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Effect of Oxidative Stress on Reproduction and Development

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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: closed (31 May 2021) | Viewed by 46338

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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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is a growing amount of literature on the effects of oxidative stress resulting from the imbalance between pro-oxidants and antioxidants. Stressors, by inducing physiological and reproductive disorders, determine failures in various cellular processes, such as development, differentiation, growth, regeneration, and regression, threating 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 temperature fluctuations, osmotic stress, alterations in oxygen availability, and other anthropogenic impacts, all factors which can directly affect free radical chemistry during reproduction and development. Therefore, we cordially invite authors to contribute to this Special Issue with original research articles and reviews on how global warming, plastics, biofoulants, metals, etc. induce oxidative stress effects 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 conservation and sustainability, and indicate to us how we can perform assessments by oxidant and/or antioxidant detection.

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

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Keywords

free radicals and antioxidants;
oxidative stress;
endocrine disruption;
thermal fertility limit (TFL);
biodiversity conservation and sustainability;
hormones and vitamins;
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.

Published Papers (11 papers)

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Editorial

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3 pages, 195 KiB

Open AccessEditorial

Effect of Oxidative Stress on Reproduction and Development

by Giulia Guerriero and Gerardino D'Errico

Antioxidants 2022, 11(2), 312; https://doi.org/10.3390/antiox11020312 - 3 Feb 2022

Cited by 6 | Viewed by 1539

Abstract

There is a growing amount of literature on the effects of oxidative stress resulting from the imbalance between prooxidants and antioxidants [...] Full article

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

Research

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17 pages, 2699 KiB

Open AccessArticle

Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation

by Martin Alcala, Victoria E. Bolado, Isabel Sánchez-Vera, Sonia Clapés, Francisco Dasí, Guillermo Sáez, Esther Carrera, Fabiola Alvarez-Gallego, Mary R. Loeken and Marta Viana

Antioxidants 2021, 10(8), 1173; https://doi.org/10.3390/antiox10081173 - 23 Jul 2021

Cited by 3 | Viewed by 3289

Abstract

Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione content was also decreased, limiting the availability of this antioxidant in the embryos. Vitamin E supplementation efficiently maintained glutathione levels in the obese mothers, which could be used in their embryos to prevent oxidation-induced malformations. To test the effect of decreasing glutathione levels alone in a cell culture model of neuroepithelium, murine embryonic stem cells (ESC) were induced to form neuronal precursors and glutathione synthesis was inhibited with the gamma–glutamylcysteine synthesis inhibitor, buthionine sulfoximine (BSO). BSO inhibited the expression of Pax3, a gene required for neural tube closure that is also inhibited by oxidative stress. Taken together, our data indicate that obesity causes malformations through the depletion of maternal glutathione, thereby decreasing glutathione-dependent free radical scavenging in embryos, which can be prevented by vitamin E supplementation. Full article

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

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12 pages, 1253 KiB

Open AccessArticle

Diabetic Embryopathy Susceptibility in Mice Is Associated with Differential Dependence on Glucosamine and Modulation of High Glucose-Induced Oxidative Stress

by Jin Hyuk Jung and Mary R. Loeken

Antioxidants 2021, 10(8), 1156; https://doi.org/10.3390/antiox10081156 - 21 Jul 2021

Cited by 2 | Viewed by 2187

Abstract

The high K_M glucose transporter, GLUT2 (SLC2A2), is expressed by embryos and causes high rates of glucose transport during maternal hyperglycemic episodes in diabetic pregnancies and causes congenital malformations (diabetic embryopathy). GLUT2 is also a low K_M transporter of the amino sugar, glucosamine (GlcN), which enters the hexosamine biosynthetic pathway (HBP) and provides substrate for glycosylation reactions. Exogenous GlcN also increases activity of the pentose phosphate pathway (PPP), which increases production of NADPH reducing equivalents. GLUT2-transported GlcN is inhibited by high glucose concentrations. Not all mouse strains are susceptible to diabetic embryopathy. The aim of this study was to test the hypothesis that susceptibility to diabetic embryopathy is related to differential dependence on exogenous GlcN for glycosylation or stimulation of the PPP. We tested this using murine embryonic stem cell (ESC) lines that were derived from embryopathy-susceptible FVB/NJ (FVB), and embryopathy-resistant C57Bl/6J (B6), embryos in the presence of low or high glucose, and in the presence or absence of GlcN. There were no significant differences in Glut2 expression, or of glucose or GlcN transport, between FVB and B6 ESC. GlcN effects on growth and incorporation into glycoproteins indicated that FVB ESC are more dependent on exogenous GlcN than are B6 ESC. GlcN stimulated PPP activity in FVB but not in B6 ESC. High glucose induced oxidative stress in FVB ESC but not in B6 ESC. These results indicate that FVB embryos are more dependent on exogenous GlcN for glycosylation, but also for stimulation of the PPP and NADPH production, than are B6 embryos, thereby rendering FVB embryos more susceptible to high glucose to induce oxidative stress. Full article

