Redox Signal in the Reproductive System

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 (15 November 2021) | Viewed by 25044

Special Issue Editors


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Guest Editor
Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano, 49, 80131 Napoli, Italy
Interests: nitric oxide; hydrogen sulfide; vascular reactivity; endothelial dysfunction; erectile dysfunction; urogenital tract; lung inflammation; platelet activity

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Guest Editor
Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy
Interests: gaseous transmitters; endothelial dysfunction; smooth muscle cells; vascular-based inflammatory disease; erectile dysfunction; bladder disorder

Special Issue Information

Dear Colleagues,

Redox signaling is a common form of cellular communication within a living organism and is an essential function of normal physiology. In this regard, the urogenital system, like other systems, is constantly exposed to molecules that come from these reactions and act as either cellular messengers or cellular activators. Our body is under constant oxidative attack from reactive oxygen species (ROS) that come from physiological reactions causing oxidative stress. In this context, the mitochondria are one of the central actors or the targets of the damage. Our body is equipped with a complex system of antioxidant mechanisms/molecules that generally holds this attack in balance. However, it can occasionally be perturbed. This leads to oxidative stress, which is now recognized to play a central role in the pathophysiology of many different disorders. Thus, in certain conditions depending upon genetic or epigenetic alterations associated with lifestyle and environmental factors (i.e., anthropogenic compounds), this unbalance could cause cell or organ damage affecting specific pathologies of the urogenital/reproductive system. For example, these alterations can affect the biological competence of oocyte and sperm, erectile function, sperm capacitation, and pregnancy, causing pathologies such as preeclampsia, placental disease, and alteration during fetus development. The oxidative stress may also act indirectly by affecting the hypothalamus–pituitary–gonadal axis and/or disrupting its crosstalk with other hormonal axes. Redox alteration can also increase the risk of developing urolithiasis, renal fibrosis, and bladder disorders.

Therefore, in this Special Issue, original research papers or review articles that consider different aspects associated with redox status alteration(s) in the reproductive or urogenital system, either in preclinical or clinical stages, and aim to identify therapeutic targets (mechanisms/pathways) are more than welcome.

Prof. Dr. Raffaella Sorrentino
Prof. Dr. Roberta d'Emmanuele di Villa Bianca
Guest Editors

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Keywords

  • ROS
  • Oxidative stress
  • Gaseous transmitters
  • Antioxidants
  • Reproductive system
  • Urogenital tract
  • Oocyte
  • Sperm
  • Fertility
  • Endometriosis
  • Endothelial dysfunction
  • Erectile dysfunction

Published Papers (8 papers)

