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Effect of Oxidative Stress on Reproduction and Development—2nd Edition

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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: 31 December 2024 | Viewed by 10803

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Special Issue Editors

Dr. Giulia Guerriero

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Interdepartmental Research Center for Environment, IECEnv (CIRAm), University of Naples Federico II, 80134 Naples, Italy
Interests: climate change and reprotoxicity; antioxidative physiological defense; steroids and steroid receptors; antioxidants under steroid control; reproductive health assessment; endangered species and validation of non-destructive examination methods; biodiversity conservation microassay
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Prof. Dr. Gerardino D’Errico

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Department of Chemical Science, Complesso Monte S. Angelo, Via Cinthia 4, 80126 Naples, Italy
Interests: oxidative stress monitoring; reactive oxygen species; analytical and physico-chemical methods; electron paramagnetic resonance; non-invasive environmental monitoring; spectroscopic methods
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Special Issue Information

Dear Colleagues,

Our previous Special Issue on "Effect of Oxidative Stress on Reproduction and Development" (https://www.mdpi.com/journal/antioxidants/special_issues/oxidative_stress_reproduction), published in the 2021 volume of Antioxidants, received an overwhelming number of submissions and was a successful compilation of research and review articles. As this is a rapidly evolving topic, we would like to explore the role of oxidative stress in reproduction health further with a follow-up Special Issue for 2023–2024.

By inducing physiological and reproductive disorders, stressors determine failures in various cellular processes, such as development, differentiation, growth, regeneration, and regression, threatening the survival of the living species. Although a definite role of free radicals and antioxidants is well-established, there is sparse knowledge of their role in a multitude of stressors, such as climate change, temperature fluctuations, osmotic stress, alterations in oxygen availability, and other anthropogenic impacts, all factors that can directly affect free radical overexpression during reproduction. Therefore, we cordially invite authors to contribute to this Special Issue with original research articles and reviews on animal and vegetal reproduction. Critical and objective perspectives on hormones and vitamins and on factors that limit or facilitate fertility and fertilization also fall within the scope of this Special Issue. Data collected on this issue may represent a new opportunity to answer basic questions on one-health conservation and sustainability and indicate how we can perform assessments by oxidant and/or antioxidant detection.

Dr. Giulia Guerriero
Prof. Dr. Gerardino D’Errico
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

free radicals and antioxidants
oxidative stress
thermal fertility limit (TFL)
climate change
one-health
biodiversity conservation and sustainability
reproduction
development and nutrigenomics
methods for reactive oxygen species detection and antioxidant property determination
investigations on the mechanism of action of new antioxidants under steroid control

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Published Papers (7 papers)

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Research

19 pages, 6423 KiB

Open AccessArticle

Role of Anonychium africanum (Plantae, Fabaceae) in Metal Oxido-Inflammatory Response: Protection Evidence in Gonad of Male Albino Rat

by Harrison A. Ozoani, Orish Ebere Orisakwe, Costantino Parisi, Loredana Assisi, Anthonet N. Ezejiofor, Kenneth O. Okolo, Chinna N. Orish, Rubina Vangone, Emidio M. Sivieri and Giulia Guerriero

Antioxidants 2024, 13(9), 1028; https://doi.org/10.3390/antiox13091028 - 24 Aug 2024

Viewed by 801

Abstract

Male fertility is strongly affected by the overexpression of free radicals induced by heavy metals. The aim of this study was to evaluate the potential antioxidant, anti-inflammatory, and gonado-protective effects of natural compounds. Biochemical and morphological assays were performed on male albino rats divided into five groups: a control group (water only), a group orally exposed to a metal mixture of Pb-Cd-Hg-As alone and three groups co-administered the metal mixture and an aqueous extract of the Nigerian medicinal plant, Anonychium africanum (Prosopis africana, PA), at three different concentrations (500, 1000, and 1500 mg/kg) for 60 days. The metal mixture induced a significant rise in testicular weight, metal bioaccumulation, oxidative stress, and pro-inflammatory and apoptotic markers, while the semen analysis indicated a lower viability and a decrease in normal sperm count, and plasma reproductive hormones showed a significant variation. Parallel phytochemical investigations showed that PA has bioactive compounds like phlobatannins, flavonoids, polyphenols, tannins, saponins, steroids, and alkaloids, which are protective against oxidative injury in neural tissues. Indeed, the presence of PA co-administered with the metal mixture mitigated the toxic metals’ impact, which was determined by observing the oxido-inflammatory response via nuclear factor erythroid 2-related factor 2, thus boosting male reproductive health. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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18 pages, 7137 KiB

