Research

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18 pages, 2312 KiB

Open AccessArticle

Inhibition of Mitochondrial Uncoupling Proteins Arrests Human Spermatozoa Motility without Compromising Viability

by David F. Carrageta, Laís Freire-Brito, Bárbara Guerra-Carvalho, João C. Ribeiro, Bruno S. Monteiro, Alberto Barros, Pedro F. Oliveira, Mariana P. Monteiro and Marco G. Alves

Antioxidants 2023, 12(2), 409; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12020409 - 08 Feb 2023

Cited by 4 | Viewed by 2154

Abstract

Mitochondrial uncoupling proteins (UCPs) are central in the regulation of mitochondrial activity and reactive oxygen species (ROS) production. High oxidative stress is a major cause of male infertility; however, UCPs expression and function in human spermatozoa are still unknown. Herein, we aimed to [...] Read more.

Mitochondrial uncoupling proteins (UCPs) are central in the regulation of mitochondrial activity and reactive oxygen species (ROS) production. High oxidative stress is a major cause of male infertility; however, UCPs expression and function in human spermatozoa are still unknown. Herein, we aimed to assess the expression and function of the different homologs (UCP1-6) in human spermatozoa. For this purpose, we screened for the mRNA expression of all UCP homologs. Protein expression and immunolocalization of UCP1, UCP2, and UCP3 were also assessed. Highly motile spermatozoa were isolated from human normozoospermic seminal samples (n = 16) and incubated with genipin, an inhibitor of UCPs (0, 0.5, 5, and 50 µM) for 3 h at 37 °C. Viability and total motility were assessed. Mitochondrial membrane potential and ROS production were evaluated. Media were collected and the metabolic profile and antioxidant potential were analyzed by ¹H-NMR and FRAP, respectively. The expression of all UCP homologs (UCP1-6) mRNA by human spermatozoa is herein reported for the first time. UCP1-3 are predominant at the head equatorial segment, whereas UCP1 and UCP2 are also expressed at the spermatozoa midpiece, where mitochondria are located. The inhibition of UCPs by 50 µM genipin, resulting in the UCP3 inhibition, did not compromise sperm cell viability but resulted in irreversible total motility loss that persisted despite washing or incubation with theophylline, a cAMP activator. These effects were associated with decreased mitochondrial membrane potential and lactate production. No differences concerning UCP3 expression, however, were observed in spermatozoa from normozoospermic versus asthenozoospermic men (n = 6). The inhibition of UCPs did not increase ROS production, possibly due to the decreased mitochondrial activity and genipin antioxidant properties. In sum, UCPs are major regulators of human spermatozoa motility and metabolism. The discovery and characterization of UCPs’ role in human spermatozoa can shed new light on spermatozoa ROS-related pathways and bioenergetics physiology. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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15 pages, 3285 KiB

Open AccessArticle

Vitamin E Lipid-Based Nanodevices as a Tool for Ovine Sperm Protection against Oxidative Stress: Impact on Sperm Motility

by Alejandro Jurado-Campos, Pedro Javier Soria-Meneses, María Arenas-Moreira, Carlos Alonso-Moreno, Iván Bravo, Virginia Rodríguez-Robledo, Irene Sánchez-Ajofrín, Ana Josefa Soler, José Julián Garde and María del Rocío Fernández-Santos

Antioxidants 2022, 11(10), 1988; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11101988 - 06 Oct 2022

Cited by 5 | Viewed by 2138

Abstract

The advent of nanotechnology in the field of animal reproduction has led to the development of safer and more efficient therapies. The use of nanotechnology allows us to avoid the detrimental effects of certain traditional antioxidants, such as Vitamin E. Its hydrophobic nature [...] Read more.