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

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17 pages, 2627 KiB

Open AccessArticle

DNA Damage in Human Amniotic Cells: Antigenotoxic Potential of Curcumin and α-Lipoic Acid

by Filomena Mottola, Marianna Santonastaso, Concetta Iovine, Cristina Rossetti, Valentina Ronga and Lucia Rocco

Antioxidants 2021, 10(7), 1137; https://doi.org/10.3390/antiox10071137 - 17 Jul 2021

Cited by 7 | Viewed by 2370

Abstract

Oxidative imbalances in the gestational phase are responsible for certain complications during pregnancy and for foetal and neonatal genetic disorders. In this work, using human amniocytes, we aimed to evaluate the protection provided to foetal DNA by two concentrations of antioxidant molecules, α-lipoic acid (LA) and curcumin (Cur), against hydrogen peroxide (H₂O₂)-induced damage. Genotoxicity tests, performed by the random amplification of polymorphic DNA (RAPD-PCR) technique and TUNEL tests, showed that the lowest concentration of LA-protected cells and DNA from H₂O₂ insults. However, a greater ability to protect the amniocytes’ DNA against H₂O₂ was observed following co-treatment with the highest concentration of Cur with H₂O₂. In fact, a genomic template stability (GTS%) similar to that of the negative control and a statistically significant reduction in the DNA fragmentation index (DFI) were revealed. Moreover, following a combined treatment with both antioxidants and H₂O₂, no statistical difference from controls was observed, in terms of both induced mutations and DNA breaks. Furthermore, no effect on morphology or cell viability was observed. The results demonstrate the ability of LA and Cur to protect the genetic material of amniocytes against genotoxic insults, suggesting their beneficial effects in pathologies related to oxidative stress. Full article

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

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11 pages, 266 KiB

Open AccessArticle

Sperm Motility, Oxidative Status, and Mitochondrial Activity: Exploring Correlation in Different Species

by Alessandra Gallo, Maria Consiglia Esposito, Elisabetta Tosti and Raffaele Boni

Antioxidants 2021, 10(7), 1131; https://doi.org/10.3390/antiox10071131 - 16 Jul 2021

Cited by 34 | Viewed by 3359

Abstract

Sperm quality assessment is the first step for evaluating male fertility and includes the estimation of sperm concentration, motility, and morphology. Nevertheless, other parameters can be assessed providing additional information on the male reproductive potential. This study aimed to evaluate and correlate the oxidative status, mitochondrial functionality, and motility in spermatozoa of two marine invertebrate (Ciona robusta and Mytilus galloprovincialis) and one mammalian (Bos taurus) species. By combining fluorescent staining and spectrofluorometer, sperm oxidative status was evaluated through intracellular reactive oxygen species (ROS) and plasma membrane lipid peroxidation (LPO) analysis. Mitochondrial functionality was assessed through the mitochondrial membrane potential (MMP). In the three examined species, a negative correlation emerged between sperm motility vs ROS levels and LPO. Sperm motility positively correlated with MMP in bovine, whereas these parameters were not related in ascidian or even negatively related in mussel spermatozoa. MMP was negatively related to ROS and LPO levels in ascidians, only to LPO in bovine, and positively related in mussel spermatozoa. These results suggest that energy sources for sperm motility vary between species and that ROS causes a decline in sperm motility via oxidative damage of membrane lipids. Overall, this study validates the use of fluorescent probes in combination with spectrofluorometer as a simple and powerful methodology for supplementary evaluation of sperm quality shedding light on new potential quality markers and provided relevant information on sperm energetic metabolism. Full article

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

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15 pages, 2771 KiB

Open AccessFeature PaperArticle

N-acetyl-L-cysteine Improves the Developmental Competence of Bovine Oocytes and Embryos Cultured In Vitro by Attenuating Oxidative Damage and Apoptosis

by Wu-Sheng Sun, Hoon Jang, Mi-Ryung Park, Keon Bong Oh, Haesun Lee, Seongsoo Hwang, Li-Jie Xu, In-Sul Hwang and Jeong-Woong Lee

