects testes from CYP-induced alterations by the modulation of physiological antioxidant defenses. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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14 pages, 776 KiB  
Article
Oxidative Stress Is Associated with Telomere Interaction Impairment and Chromatin Condensation Defects in Spermatozoa of Infertile Males
by Benoit Berby, Cynthia Bichara, Aurélie Rives-Feraille, Fanny Jumeau, Pierre Di Pizio, Véronique Sétif, Louis Sibert, Ludovic Dumont, Chistine Rondanino and Nathalie Rives
Antioxidants 2021, 10(4), 593; https://doi.org/10.3390/antiox10040593 - 12 Apr 2021
Cited by 20 | Viewed by 2857
Abstract
Telomere length can be influenced by reactive oxygen species (ROS) generated by lifestyle factors or environmental exposure. We sought to determine whether oxidative stress has an impact on sperm nuclear alterations, especially on chromatin organization and telomere interactions in the spermatozoa of infertile [...] Read more.
Telomere length can be influenced by reactive oxygen species (ROS) generated by lifestyle factors or environmental exposure. We sought to determine whether oxidative stress has an impact on sperm nuclear alterations, especially on chromatin organization and telomere interactions in the spermatozoa of infertile males. We performed an observational and prospective study including fifty-two males, allocated in the “case group” (30 infertile males presenting conventional semen parameter alterations) and the “control group” (22 males with normal conventional semen parameters). ROS detection was determined on spermatozoa using CellROX© probes. Sperm nuclear damage was assessed using quantitative fluorescence in situ hybridization (Q-FISH) for relative telomere length and telomere number, aniline blue staining for chromatin condensation, terminal deoxynucleotidyl transferase dUTP nick-end labeling for DNA fragmentation, and FISH for aneuploidy and 8-hydroxy-2′-deoxyguanosine immunostaining for oxidative DNA damages. Infertile males had significantly increased levels of cytoplasmic ROS and chromatin condensation defects as well as a higher mean number of telomere signals per spermatozoon in comparison with controls. In addition, the mean number of sperm telomere signals were positively correlated with the percentage of spermatozoa with chromatin condensation defect. In infertile males with conventional semen parameter alterations, oxidative stress is associated with telomere interaction impairment and chromatin condensation defects. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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13 pages, 1079 KiB  
Article
Mitigating the Effects of Oxidative Sperm DNA Damage
by Taylor Pini, Rachel Makloski, Karen Maruniak, William B. Schoolcraft and Mandy G. Katz-Jaffe
Antioxidants 2020, 9(7), 589; https://doi.org/10.3390/antiox9070589 - 06 Jul 2020
Cited by 7 | Viewed by 2898
Abstract
Sperm DNA damage is correlated with reduced embryo development and increased miscarriage risk, reducing successful conception. Given its links with oxidative stress, antioxidants have been investigated as a potential treatment, yet results are conflicting. Importantly, individual antioxidants are not identical in composition, and [...] Read more.
Sperm DNA damage is correlated with reduced embryo development and increased miscarriage risk, reducing successful conception. Given its links with oxidative stress, antioxidants have been investigated as a potential treatment, yet results are conflicting. Importantly, individual antioxidants are not identical in composition, and some compounds may be more effective than others. We investigated the use of the polyphenol-rich, high-antioxidant-capacity fruit acai as a treatment for elevated sperm DNA fragmentation (>16%), measured by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Following ≥ 74 days of treatment, we observed a significant decrease in sperm DNA fragmentation (−17.0% ± 2.5%) to 11.9 ± 1.7% (0–37%), with a 68.6% success rate (defined as post-treatment TUNEL < 16%). Post-treatment decreases in DNA fragmentation and success rates were not significantly impacted by low motility and/or concentration, or exceptionally high (> 25%) TUNEL. Treatment significantly reduced concentration in men with normal semen parameters, but 88% remained normal. Overall, successful treatment was not associated with age, semen parameters or TUNEL result at baseline. However, body mass index was significantly higher in nonresponders at baseline. This study provides evidence of a low-cost, effective treatment for elevated sperm DNA damage using acai. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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Review

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21 pages, 12800 KiB  
Review
Redox Balance in Male Infertility: Excellence through Moderation—“Μέτρον ἄριστον”
by Evangelos N. Symeonidis, Evangelini Evgeni, Vasileios Palapelas, Dimitra Koumasi, Nikolaos Pyrgidis, Ioannis Sokolakis, Georgios Hatzichristodoulou, Chara Tsiampali, Ioannis Mykoniatis, Athanasios Zachariou, Nikolaos Sofikitis, Ares Kaltsas and Fotios Dimitriadis
Antioxidants 2021, 10(10), 1534; https://doi.org/10.3390/antiox10101534 - 27 Sep 2021
Cited by 20 | Viewed by 2789
Abstract
Male infertility, a relatively common and multifactorial medical condition, affects approximately 15% of couples globally. Based on WHO estimates, a staggering 190 million people struggle with this health condition, and male factor is the sole or contributing factor in roughly 20–50% of these [...] Read more.