The advent of nanotechnology in the field of animal reproduction has led to the development of safer and more efficient therapies. The use of nanotechnology allows us to avoid the detrimental effects of certain traditional antioxidants, such as Vitamin E. Its hydrophobic nature makes mandatory the use of organic solvents, which are toxic to sperm cells. This study aims to evaluate the efficiency of vitamin E nanoemulsions (NE) on ram (Ovis aries) spermatozoa. For this purpose, the effect of three NE concentrations (6, 12, and 24 mM) were assessed on sperm of 10 mature rams of the Manchega breed. Sperm samples were collected by artificial vagina, pooled, and diluted in Bovine Gamete Medium. The samples were stored at 37 °C and assessed at 0, 4, 8, and 24 h under oxidative stress conditions (100 µM Fe²⁺/ascorbate). Motility (CASA), viability (YO-PRO/IP), acrosomal integrity (PNA-FITC/IP), mitochondrial membrane potential (Mitotracker Deep Red 633), lipoperoxidation (C₁₁ BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA^®®) were assessed. A linear mixed-effects models were used to analyze the effects of time, NE, and oxidant (fixed factors) on sperm parameters, and a random effect on the male was also included in the model with Tukey’s post hoc test. Protection of ram spermatozoa with NE resulted in a more vigorous motility under oxidative stress conditions with respect Control and Free vitamin E, while preventing the deleterious effects of oxidative stress coming from the production of free radicals and lipid peroxidation. These results ascertain the high relevance of the use of delivery systems for sperm physiology preservation in the context of assisted reproduction techniques. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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14 pages, 1961 KiB

Open AccessArticle

Restoring Sperm Quality Post-Cryopreservation Using Mitochondrial-Targeted Compounds

by Macarena Gonzalez, Tanisha Prashar, Haley Connaughton, Michael Barry, Rebecca Robker and Ryan Rose

Antioxidants 2022, 11(9), 1808; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11091808 - 14 Sep 2022

Cited by 7 | Viewed by 2040

Abstract

While critical for male fertility preservation, cryopreservation damage reduces sperm quality and fertilization potential. This study investigated whether the addition of mitochondrial-targeted, antioxidant compounds, also known as Mitochondrial activators, to the cryopreservation medium could protect sperm quality during cryopreservation. For this, semen samples [...] Read more.

While critical for male fertility preservation, cryopreservation damage reduces sperm quality and fertilization potential. This study investigated whether the addition of mitochondrial-targeted, antioxidant compounds, also known as Mitochondrial activators, to the cryopreservation medium could protect sperm quality during cryopreservation. For this, semen samples from men undergoing IVF/ICSI treatment, which were donated for research, underwent cryopreservation in the absence or presence of BGP-15, MitoQ and L-carnitine. Fresh semen and thawed sperm samples from the same participant were analyzed for indicators of sperm quality: sperm viability, kinetics, mitochondrial reactive oxygen species (ROS) levels, Mitochondrial Membrane Potential (MMP) and DNA damage. Cryopreservation significantly reduced sperm viability and motility and predicted mucous penetration. BGP-15, MitoQ and L-carnitine improved sperm motility, whilst the addition of L-Carnitine prevented the loss of sperm viability during cryopreservation. Both BGP-15 and L-carnitine reduced sperm DNA oxidative damage, but only BGP-15 significantly reduced DNA fragmentation. More importantly, BGP-15 increased sperm predictive mucous penetration and MMP and reduced DNA oxidation. Our results show that the addition of BGP-15 or L-carnitine to the cryopreservation medium improves sperm quality post-thawing, highlighting the potential of mitochondrial antioxidants to improve long-term fertility preservation in males. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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13 pages, 956 KiB

Open AccessArticle

Sperm Quality Affected by Naturally Occurring Chemical Elements in Bull Seminal Plasma

by Filip Tirpák, Marko Halo, Marián Tomka, Tomáš Slanina, Katarína Tokárová, Martyna Błaszczyk-Altman, Lucia Dianová, Peter Ivanič, Róbert Kirchner, Agnieszka Greń, Norbert Lukáč and Peter Massányi

Antioxidants 2022, 11(9), 1796; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11091796 - 12 Sep 2022

Cited by 3 | Viewed by 2003

Abstract

This study monitored the chemical and biochemical composition of bovine seminal plasma (SP). Freshly ejaculated semen (n = 20) was aliquoted into two parts. The first aliquot was immediately assessed to determine the sperm motion parameters. Another motility measurement was performed following [...] Read more.