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Research

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15 pages, 3205 KiB  
Article
Intracellular Pathways of Holothuroid Oocyte Maturation Induced by the Thioredoxin Trx-REES
by Jérôme Delroisse, Aline Léonet, Henri Alexandre and Igor Eeckhaut
Antioxidants 2021, 10(8), 1201; https://doi.org/10.3390/antiox10081201 - 27 Jul 2021
Cited by 2 | Viewed by 2001
Abstract
In holothuroids, oocyte maturation is stopped in ovaries at the prophase I stage of meiosis. In natural conditions, the blockage is removed during the spawning by an unknown mechanism. When oocytes are isolated by dissection, the meiotic release can be successfully induced by [...] Read more.
In holothuroids, oocyte maturation is stopped in ovaries at the prophase I stage of meiosis. In natural conditions, the blockage is removed during the spawning by an unknown mechanism. When oocytes are isolated by dissection, the meiotic release can be successfully induced by a natural inducer, the REES (i.e., Rough Extract of Echinoid Spawn) that is used in aquaculture to obtain viable larvae in mass. A thioredoxin has recently been identified in the REES as the molecule responsible for holothuroid oocyte maturation. As a redox-active protein, thioredoxin is thought to reduce target proteins within the oocyte membrane and initiate an intracellular reaction cascade that leads to the unblocking of the oocyte meiosis. Our results allow us to understand additional steps in the intracellular reaction cascade induced by the action of thioredoxin on oocytes. Pharmacological agents known to have activating or inhibiting actions on oocyte maturation have been used (Forskolin, Isobutylmethylxanthine, Hypoxanthine, 6-dimethyaminopurine, Lavendustin, Genistein, Roscovitine, Cycloheximide). The effects of these agents were analysed on oocytes of the holothuroid Holothuria tubulosa incubated with or without REES and were compared to those obtained with another reducing agent, the dithiothreitol. Our results demonstrated that, at the opposite of dithiothreitol-induced oocyte maturation, thioredoxin-induced oocyte maturation is cAMP independent, but dependent of the presence of calcium in the seawater. Both pathways of induction require the activation of protein serine/threonine kinases. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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18 pages, 1429 KiB  
Article
Is There a Balance in Oxidative-Antioxidant Status in Blood Serum of Patients with Advanced Endometriosis?
by Izabela Kokot, Agnieszka Piwowar, Marcin Jędryka and Ewa Maria Kratz
Antioxidants 2021, 10(7), 1097; https://doi.org/10.3390/antiox10071097 - 08 Jul 2021
Cited by 12 | Viewed by 2493
Abstract
Can redox homeostasis indicators be potential non-invasive markers, crucial in the diagnosis and treatment of endometriosis? We checked if the differences in levels of serum oxidative-antioxidant balance parameters (TAS, FRAP, albumin, total bilirubin, uric acid, iron, SIRT3, SIRT5, SIRT6, telomerase, AOPP) are significant [...] Read more.
Can redox homeostasis indicators be potential non-invasive markers, crucial in the diagnosis and treatment of endometriosis? We checked if the differences in levels of serum oxidative-antioxidant balance parameters (TAS, FRAP, albumin, total bilirubin, uric acid, iron, SIRT3, SIRT5, SIRT6, telomerase, AOPP) are significant between patients with advanced endometriosis (E), healthy women (control group, C) and non-endometriosis women, but with other gynecological disorders (NE). The FRAP concentrations were significantly higher in E and NE group than in the control group (p = 0.015 and p = 0.017, respectively). The telomerase concentrations were significantly higher in the endometriosis group than in the control group (p = 0.004). Significantly higher concentrations of AOPP were observed in E (p < 0.001) and NE groups (p = 0.028) in comparison to the control subjects. Between stages III and IV of endometriosis, a significant difference existed only in concentration of iron (p = 0.013). There were no significant differences between the studied groups in the values of the remaining parameters. Based on the results of ROC curve analysis, we can conclude that the levels of serum FRAP, telomerase and AOPP may be taken into account as promising diagnostics markers that reflect the degree of oxidative stress accompanying advanced endometriosis. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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14 pages, 3370 KiB  
Article
Modulation of Intracellular ROS and Senescence-Associated Phenotypes of Xenopus Oocytes and Eggs by Selective Antioxidants
by Alexander A. Tokmakov and Ken-Ichi Sato
Antioxidants 2021, 10(7), 1068; https://doi.org/10.3390/antiox10071068 - 01 Jul 2021
Cited by 1 | Viewed by 2299
Abstract
Aging of oocytes and eggs diminishes their reproductive and developmental potential. It has been demonstrated previously that reactive oxygen species (ROS) contribute to accelerated aging of various cells. In the present study, we measured intracellular levels of ROS and investigated effects of several [...] Read more.
Aging of oocytes and eggs diminishes their reproductive and developmental potential. It has been demonstrated previously that reactive oxygen species (ROS) contribute to accelerated aging of various cells. In the present study, we measured intracellular levels of ROS and investigated effects of several selective antioxidants (AOXs) on the viability and functional activity of aging oocytes and eggs of the African clawed frog Xenopus laevis. The fluorescent cell-permeable dye DCFDA, which is widely employed for ROS detection in cultured mammalian cells, was used to monitor ROS levels in the fresh and bench-aged oocytes and eggs by an optimized protocol. It was found that intracellular ROS contents were increased in frog oocytes and eggs aged for 48 h. It was further demonstrated using selective cell-permeable AOXs targeting different ROS-generating mechanisms, that the major source of ROS in Xenopus oocytes and eggs is the plasma membrane NADPH oxidase, and that mitochondrial generation contributes to the intracellular ROS content to a lesser extent. Targeted inhibition of NADPH oxidase with a natural organic compound apocynin reduced ROS levels significantly in Xenopus oocytes and eggs, maintained their normal phenotype and supported their functional competence. To our knowledge this is the first report concerning beneficial effects of apocynin on the isolated gamete cells, such as oocytes and eggs. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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14 pages, 3780 KiB  
Article
Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia
by Ramona D’Amico, Tiziana Genovese, Marika Cordaro, Rosalba Siracusa, Enrico Gugliandolo, Alessio Filippo Peritore, Livia Interdonato, Rosalia Crupi, Salvatore Cuzzocrea, Rosanna Di Paola, Roberta Fusco and Daniela Impellizzeri
Antioxidants 2021, 10(7), 1014; https://doi.org/10.3390/antiox10071014 - 24 Jun 2021
Cited by 18 | Viewed by 3015
Abstract
Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which [...] Read more.
Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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17 pages, 3787 KiB  
Article
Transcriptome Analysis of Porcine Granulosa Cells in Healthy and Atretic Follicles: Role of Steroidogenesis and Oxidative Stress
by Li Meng, Zhenfang Wu, Kun Zhao, Jian Tao, Tam Chit, Shouquan Zhang, Chi Chiu Wang and Katja Teerds
Antioxidants 2021, 10(1), 22; https://doi.org/10.3390/antiox10010022 - 28 Dec 2020
Cited by 19 | Viewed by 3077
Abstract
One of the main causes of female infertility is a deregulated antral follicular atresia, a process of which the underlying molecular mechanisms are largely unknown. Our objective was therefore to characterize the complex transcriptome changes in porcine granulosa cells of healthy antral (HA) [...] Read more.
One of the main causes of female infertility is a deregulated antral follicular atresia, a process of which the underlying molecular mechanisms are largely unknown. Our objective was therefore to characterize the complex transcriptome changes in porcine granulosa cells of healthy antral (HA) and advanced antral atretic (AA) follicles, using ELISA and RNA-Seq followed by qRT-PCR and immunohistochemistry. Granulosa cell RNA-Seq data revealed 2160 differentially expressed genes, 1483 with higher and 677 with lower mRNA concentrations in AA follicles. Bioinformatic analysis showed that the upregulated genes in AA follicles were highly enriched in inflammation and apoptosis processes, while the downregulated transcripts were mainly highlighted in the steroid biosynthesis pathway and response to oxidative stress processes including antioxidant genes (e.g., GSTA1, GCLC, GCLM, IDH1, GPX8) involved in the glutathione metabolism pathway and other redox-related genes (e.g., RRM2B, NDUFS4). These observations were confirmed by RT-qPCR and immunohistochemistry. Additionally, the granulosa cells of AA follicles express significantly stronger 8-OHdG immunostaining, a marker of oxidative DNA damage, implicating that oxidative stress may participate in follicular atresia. We hypothesize that the decrease in anti-apoptotic factors and steroid hormones coincides with increased oxidative stress markers and the expression of pro-apoptotic factors, all contributing to antral follicular atresia. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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Review