Antioxidants 2021, 10(6), 860; https://doi.org/10.3390/antiox10060860 - 27 May 2021

Cited by 9 | Viewed by 3280

Abstract

Oxidative stress has been suggested to negatively affect oocyte and embryo quality and developmental competence, resulting in failure to reach full term. In this study, we investigated the effect of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, on developmental competence and the quality of oocytes and embryos upon supplementation (0.1–10 mM) in maturation and culture medium in vitro using slaughterhouse-derived oocytes and embryos. The results show that treating oocytes with 1.0 mM NAC for 8 h during in vitro maturation attenuated the intracellular reactive oxygen species (ROS) (p < 0.05) and upregulated intracellular glutathione levels (p < 0.01) in oocytes. Interestingly, we found that NAC affects early embryonic development, not only in a dose-dependent, but also in a stage-specific, manner. Significantly (p < 0.05) decreased cleavage rates (90.25% vs. 81.46%) were observed during the early stage (days 0–2), while significantly (p < 0.05) increased developmental rates (38.20% vs. 44.46%) were observed during the later stage (from day 3) of embryonic development. In particular, NAC supplementation decreased the proportion of apoptotic blastomeres significantly (p < 0.05), resulting in enhanced hatching capability and developmental rates during the in vitro culture of embryos. Taken together, our results suggest that NAC supplementation has beneficial effects on bovine oocytes and embryos through the prevention of apoptosis and the elimination of oxygen free radicals during maturation and culture in vitro. Full article

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

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14 pages, 577 KiB

Open AccessArticle

The Impact of Early Pregnancy and Exposure to Tobacco Smoke on Blood Antioxidant Status and Copper, Zinc, Cadmium Concentration—A Pilot Study

by Anna Bizoń, Halina Milnerowicz, Katarzyna Kowalska-Piastun and Ewa Milnerowicz-Nabzdyk

Antioxidants 2021, 10(3), 493; https://doi.org/10.3390/antiox10030493 - 22 Mar 2021

Cited by 5 | Viewed by 2537

Abstract

The aim of the study was to evaluate the impact of early pregnancy and exposure to tobacco smoke on antioxidant status and copper, zinc, and cadmium concentrations in the blood of non-smoking and smoking, as well as non-pregnant or pregnant women. The study included 213 women. More specifically, 150 women in first trimester of pregnancy and 63 non-pregnant women. Women were divided into subgroups according to exposure to tobacco smoke. Pregnancy significant influences higher copper and lower zinc concentration in the serum, whereas exposure to tobacco smoke during pregnancy is mainly associated with an elevation in cadmium and zinc concentration. It seems that metallothionein, superoxide dismutase, and glutathione peroxidase are the important antioxidants during early pregnancy, when exposure to tobacco smoke occurs, whereas the pregnancy itself is associated with a higher concentration of metallothionein and activity of catalase. Both pregnancy in the first trimester and exposure to tobacco smoke decrease glutathione concentration. In addition, active and passive maternal smoking have a similarly negative effect on antioxidant status in the first trimester. Early pregnancy as well as exposure to tobacco smoke is associated with significant alteration in antioxidant status and copper, zinc, and cadmium concentration. Due to a small number of smoking subjects (11 cases of non-pregnant, active smokers and 14 pregnant active smokers), the obtained results should be treated as a pilot, and this should be considered for future studies. Full article

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

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17 pages, 2296 KiB

Open AccessArticle

Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium

by Naoko Kida, Yoshiyuki Matsuo, Yoshiko Hashimoto, Kenichiro Nishi, Tomoko Tsuzuki-Nakao, Hidemasa Bono, Tetsuo Maruyama, Kiichi Hirota and Hidetaka Okada

Antioxidants 2021, 10(1), 48; https://doi.org/10.3390/antiox10010048 - 3 Jan 2021

Cited by 10 | Viewed by 3939

Abstract

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling. Full article

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

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15 pages, 1962 KiB

Open AccessArticle

Composition of Royal Jelly (RJ) and Its Anti-Androgenic Effect on Reproductive Parameters in a Polycystic Ovarian Syndrome (PCOS) Animal Model

by Norhamidar Ab Hamid, Ainul Bahiyah Abu Bakar, Anani Aila Mat Zain, Nik Hazlina Nik Hussain, Zaidatul Akmal Othman, Zaida Zakaria and Mahaneem Mohamed