Male infertility, a relatively common and multifactorial medical condition, affects approximately 15% of couples globally. Based on WHO estimates, a staggering 190 million people struggle with this health condition, and male factor is the sole or contributing factor in roughly 20–50% of these cases. Nowadays, urologists are confronted with a wide spectrum of conditions ranging from the typical infertile male to more complex cases of either unexplained or idiopathic male infertility, requiring a specific patient-tailored diagnostic approach and management. Strikingly enough, no identifiable cause in routine workup can be found in 30% to 50% of infertile males. The medical term male oxidative stress infertility (MOSI) was recently coined to describe infertile men with abnormal sperm parameters and oxidative stress (OS), including those previously classified as having idiopathic infertility. OS is a critical component of male infertility, entailing an imbalance between reactive oxygen species (ROS) and antioxidants. ROS abundance has been implicated in sperm abnormalities, while the exact impact on fertilization and pregnancy has long been a subject of considerable debate. In an attempt to counteract the deleterious effects of OS, urologists resorted to antioxidant supplementation. Mounting evidence indicates that indiscriminate consumption of antioxidants has led in some cases to sperm cell damage through a reductive-stress-induced state. The “antioxidant paradox”, one of the biggest andrological challenges, remains a lurking danger that needs to be carefully avoided and thoroughly investigated. For that reason, oxidation-reduction potential (ORP) emerged as a viable ancillary tool to basic semen analysis, measuring the overall balance between oxidants and antioxidants (reductants). A novel biomarker, the Male infertility Oxidative System (MiOXSYS®), is a paradigm shift towards that goal, offering a quantification of OS via a quick, reliable, and reproducible measurement of the ORP. Moderation or “Μέτρον” according to the ancient Greeks is the key to successfully safeguarding redox balance, with MiOXSYS® earnestly claiming its position as a guarantor of homeostasis in the intracellular redox milieu. In the present paper, we aim to offer a narrative summary of evidence relevant to redox regulation in male reproduction, analyze the impact of OS and reductive stress on sperm function, and shed light on the “antioxidant paradox” phenomenon. Finally, we examine the most up-to-date scientific literature regarding ORP and its measurement by the recently developed MiOXSYS® assay. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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24 pages, 2618 KiB  
Review
Impact of Heavy Metals on Human Male Fertility—An Overview
by Andrea López-Botella, Irene Velasco, Maribel Acién, Paula Sáez-Espinosa, José-Luis Todolí-Torró, Raquel Sánchez-Romero and María José Gómez-Torres
Antioxidants 2021, 10(9), 1473; https://doi.org/10.3390/antiox10091473 - 15 Sep 2021
Cited by 39 | Viewed by 5764
Abstract
Heavy metals are endocrine disruptors which interfere with processes mediated by endogenous hormones of the organism, negatively affecting endocrine functions. Some studies have correlated heavy metal exposure with male infertility. However, the number of studies conducted on humans are limited. Therefore, the aim [...] Read more.