This study monitored the chemical and biochemical composition of bovine seminal plasma (SP). Freshly ejaculated semen (n = 20) was aliquoted into two parts. The first aliquot was immediately assessed to determine the sperm motion parameters. Another motility measurement was performed following an hour-long co-incubation of spermatozoa with SP at 6 °C. The other aliquot was processed to obtain the SP. Seminal plasma underwent the analyses of chemical composition and quantification of selected proteins, lipids and RedOx markers. Determined concentrations of observed parameters served as input data to correlation analyses where associations between micro and macro elements and RedOx markers were observed. Significant correlations of total oxidant status were found with the content of Cu and Mg. Further significant correlations of glutathione peroxidase were detected in relation to Fe and Hg. Furthermore, associations of chemical elements and RedOx markers and spermatozoa quality parameters were monitored. The most notable correlations indicate beneficial effects of seminal Fe on motility and Mg on velocity and viability of spermatozoa. On the contrary, negative correlations were registered between Zn and sperm velocity and seminal cholesterol content and motility. Our findings imply that seminal plasma has a prospective to be developed as the potential biomarker of bull reproductive health. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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25 pages, 5417 KiB

Open AccessArticle

Prophylactic and Ameliorative Effects of PPAR-γ Agonist Pioglitazone in Improving Oxidative Stress, Germ Cell Apoptosis and Inflammation in Gentamycin-Induced Testicular Damage in Adult Male Albino Rats

by Karima El-Sayed, Dina A. Ali, Shymaa Ahmed Maher, Dalia Ghareeb, Samy Selim, Sarah Albogami, Eman Fayad and Eman Kolieb

Antioxidants 2022, 11(2), 191; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020191 - 19 Jan 2022

Cited by 13 | Viewed by 2231

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is ubiquitously expressed in testicular tissue and plays a crucial role in regulating various physiological processes. Pioglitazone (PIO) is one of the PPAR-γ agonists, having anti-oxidant and anti-inflammatory effects. Patients on gentamycin treatment may undergo serious side effects [...] Read more.

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is ubiquitously expressed in testicular tissue and plays a crucial role in regulating various physiological processes. Pioglitazone (PIO) is one of the PPAR-γ agonists, having anti-oxidant and anti-inflammatory effects. Patients on gentamycin treatment may undergo serious side effects such as testicular damage. To the best of our knowledge, this was the first study to investigate the possible protective anti-inflammatory and anti-apoptotic effects of PIO on gentamycin-induced testicular damage. Fifty adult male Wistar albino rats included in the study as the control group (CTL) received normal saline; a gentamycin-induced testicular damage group (GM) received gentamycin (100 mg/kg); PIO5, PIO10, PIO20 groups received PIO at a dose of 5, 10, and 20 mg/ kg, respectively, for 21 days, and gentamycin was started at day 15 of the experiment for 6 days. The parameters of spermatozoa and histopathological alterations in the testes were significantly improved in the PIO20 group. Moreover, MDA levels, inflammatory mediators, and apoptotic Bax expression were decreased. The activity of glutathione peroxidase, catalase, total antioxidant capacity, and anti-apoptotic Bcl-2 genes expression were increased. It was concluded that PIO20 could protect against gentamycin-induced testicular damage in Wistar rats through its anti-oxidant, anti-inflammatory, and antiapoptotic effects. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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12 pages, 1403 KiB

Open AccessArticle

Measurement of Oxidative Stress Index in Seminal Plasma Can Predict In Vivo Fertility of Liquid-Stored Porcine Artificial Insemination Semen Doses

by Isabel Barranco, Camila P. Rubio, Asta Tvarijonaviciute, Heriberto Rodriguez-Martinez and Jordi Roca

Antioxidants 2021, 10(8), 1203; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081203 - 27 Jul 2021

Cited by 14 | Viewed by 3025

Abstract

The study evaluated the relation between the oxidative stress index (OSI) in porcine seminal plasma (n = 76) with sperm resilience and in vivo fertility (farrowing rate and litter size of 3137 inseminated sows) of liquid-stored artificial insemination (AI) semen doses. The [...] Read more.