Open AccessArticle

Exogenous Oxidative Stress in Human Spermatozoa Induces Opening of the Mitochondrial Permeability Transition Pore: Effect on Mitochondrial Function, Sperm Motility and Induction of Cell Death

by Anita Bravo, Raúl Sánchez, Fabiola Zambrano and Pamela Uribe

Antioxidants 2024, 13(6), 739; https://doi.org/10.3390/antiox13060739 - 18 Jun 2024

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Abstract

Oxidative stress (OS) and disrupted antioxidant defense mechanisms play a pivotal role in the etiology of male infertility. The alterations in reactive oxygen species (ROS) production and calcium (Ca²⁺) homeostasis are the main activators for the mitochondrial permeability transition pore (mPTP) opening. The mPTP opening is one of the main mechanisms involved in mitochondrial dysfunction in spermatozoa. This alteration in mitochondrial function adversely affects energy supply, sperm motility, and fertilizing capacity and contributes to the development of male infertility. In human spermatozoa, the mPTP opening has been associated with ionomycin-induced endogenous oxidative stress and peroxynitrite-induced nitrosative stress; however, the effect of exogenous oxidative stress on mPTP opening in sperm has not been evaluated. The aim of this study was to determine the effect of exogenous oxidative stress induced by hydrogen peroxide (H₂O₂) on mPTP opening, mitochondrial function, motility, and cell death markers in human spermatozoa. Human spermatozoa were incubated with 3 mmol/L of H₂O₂ for 60 min, and intracellular Ca²⁺ concentration, mPTP opening, mitochondrial membrane potential (ΔΨm), ATP levels, mitochondrial reactive oxygen species (mROS) production, phosphatidylserine (PS) externalization, DNA fragmentation, viability, and sperm motility were evaluated. H₂O₂-induced exogenous oxidative stress caused increased intracellular Ca²⁺, leading to subsequent mPTP opening and alteration of mitochondrial function, characterized by ΔΨm dissipation, decreased ATP levels, increased mROS production, and the subsequent alteration of sperm motility. Furthermore, H₂O₂-induced opening of mPTP was associated with the expression of apoptotic cell death markers including PS externalization and DNA fragmentation. These results highlight the role of exogenous oxidative stress in causing mitochondrial dysfunction, deterioration of sperm motility, and an increase in apoptotic cell death markers, including PS externalization and DNA fragmentation, through the mPTP opening. This study yielded new knowledge regarding the effects of this type of stress on mitochondrial function and specifically on mPTP opening, factors that can contribute to the development of male infertility, considering that the role of mPTP in mitochondrial dysfunction in human sperm is not completely elucidated. Therefore, these findings are relevant to understanding male infertility and may provide an in vitro model for further research aimed at improving human sperm quality. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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13 pages, 6280 KiB

Open AccessArticle

Cytotoxic Oxidative Stress Effects of Neutrophil Extracellular Traps’ Components on Cattle Spermatozoa

by Rodrigo Rivera-Concha, Marion León, Aurora Prado-Sanhueza, Raúl Sánchez, Anja Taubert, Carlos Hermosilla, Pamela Uribe and Fabiola Zambrano

Antioxidants 2024, 13(6), 733; https://doi.org/10.3390/antiox13060733 - 17 Jun 2024

