Oxidative Stress and Inflammation in the Pathogenesis of Reproductive Disorders

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 December 2022) | Viewed by 14280

Special Issue Editors


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Guest Editor
Physiology Unit, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP2, Bandar Saujana Putra, Jenjarom 42610, Selangor, Malaysia
Interests: infertility; oxidative stress; reproductive medicine; reproductive health; reproductive endocrinology; sperm biology; steroidogenesis; assisted reproductive techniques

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Guest Editor
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, SP2, Bandar Saujana Putra, Jenjarom 42610, Selangor, Malaysia
Interests: semen analysis; reproductive health; reactive oxygen species; inflammatory biomarkers; inflammation; immunology; immunomodulators; infection

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Guest Editor
Department of Life Science and Bioinformatics, Assam University, Silchar 788011, India
Interests: andrology; infertility; oxidative stress; reproductive toxicity; reproductive health; herbal management; human-assisted reproduction; environmental factors; environmental health

Special Issue Information

Dear Colleagues,

The pathophysiology of reproductive disorders is complicated by the presence of numerous interconnected endogenous pathways. Oxidative stress (OS) is the underlying core etiology for a wide range of health problems, including reproductive dysfunctions, as reported in both animals and humans. The endogenous antioxidant system is responsible for maintaining redox equilibrium of the reproductive system. OS prevails when the production of reactive oxygen species (ROS) exceeds the capacity of the endogenous antioxidant defense. As a result, antioxidant therapy is extremely important in the prevention and treatment of OS-mediated reproductive dysfunctions. Furthermore, inflammation is closely associated with OS and has the potential to set up a vicious cycle that may result in an exaggeration of tissue damage, germ cell apoptosis, disruption of normal reproductive functions, and development of a variety of reproductive disorders, eventually leading to infertility or subfertility. However, one of the major limitations of antioxidant therapy in the treatment of reproductive issues is the inability to identify specific medications that target both inflammation and OS at the same time—two of the most important pathways of disease pathogenesis in humans and animals. The current Special Issue will focus on the importance of advocating OS mitigation together with regulation of inflammatory reaction in various reproductive disorders.

Researchers across the globe are invited to submit their contributions (original articles, reviews, systematic reviews, meta-analyses, data manuscripts, commentary, or perspectives) relevant to the scope of the Special Issue as indicated by (but not limited to) the following keywords.

Dr. Pallav Sengupta
Dr. Sulagna Dutta
Dr. Shubhadeep Roychoudhury
Guest Editors

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Keywords

  •  antioxidants
  •  infertility
  •  oxidative stress
  •  reproductive disorder
  •  testicular dysfunction
  •  varicocele
  •  erectile dysfunction
  •  prostate cancer
  •  endometriosis
  •  Polycystic ovary syndrome (PCOS)
  •  spontaneous abortion
  •  recurrent pregnancy loss
  •  preeclampsia
  •  inflammation
  •  prostatitis
  •  epididymitis
  •  orchitis
  •  pelvic inflammatory disease
  •  Sexually transmitted infections (STIs)
  •  pre-term birth
  •  endothelial/uterine cancer
  •  cervical cancer
  •  ovarian cancer

Published Papers (6 papers)