Heavy metals are endocrine disruptors which interfere with processes mediated by endogenous hormones of the organism, negatively affecting endocrine functions. Some studies have correlated heavy metal exposure with male infertility. However, the number of studies conducted on humans are limited. Therefore, the aim of this study is to summarize the current knowledge on how heavy metals influence human male fertility. Hence, three distinct databases were consulted—PubMed, Scopus and Web of Science—using single keywords and combinations of them. The total number of identified articles was 636. Nevertheless, by using the inclusion and exclusion criteria, 144 articles were finally included in this work. Results display that the development of adequate instruments for heavy metal assessment may play an important function in human male fertility diagnosis and treatment. Furthermore, clinical trials could be useful to confirm the role of heavy metals in human male fertility diagnosis. Overall, further research is required to fully understand the molecular and cellular basis of the influence of environmental and occupational exposure to heavy metals on human male infertility and reproductive outcomes. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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28 pages, 2476 KiB  
Review
Antioxidants Present in Reproductive Tract Fluids and Their Relevance for Fertility
by João C. Ribeiro, Patrícia C. Braga, Ana D. Martins, Branca M. Silva, Marco G. Alves and Pedro F. Oliveira
Antioxidants 2021, 10(9), 1441; https://doi.org/10.3390/antiox10091441 - 09 Sep 2021
Cited by 16 | Viewed by 3873
Abstract
Nowadays, infertility is classified as a disease of the reproductive system. Although it does not compromise the life of the individual, it can have detrimental effects on the physiological and psychological health of the couple. Male fertility evaluation is mainly focused on the [...] Read more.
Nowadays, infertility is classified as a disease of the reproductive system. Although it does not compromise the life of the individual, it can have detrimental effects on the physiological and psychological health of the couple. Male fertility evaluation is mainly focused on the analysis of sperm parameters. However, the ejaculated fluid is also composed of seminal plasma, and the study of this fluid can provide crucial information to help in the assessment of male fertility status. Total antioxidant capacity of the seminal plasma has been positively correlated with the fertility of men. Moreover, evidence highlights to a similar importance as that of female reproductive tract fluid antioxidant capabilities and female fertility. Herein, we describe the functions of seminal plasma and female reproductive tract fluids, as well as their main antioxidant components and their relationships with fertility outcomes. Additionally, this review contains the most up to date information regarding the mechanisms of the interaction between the male and the female reproductive fluids and the importance of proper antioxidant capacity for fertilization. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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21 pages, 1139 KiB  
Review
Fighting Bisphenol A-Induced Male Infertility: The Power of Antioxidants
by Joana Santiago, Joana V. Silva, Manuel A. S. Santos and Margarida Fardilha
Antioxidants 2021, 10(2), 289; https://doi.org/10.3390/antiox10020289 - 15 Feb 2021
Cited by 33 | Viewed by 6259
Abstract
Bisphenol A (BPA), a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic–pituitary–gonadal axis and inducing oxidative [...] Read more.
Bisphenol A (BPA), a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic–pituitary–gonadal axis and inducing oxidative stress in testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestradiol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, and sperm DNA damage. Recent studies explored potential approaches to treat or prevent BPA-induced testicular toxicity and male infertility. Since the effect of BPA on testicular cells and spermatozoa is associated with an increased production of reactive oxygen species, most of the pharmacological approaches are based on the use of natural or synthetic antioxidants. In this review, we briefly describe the effects of BPA on male reproductive health and discuss the use of antioxidants to prevent or revert the BPA-induced toxicity and infertility in men. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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15 pages, 1759 KiB  
Review
Oxidation of Sperm DNA and Male Infertility
by Leila Rashki Ghaleno, AliReza Alizadeh, Joël R. Drevet, Abdolhossein Shahverdi and Mojtaba Rezazadeh Valojerdi
Antioxidants 2021, 10(1), 97; https://doi.org/10.3390/antiox10010097 - 12 Jan 2021
Cited by 47 | Viewed by 4787
Abstract
One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm [...] Read more.