Viewed by 1246

Abstract

Bovine spermatozoa are highly susceptible to oxidative stress (OS), and it is known to affect their cellular functions. The main leukocyte producers of reactive oxygen species (ROS) in mammalian semen are polymorphonuclear neutrophils (PMN). PMN activation can result in the formation of neutrophil extracellular traps (NETs), which have been shown to affect the motility and function of spermatozoa. However, OS effects on bull spermatozoa derived from individual NETs components have not been investigated. The hypothesis of this study was that specific NETs components might generate OS on bull spermatozoa. Bovine sperm cells were incubated with five NETs-associated molecules, including 30 μg/mL histone 2A (H2A), neutrophil elastase (NE), 1 μg/mL myeloperoxidase (MPO), cathepsin G (Cat-G), and cathelicidin LL37 (LL-37), for a time course ranging from 15 to 240 min. Fluorescence microscopy was used to evaluate the coincubation of bovine PMN and sperm cells. Within 15 min, H2A, NE, and LL-37 caused membrane disruption, while MPO and Cat-G caused OS on bull spermatozoa after 1 h of coincubation. NET formation was observed within 15 min of coincubation in co-cultures of bovine PMN/sperm cells. This study is the first to report on the role of cytotoxic OS effects caused by NETs-derived components in bovine sperm in vitro. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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19 pages, 3161 KiB

Open AccessArticle

Vitamin C Alleviates the Negative Effects of Heat Stress on Reproductive Processes by Regulating Amino Acid Metabolism in Granulosa Cells

by Abdul Sammad, Tanveer Ahmed, Khair Ullah, Lirong Hu, Hanpeng Luo, Piniel Alphayo Kambey, Shah Faisal, Huabin Zhu, Yinxiong Li and Yachun Wang

Antioxidants 2024, 13(6), 653; https://doi.org/10.3390/antiox13060653 - 27 May 2024

Viewed by 2089

Abstract

Heat stress-induced biochemical alterations in ovarian follicles compromise the function of granulosa cells (GCs) and the developmental competence of oocytes. Summer heat stress can have a far-reaching negative impact on overall fertility and reproductive success. Together with the heat stress, the rise of assisted reproductive technologies (ART), potential confounding hazards of in vitro handling and the absence of systemic body support in ART makes it imperative to study the heat stress ameliorative effects of vitamin C under in vitro conditions. Using in vitro heat stress treatment of 43 °C for two hours in bovine GCs, we studied the effects of vitamin C on cell growth, oxidative stress, apoptosis and cell cycle progression together with a comprehensive metabolomics profiling. This study investigates the molecular milieu underlying the vitamin C (VC)-led alleviation of heat-related disruptions to metabolic processes in bovine GCs. The supplementation of VC ameliorated the detrimental effects of heat stress by reducing oxidative stress and apoptosis while restoring cell proliferation. Normal cell function restoration in treated GCs was demonstrated through the finding of significantly high levels of progesterone. We observed a shift in the metabolome from biosynthesis to catabolism, mostly dominated by the metabolism of amino acids (decreased tryptophan, methionine and tyrosine) and the active TCA cycle through increased Succinic acid. The Glutathione and tryptophan metabolism were important in ameliorating the inflammation and metabolism nexus under heat stress. Two significant enzymes were identified, namely tryptophan 2,3-dioxygenase (TDO2) and mitochondrial phenylalanyl-tRNA synthetase (FARS2). Furthermore, our findings provide insight into the significance of B-complex vitamins in the context of heat stress during VC supplementation. This study underscores the importance of VC supplementation in heat stress and designates multiple metabolic intervention faucets in the context of ameliorating heat stress and enhancing reproductive efficiency. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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18 pages, 807 KiB

Open AccessArticle

Micronutrient Antioxidants for Men (Menevit^®) Improve Sperm Function by Reducing Oxidative Stress, Resulting in Improved Assisted Reproductive Technology Outcomes

by Seiji Ogawa, Kuniaki Ota, Kaori Nishizawa, Masumi Shinagawa, Mikiko Katagiri, Hiroyuki Kikuchi, Hideyuki Kobayashi, Toshifumi Takahashi and Hiroaki Yoshida

Antioxidants 2024, 13(6), 635; https://doi.org/10.3390/antiox13060635 - 23 May 2024