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18 pages, 9904 KiB  
Article
Engineered Adipose-Derived Stem Cells Overexpressing RXFP1 via CRISPR Activation Ameliorate Erectile Dysfunction in Diabetic Rats
by Taotao Sun, Wenchao Xu, Bocheng Tu, Tao Wang, Jihong Liu, Kang Liu and Yang Luan
Antioxidants 2023, 12(1), 171; https://doi.org/10.3390/antiox12010171 - 11 Jan 2023
Cited by 4 | Viewed by 2145
Abstract
Due to the high incidence of diabetes mellitus (DM) and poor response to the first-line treatment of DM-induced erectile dysfunction (DMED), new therapeutic strategies for DMED are needed. Adipose-derived stem cell (ADSC) transplantation is considered a promising treatment modality for DMED but is [...] Read more.
Due to the high incidence of diabetes mellitus (DM) and poor response to the first-line treatment of DM-induced erectile dysfunction (DMED), new therapeutic strategies for DMED are needed. Adipose-derived stem cell (ADSC) transplantation is considered a promising treatment modality for DMED but is limited by poor survival and efficacy after transplantation. In this study, we aimed to increase the therapeutic effect of DMED by overexpressing the relaxin family peptide receptor 1 (RXFP1) using a clustered regularly interspaced short palindromic repeats activation (CRISPRa) system in ADSCs. Two lentiviruses carrying the CRISPRa system transfected ADSCs to overexpress RXFP1 (RXFP1-ADSCs). The intracavernous injection of ADSCs was performed in DMED rats induced by the intraperitoneal injection of streptozotocin. Four weeks after transplantation, we measured erectile function and collected specimens of the corpus cavernosum for follow-up detection. The results showed that ADSCs improved erectile function in diabetic rats, and the RXFP1-ADSCs were more significant. We detected reduced levels of oxidative stress, apoptosis and fibrosis together with relative normalization of endothelial and smooth muscle cell function in the penis after ADSC transplantation. RXFP1-ADSCs had more potent efficacy in the above alterations compared to negative control ADSCs due to the high levels of survival and paracrine capacity in RXFP1-ADSCs. The results revealed that RXFP1-ADSC transplantation could partially preserve erectile function in DMED rats associated with the regulation of oxidative stress, apoptosis, fibrosis and endothelial and smooth muscle cell dysfunction. RXFP1 may be the new target for the genetic modification of ADSCs, which benefits the management of DMED. Full article
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13 pages, 2247 KiB  
Article
NADPH Oxidase-Mediated Testicular Oxidative Imbalance Regulates the TXNIP/NLRP3 Inflammasome Axis Activation after Ischemia Reperfusion Injury
by Duaah Almarzouq and May Al-Maghrebi
Antioxidants 2023, 12(1), 145; https://doi.org/10.3390/antiox12010145 - 7 Jan 2023
Cited by 2 | Viewed by 2273
Abstract
Oxidative stress, inflammation and germ cell death are the main characteristics of testicular ischemia reperfusion injury (tIRI), which is considered as the underlying mechanism for testicular torsion and detorsion. The study aimed to examine the effect of tIRI-activated NADPH oxidase (NOX) on the [...] Read more.
Oxidative stress, inflammation and germ cell death are the main characteristics of testicular ischemia reperfusion injury (tIRI), which is considered as the underlying mechanism for testicular torsion and detorsion. The study aimed to examine the effect of tIRI-activated NADPH oxidase (NOX) on the expression of the NLRP3 inflammasome pathway components. Three groups of male Sprague–Dawley rats (n = 12 each) were studied: sham, unilateral tIRI only and tIRI treated with apocynin, a NOX-specific inhibitor. The tIRI rat model was subjected to 1 h of ischemia followed by 4 h of reperfusion. H&E staining, real time PCR, biochemical assays, and Western blot were utilized to evaluate spermatogenic damage, gene expression, oxidative stress markers, and NLRP3 pathway components, respectively. As a result of tIRI, decreased total antioxidant capacity and suppressed activities of superoxide dismutase and catalase were associated with spermatogenic arrest. The components of the NLRP3 inflammasome pathway (TXNIP, NLRP3, ASC, caspase-1, GSDMD, MMP-9) were upregulated transcriptionally and post-transcriptionally during tIRI. In parallel, tissue inflammation was demonstrated by a marked increase in the concentrations of myeloperoxidase, IL-1β, and IL-18. Apocynin treatment prevented testicular oxidative stress and inflammation. Thus, NOX inhibition by apocynin prevented ROS accumulation, proinflammatory cytokine overexpression and NLRP3 inflammasome activation during tIRI. Full article