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24 pages, 1469 KiB  
Review
Impact of Oxidative Stress on Male Reproduction in Domestic and Wild Animals
by Eliana Pintus and José Luis Ros-Santaella
Antioxidants 2021, 10(7), 1154; https://doi.org/10.3390/antiox10071154 - 20 Jul 2021
Cited by 57 | Viewed by 4895
Abstract
Oxidative stress occurs when the levels of reactive oxygen species (ROS) overcome the antioxidant defenses of the organism, jeopardizing several biological functions, including reproduction. In the male reproductive system, oxidative stress not only impairs sperm fertility but also compromises offspring health and survival, [...] Read more.
Oxidative stress occurs when the levels of reactive oxygen species (ROS) overcome the antioxidant defenses of the organism, jeopardizing several biological functions, including reproduction. In the male reproductive system, oxidative stress not only impairs sperm fertility but also compromises offspring health and survival, inducing oxidative damage to lipids, proteins and nucleic acids. Although a clear link between oxidative stress and male fertility disorders has been demonstrated in humans and laboratory rodents, little information is available about the implications of impaired redox homeostasis in the male fertility of domestic and wild animals. Therefore, this review aims to provide an update regarding the intrinsic and extrinsic factors that are associated with oxidative stress in the male reproductive system and their impact on the reproductive performance of domestic and wild animals. The most recent strategies for palliating the detrimental effects of oxidative stress on male fertility are reviewed together with their potential economic and ecological implications in the livestock industry and biodiversity conservation. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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Other