Cited by 1 | Viewed by 1827

Abstract

Oxidative stress (OS) affects men’s health and impairs spermatogenesis. Micronutrient antioxidants are available for male infertility as complemental support; however, their efficacy remains debatable. This study aimed to investigate whether antioxidants can help to reduce sperm OS and improve semen analysis and quality. We included 171 male partners of couples planning to undergo assisted reproductive technology (ART). Male partners, aged 29–41 years, of couples intending to conceive were self-selected to take daily antioxidants (n = 84) containing folic acid and zinc, or not to take antioxidants (n = 52) for 6 months. We analyzed the alterations in serum oxidant levels, sperm parameters, OS, and deoxyribonucleic acid fragmentation after 3 and 6 months. Additionally, implantation, clinical pregnancy, and miscarriage rates after vitrified–warmed embryo transfer were compared between those taking antioxidants and those not taking them after 6 months. In men with high static oxidation–reduction potential (sORP), we observed a significant improvement in sperm concentration and sORP. The high-quality blastocyst rate tended to increase, and implantation and clinical pregnancy rates also significantly increased after 6 months of intervention. The micronutrient antioxidants could improve sperm function by reducing OS and improving ART outcomes. Therefore, micronutrient antioxidants may be a viable treatment option for male infertility. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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18 pages, 15335 KiB

Open AccessArticle

LanCL2 Implicates in Testicular Redox Homeostasis and Acrosomal Maturation

by Yanling Zhao, Jichen Wang, Shuai Shi, Xinting Lan, Xiangyu Cheng, Lixia Li, Yuanfeng Zou, Lanlan Jia, Wentao Liu, Qihui Luo, Zhengli Chen and Chao Huang

Antioxidants 2024, 13(5), 534; https://doi.org/10.3390/antiox13050534 - 27 Apr 2024

Cited by 1 | Viewed by 1158

Abstract

Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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26 pages, 7388 KiB

Open AccessArticle

Two-Generation Toxicity Study of the Antioxidant Compound Propyl-Propane Thiosulfonate (PTSO)

by Antonio Cascajosa-Lira, Remedios Guzmán-Guillén, Silvia Pichardo, Alberto Baños, Jose M. de la Torre, Nahum Ayala-Soldado, M. Rosario Moyano-Salvago, Isabel Ortiz-Jaraba, Ana M. Cameán and Angeles Jos

Antioxidants 2024, 13(3), 350; https://doi.org/10.3390/antiox13030350 - 15 Mar 2024

Cited by 1 | Viewed by 1634

Abstract

Propyl-propane thiosulfonate (PTSO), an antioxidant organosulfur compound present in the genus Allium, has become a potential natural additive for food and feed, as well as a possible biopesticide for pest control in plants. A toxicological assessment is necessary to verify its safety for livestock, consumers, and the environment. As part of the risk assessment of PTSO, this study was designed to explore its potential reproductive toxicity in mice following the OECD 416 guideline. The investigation spans two generations to comprehensively evaluate potential reproductive, teratogenic, and hereditary effects. A total of 80 CD1 mice per sex and generation were subjected to PTSO exposure during three phases (premating, gestation, and lactation). This evaluation encompassed three dose levels: 14, 28, and 55 mg PTSO/kg b.w./day, administered through the feed. No clinical changes or mortality attributed to the administration of PTSO were observed in the study. Some changes in the body weight and food consumption were observed, but not related to sex or in a dose-dependent manner. The two parental generations (F0, F1) exhibited normal reproductive performance, and the offspring (F1 and F2) were born without any abnormalities. The serum sexual hormone levels (progesterone -P-, testosterone -T-, estradiol -E2-, follicular stimulating hormone -FSH-, and luteinizing hormone -LH-) were in a normal range. Although significant changes were observed in the sperm analysis in the case of F0 group, no variation was found for F1 group, and no alterations in fertility were recorded either. The absolute organ weights and relative organ weight/body weight and organ weight/brain weight ratios, and the complete histopathological study, showed no significant alterations in males and females for all the generations considered. Considering all the results obtained, PTSO is not considered a reproductive or developmental toxicant in mice under the assayed conditions. These results support the good safety profile of PTSO for its potential application in the agrifood sector. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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