Antioxidants 2020, 9(6), 499; https://doi.org/10.3390/antiox9060499 - 7 Jun 2020

Cited by 18 | Viewed by 5277

Abstract

Royal jelly (RJ) has been shown to contribute its positive effects upon imbalance in the reproductive system. However, it remains unknown as to whether RJ has an anti-androgenic effect on reproductive parameters in a polycystic ovarian syndrome (PCOS) animal model. Composition of RJ was assessed by phytochemical screening and the LC–MS method. Forty immature female rats (3 weeks, 40–50 g) were randomly divided into five groups (n = 8 per group), i.e., control, testosterone (T), T+100RJ (100 mg/kg/day), T+200RJ (200 mg/kg/day RJ), and T+400RJ (400 mg/kg/day RJ) groups. Hyperandrogenism was induced by daily subcutaneous injection of T propionate for 3 weeks, followed by oral RJ for 4 weeks. The T+200RJ group had a significantly higher follicle-stimulating hormone level, and significantly lower luteinizing hormone, testosterone, and estradiol levels in comparison to the T group. Malondialdehyde level and glutathione peroxidase activity were significantly lower, while total antioxidant capacity level was significantly higher in the T+200RJ group compared to the T group. Histologically, the T+200RJ group showed recovery of various stages of ovarian follicular development. RJ at 200 mg/kg/day for 4 weeks significantly improved reproductive parameters in PCOS rats partly due to its anti-androgenic effect through antioxidant action and probably due to modulation on estrogenic activity, which needs further study to evaluate its exact mechanism of action. Full article

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

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Review

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20 pages, 604 KiB

Open AccessReview

Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols

by Maria Nunzia De Luca, Marisa Colone, Riccardo Gambioli, Annarita Stringaro and Vittorio Unfer

Antioxidants 2021, 10(8), 1283; https://doi.org/10.3390/antiox10081283 - 13 Aug 2021

Cited by 42 | Viewed by 6497

Abstract

Infertility is defined as a couple’s inability to conceive after at least one year of regular unprotected intercourse. This condition has become a global health problem affecting approximately 187 million couples worldwide and about half of the cases are attributable to male factors. Oxidative stress is a common reason for several conditions associated with male infertility. High levels of reactive oxygen species (ROS) impair sperm quality by decreasing motility and increasing the oxidation of DNA, of protein and of lipids. Multi-antioxidant supplementation is considered effective for male fertility parameters due to the synergistic effects of antioxidants. Most of them act by decreasing ROS concentration, thus improving sperm quality. In addition, other natural molecules, myo-inositol (MI) and d-chiro–inositol (DCI), ameliorate sperm quality. In sperm cells, MI is involved in many transduction mechanisms that regulate cytoplasmic calcium levels, capacitation and mitochondrial function. On the other hand, DCI is involved in the downregulation of steroidogenic enzyme aromatase, which produces testosterone. In this review, we analyze the processes involving oxidative stress in male fertility and the mechanisms of action of different molecules. Full article

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

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24 pages, 320 KiB

Open AccessReview

Oxidative Stress and BPA Toxicity: An Antioxidant Approach for Male and Female Reproductive Dysfunction

by Rosaria Meli, Anna Monnolo, Chiara Annunziata, Claudio Pirozzi and Maria Carmela Ferrante

Antioxidants 2020, 9(5), 405; https://doi.org/10.3390/antiox9050405 - 10 May 2020

Cited by 128 | Viewed by 9872

Abstract

Bisphenol A (BPA) is a non-persistent anthropic and environmentally ubiquitous compound widely employed and detected in many consumer products and food items; thus, human exposure is prolonged. Over the last ten years, many studies have examined the underlying molecular mechanisms of BPA toxicity and revealed links among BPA-induced oxidative stress, male and female reproductive defects, and human disease. Because of its hormone-like feature, BPA shows tissue effects on specific hormone receptors in target cells, triggering noxious cellular responses associated with oxidative stress and inflammation. As a metabolic and endocrine disruptor, BPA impairs redox homeostasis via the increase of oxidative mediators and the reduction of antioxidant enzymes, causing mitochondrial dysfunction, alteration in cell signaling pathways, and induction of apoptosis. This review aims to examine the scenery of the current BPA literature on understanding how the induction of oxidative stress can be considered the “fil rouge” of BPA’s toxic mechanisms of action with pleiotropic outcomes on reproduction. Here, we focus on the protective effects of five classes of antioxidants—vitamins and co-factors, natural products (herbals and phytochemicals), melatonin, selenium, and methyl donors (used alone or in combination)—that have been found useful to counteract BPA toxicity in male and female reproductive functions. Full article

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

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