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13 pages, 2930 KiB  
Systematic Review
Toxicity of Antioxidant Supplements in Patients with Male Factor Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Massimiliano Creta, Davide Arcaniolo, Giuseppe Celentano, Luigi Napolitano, Roberto La Rocca, Marco Capece, Gianluigi Califano, Francesco Mangiapia, Lorenzo Spirito, Felice Crocetto, Ciro Imbimbo, Nicola Longo, Marco De Sio and Ferdinando Fusco
Antioxidants 2022, 11(1), 89; https://doi.org/10.3390/antiox11010089 - 30 Dec 2021
Cited by 6 | Viewed by 2167
Abstract
Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of antioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants [...] Read more.
Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of antioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants in infertile males. A systematic review was performed in March 2021. We included randomized controlled trials evaluating the incidence of adverse events in male patients with infertility receiving antioxidant therapy. Thirteen studies involving 1999 male patients were identified. Antioxidant supplementation in patients with male factor infertility was associated with a statistically significantly increased risk of nausea (Odds Ratio: 2.16, 95% Confidence Interval: 1.05–4.43, p = 0.036), headache (Odds Ratio: 3.05, 95% Confidence Interval: 1.59– 5.85 p = 0.001), and dyspepsia (Odds Ratio: 4.12, 95% Confidence Interval: 1.43–11.85, p = 0.009) compared to a placebo. Treatment discontinuation due to adverse events was not significantly higher in patients taking antioxidants compared to a placebo (Odds Ratio: 2.29, 95% Confidence Interval: 0.76–6.88, p = 0.139). When antioxidant supplementation is considered, a more accurate risk/benefit analysis is warranted. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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13 pages, 714 KiB  
Systematic Review
The Relationship between Seminal Fluid Hyperviscosity and Oxidative Stress: A Systematic Review
by Federica Barbagallo, Sandro La Vignera, Rossella Cannarella, Andrea Crafa, Aldo E. Calogero and Rosita A. Condorelli
Antioxidants 2021, 10(3), 356; https://doi.org/10.3390/antiox10030356 - 27 Feb 2021
Cited by 4 | Viewed by 4027
Abstract
Introduction: Seminal fluid viscosity is a key parameter to achieve fertilization. Viscosity is more frequently increased in patients with infertility. However, the mechanism by which hyperviscosity causes infertility is still poorly understood. As an increased blood viscosity is associated with diseases caused by [...] Read more.
Introduction: Seminal fluid viscosity is a key parameter to achieve fertilization. Viscosity is more frequently increased in patients with infertility. However, the mechanism by which hyperviscosity causes infertility is still poorly understood. As an increased blood viscosity is associated with diseases caused by oxidative stress, it can be supposed that there is a relationship between seminal fluid viscosity and oxidative stress in male infertility. Therefore, this systematic review aims to investigate the relationship between hyperviscous seminal fluid and oxidative stress. Materials and methods: We performed a systematic search on the following databases Pubmed, MEDLINE, Cochrane, and Scopus from the earliest available date to 10 January 2021, using Medical Subjects Headings (MeSH) indexes and keywords searches. The study included all the articles that evaluated the relationship between increased seminal fluid viscosity and oxidative stress. Article reviews even though dealing with seminal fluid hyperviscosity were excluded. Results: 5 articles were included in this systematic review. The results demonstrated an important impairment of antioxidant systems and increased oxidative stress in patients with high seminal fluid viscosity. Conclusions: These findings suggest that a careful assessment of oxidative stress in patients with hyperviscosity may be very useful in clinical practice. Infertile patients with seminal fluid hyperviscosity could benefit from the treatment with antioxidants to protect sperm cells from oxidative damage and to improve their functional properties. Full article
(This article belongs to the Special Issue Redox Signal in the Reproductive System)
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