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17 pages, 4490 KiB  
Article
Hesperidin Suppresses the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress and Disrupting Ca2+ Homeostasis
by Seon Ae Jeong, Changwon Yang, Jisoo Song, Gwonhwa Song, Wooyoung Jeong and Whasun Lim
Antioxidants 2022, 11(9), 1633; https://doi.org/10.3390/antiox11091633 - 23 Aug 2022
Cited by 12 | Viewed by 2499
Abstract
Although androgen deprivation therapy is mainly used for its treatment, the mortality rate of prostate cancer remains high due to drug resistance. Hence, there is a need to discover new compounds that exhibit therapeutic effects against prostate cancer with minimum side effects. Hesperidin [...] Read more.
Although androgen deprivation therapy is mainly used for its treatment, the mortality rate of prostate cancer remains high due to drug resistance. Hence, there is a need to discover new compounds that exhibit therapeutic effects against prostate cancer with minimum side effects. Hesperidin is a flavonoid carbohydrate isolated from citrus fruits. It has antiproliferative effects in various cancer types; however, whether it can modulate cell proliferation by modulating the key targets of cancer therapy, including intracellular signaling pathways and oxidative stress, remains unknown. Therefore, we confirmed that hesperidin suppressed the proliferation of prostate cancer cells, PC3 and DU145. Hesperidin induced cell death by regulating the cell cycle and inhibited the expression of proliferating cell nuclear antigen, a cell proliferation marker. Hesperidin also promoted the generation of reactive oxygen species and induced mitochondrial membrane depolarization and endoplasmic reticulum stress in prostate cancer cells. Moreover, as hesperidin increased Ca2+ levels in prostate cancer cells, we co-treated the inositol 1,4,5-trisphosphate receptor inhibitor, 2-aminoethyl diphenyl borate (2-APB), with hesperidin. Notably, 2-APB restored cell proliferation, which was reduced to control levels by hesperidin. In addition, hesperidin inhibited the activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways. Hesperidin also enhanced the anticancer effects of the chemotherapeutic agent, cisplatin, in both PC3 and DU145 cells. Taken together, these results suggest that hesperidin can be used as a potential therapeutic adjuvant in prostate cancer as it can inhibit cell proliferation by mediating oxidative stress and increasing Ca2+ levels. Full article
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9 pages, 1737 KiB  
Article
Association between Seminal Oxidation-Reduction Potential and Sperm DNA Fragmentation—A Meta-Analysis
by Manesh Kumar Panner Selvam, Saradha Baskaran, Samantha O’Connell, Wael Almajed, Wayne J. G. Hellstrom and Suresh C. Sikka
Antioxidants 2022, 11(8), 1563; https://doi.org/10.3390/antiox11081563 - 12 Aug 2022
Cited by 7 | Viewed by 2256
Abstract
Seminal oxidative stress and sperm DNA damage are potential etiologies of male factor infertility. The present study aims to evaluate the relationship between oxidation-reduction potential (ORP), a measure of oxidative stress, and sperm DNA fragmentation (SDF) by conducting a systematic review and meta-analysis [...] Read more.
Seminal oxidative stress and sperm DNA damage are potential etiologies of male factor infertility. The present study aims to evaluate the relationship between oxidation-reduction potential (ORP), a measure of oxidative stress, and sperm DNA fragmentation (SDF) by conducting a systematic review and meta-analysis of relevant clinical data. A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The COVIDENCE tool was used to screen and identify studies evaluating seminal ORP and SDF. Studies (n = 7) that measured seminal ORP and SDF of 3491 semen samples were included in the analysis. The fixed-effects model revealed a significant pooled correlation coefficient (r = 0.24; p < 0.001) between seminal ORP and SDF. Furthermore, subgroup analyses indicated that the pooled correlation coefficient between ORP and sperm chromatin dispersion (SCD) assay was less than other SDF assays (0.23 vs. 0.29). There was a moderate level of heterogeneity (I2 = 42.27%) among the studies, indicating a lack of publication bias. This is the first meta-analysis to reveal a positive correlation between seminal ORP and SDF. Furthermore, this study indicates the role of oxidative stress in the development of sperm DNA damage and thus warrants prospectively exploring the clinical value of these sperm function tests. Full article
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14 pages, 2821 KiB  
Article
Ginseng, Tribulus Extracts and Pollen Grains Supplementation Improves Sexual State, Testes Redox Status, and Testicular Histology in Nile Tilapia Males