One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm cell specific cytologic and metabolic features (no cytoplasm left and cells unable to mount stress responses) make it the cell type in metazoans most susceptible to oxidative damage. In particular, oxidative damage to the spermatozoa genome is an important issue and a cause of male infertility, usually associated with single- or double-strand paternal DNA breaks. Various methods of detecting sperm DNA fragmentation have become important diagnostic tools in the prognosis of male infertility and such assays are available in research laboratories and andrology clinics. However, to date, there is not a clear consensus in the community as to their respective prognostic value. Nevertheless, it is important to understand that the effects of oxidative stress on the sperm genome go well beyond DNA fragmentation alone. Oxidation of paternal DNA bases, particularly guanine and adenosine residues, the most sensitive residues to oxidative alteration, is the starting point for DNA damage in spermatozoa but is also a danger for the integrity of the embryo genetic material independently of sperm DNA fragmentation. Due to the lack of a spermatozoa DNA repair system and, if the egg is unable to correct the sperm oxidized bases, the risk of de novo mutation transmission to the embryo exists. These will be carried on to every cell of the future individual and its progeny. Thus, in addition to affecting the viability of the pregnancy itself, oxidation of the DNA bases in sperm could be associated with the development of conditions in young and future adults. Despite these important issues, sperm DNA base oxidation has not attracted much interest among clinicians due to the lack of simple, reliable, rapid and consensual methods of assessing this type of damage to the paternal genome. In addition to these technical issues, another reason explaining why the measurement of sperm DNA oxidation is not included in male fertility is likely to be due to the lack of strong evidence for its role in pregnancy outcome. It is, however, becoming clear that the assessment of DNA base oxidation could improve the efficiency of assisted reproductive technologies and provide important information on embryonic developmental failures and pathologies encountered in the offspring. The objective of this work is to review relevant research that has been carried out in the field of sperm DNA base oxidation and its associated genetic and epigenetic consequences. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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Other

15 pages, 2649 KiB  
Systematic Review
The Effect of Antioxidant Supplementation on Operated or Non-Operated Varicocele-Associated Infertility: A Systematic Review and Meta-Analysis
by Nikolaos Pyrgidis, Ioannis Sokolakis, Vasileios Palapelas, Maksim Tishukov, Ioannis Mykoniatis, Evangelos N. Symeonidis, Athanasios Zachariou, Aris Kaltsas, Nikolaos Sofikitis, Georgios Hatzichristodoulou, Chara Tsiampali and Fotios Dimitriadis
Antioxidants 2021, 10(7), 1067; https://doi.org/10.3390/antiox10071067 - 01 Jul 2021
Cited by 10 | Viewed by 2984
Abstract
In patients with varicocele-associated infertility, the effect of antioxidant supplementation on fertility is unknown. We performed a systematic review and meta-analysis to explore their role in patients with operated or non-operated varicocele. We searched major databases and sources of grey literature until May [...] Read more.
In patients with varicocele-associated infertility, the effect of antioxidant supplementation on fertility is unknown. We performed a systematic review and meta-analysis to explore their role in patients with operated or non-operated varicocele. We searched major databases and sources of grey literature until May 2021 (PROSPERO: CRD42021248195). We included 14 studies (980 individuals) in the systematic review. Of the 14 studies, 2 explored the effect of antioxidant supplementation in patients with non-operated varicocele, 1 compared antioxidants versus surgical repair of varicocele, while 11 explored antioxidants after surgical repair of varicocele and were also included in the meta-analysis. Regarding pregnancy rates, no significant differences were demonstrated after treatment with antioxidants versus no treatment at three (OR: 2.28, 95% CI: 0.7–7.48) and six months (OR: 1.88, 95% CI: 0.62–5.72). Accordingly, contradictory findings were reported in sperm concentration, morphology, and motility, as well as DNA fragmentation. Our findings indicate that antioxidant supplementation does not improve pregnancy rates and semen parameters in patients with varicocele-associated infertility, in the absence of previous screening for oxidative stress. Based on the previous notion, most included studies also raised methodological concerns. Therefore, definitive conclusions about the efficacy of antioxidant supplementation in this setting cannot be drawn and further research on the field is mandatory. Full article
(This article belongs to the Special Issue Antioxidants and Male Infertility)
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