by Abdallah Tageldein Mansour, Ahmed Saud Alsaqufi, Eglal Ali Omar, Hossam S. El-Beltagi, Tarek Mohamed Srour and Mokhtar Ibrahim Yousef
Antioxidants 2022, 11(5), 875; https://doi.org/10.3390/antiox11050875 - 29 Apr 2022
Cited by 7 | Viewed by 2457
Abstract
This study aimed to investigate the effect of dietary supplementation of three natural antioxidants on sex hormone levels, enzymatic and non-enzymatic antioxidant systems, and histological changes in the testes of male Nile tilapia, Oreochromis niloticus. A total of 210 male Nile tilapia [...] Read more.
This study aimed to investigate the effect of dietary supplementation of three natural antioxidants on sex hormone levels, enzymatic and non-enzymatic antioxidant systems, and histological changes in the testes of male Nile tilapia, Oreochromis niloticus. A total of 210 male Nile tilapia were distributed into seven treatments (three replicates for each) with an initial weight of 3.67 g fish−1. The fish were fed experimental diets (32% crude protein) without supplementation as control or supplemented with ginseng extract (GE; 0.2 and 0.4 g GE kg−1 diet), Tribulus terrestris extract (TT; 0.6 and 1.2 g TT kg−1 diet), and date palm pollen grains (DPPG; 3 and 6 g DPPG kg−1 diet) for 84 days. The results revealed a significant increase in the luteinizing hormone level with TT, DPPG, and GE supplementation increased the levels by 22.9%, 18.5%, and 17.6%, respectively. The testosterone level also increased significantly with TT1.2, GE0.4, TT0.6, and DPPG6 by 86.23%, 64.49%, 57.40%, and 24.62%, respectively. The antioxidant status in the testis homogenate showed a significant decrease in the level of thiobarbituric acid-reactive substances when using different dietary substances. In addition, glutathione reduced contents, glutathione S-transferases, glutathione peroxidase, catalase, and superoxide dismutase activities significantly increased with different dietary supplementation in a dose-dependent manner. The histological evaluation revealed normal histological features of the testes in all treatments with increasing active seminiferous tubules (%) in GE, TT, and DPPG supplemented groups, especially with the highest levels. In conclusion, the dietary supplementation of GE, TT, and DPPG enhanced sex hormones level, redox status, and testis structure and could improve the male reproductive performance of Nile tilapia. Full article
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18 pages, 1399 KiB  
Systematic Review
Association of Funisitis with Short-Term Outcomes of Prematurity: A Frequentist and Bayesian Meta-Analysis
by Tamara Maria Hundscheid, Maurice Jacob Huizing, Eduardo Villamor-Martinez, František Bartoš and Eduardo Villamor
Antioxidants 2023, 12(2), 534; https://doi.org/10.3390/antiox12020534 - 20 Feb 2023
Cited by 5 | Viewed by 1793
Abstract
The fetal systemic inflammatory response associated with intra-amniotic inflammation may play a key role in the pathogenesis of complications of preterm birth. Funisitis is the histologic equivalent of the fetal inflammatory response, whereas chorioamnionitis represents a maternal inflammatory response. We conducted a frequentist [...] Read more.
The fetal systemic inflammatory response associated with intra-amniotic inflammation may play a key role in the pathogenesis of complications of preterm birth. Funisitis is the histologic equivalent of the fetal inflammatory response, whereas chorioamnionitis represents a maternal inflammatory response. We conducted a frequentist and Bayesian model average (BMA) meta-analysis of studies investigating the effects of funisitis on short-term outcomes of prematurity. Thirty-three studies (12,237 infants with gestational age ≤ 34 weeks) were included. Frequentist meta-analysis showed that funisitis was associated with an increased risk of any bronchopulmonary dysplasia (BPD), moderate/severe BPD, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), any sepsis, early-onset sepsis (EOS), and mortality. However, Bayesian meta-analysis showed that the evidence in favor of the alternative hypothesis (i.e., funisitis is associated with an increased risk of developing the outcome) was strong for any IVH, moderate for severe IVH and EOS, and weak for the other outcomes. When the control group was restricted to infants having chorioamnionitis without funisitis, the only outcome associated with funisitis was any IVH. In conclusion, our data suggest that the presence of funisitis does not add an additional risk to preterm birth when compared to chorioamnionitis in the absence of fetal inflammatory response. Full article
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