The study evaluated the relation between the oxidative stress index (OSI) in porcine seminal plasma (n = 76) with sperm resilience and in vivo fertility (farrowing rate and litter size of 3137 inseminated sows) of liquid-stored artificial insemination (AI) semen doses. The OSI was assessed as the ratio of advanced oxidation protein products to Trolox-equivalent antioxidant capacity, both measured using an automated analyzer. Sperm motility (computer-assisted sperm analyzer) and viability (flow cytometry) were evaluated in semen AI-doses at 0 and 72 h of storage at 17 °C. Sperm resilience was defined as the difference between storage intervals. Semen AI-doses were hierarchically clustered as having high, medium and low seminal OSI (p < 0.001) with those of low displaying higher resilience (p < 0.01). Boars were hierarchically clustered into two groups (p < 0.001) as having either positive or negative farrowing rate and litter size deviation; the negative one showing higher seminal OSI (p < 0.05). In sum, seminal OSI was negatively related to sperm motility and the in vivo fertility of liquid-stored boar semen AI-doses, with the receiver operating characteristic curve presenting seminal OSI as a good predictive biomarker of in vivo fertility of AI-boars (area under the curve: 0.815, p < 0.05). Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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Review

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22 pages, 1060 KiB

Open AccessReview

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality

by Irma Virant-Klun, Senka Imamovic-Kumalic and Bojana Pinter

Antioxidants 2022, 11(8), 1617; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081617 - 20 Aug 2022

Cited by 25 | Viewed by 4193

Abstract

Exposure to endocrine-disrupting chemicals (EDCs) may result in oxidative stress and endocrine system disturbance, which can have an impact on human reproduction and development. In male reproductive health, EDCs have been related to impaired reproductive function and male infertility, altered fetal development, and [...] Read more.

Exposure to endocrine-disrupting chemicals (EDCs) may result in oxidative stress and endocrine system disturbance, which can have an impact on human reproduction and development. In male reproductive health, EDCs have been related to impaired reproductive function and male infertility, altered fetal development, and testicular germ-cell, prostate, and breast cancers. We conducted an electronic search using PubMed on endocrine disruptors related to oxidative stress and male infertility, and evaluated their association with endocrine-disrupting chemicals (bisphenols, phthalates, and parabens) in 25 articles. Higher levels of urinary bisphenols showed correlation with impaired semen quality and increased DNA damage. Considering phthalates and their metabolites, all studies found a positive association between urinary levels of phthalates and at least one semen parameter indicative of low semen quality; some studies also revealed sperm DNA damage. The studies on parabens less often revealed correlation of urinary parabens concentrations with a decrease in sperm count, as well as motility and DNA damage. Moreover, EDCs can elevate ROS production and lipid peroxidation, increase apoptosis, induce epigenetic modifications, and change the Y:X sperm chromosome ratio and sperm protein composition. Our review revealed detrimental effects of EDCs on semen quality and sperm DNA integrity—especially in BPA and phthalates, but also in parabens. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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22 pages, 1143 KiB

Open AccessReview

Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment

by Ashok Agarwal, Israel Maldonado Rosas, Christina Anagnostopoulou, Rossella Cannarella, Florence Boitrelle, Lina Villar Munoz, Renata Finelli, Damayanthi Durairajanayagam, Ralf Henkel and Ramadan Saleh

Antioxidants 2022, 11(3), 477; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11030477 - 28 Feb 2022

Cited by 39 | Viewed by 7240

Abstract

Oxidative stress (OS) due to an imbalance between reactive oxygen species (ROS) and antioxidants has been established as an important factor that can negatively affect the outcomes of assisted reproductive techniques (ARTs). Excess ROS exert their pathological effects through damage to cellular lipids, [...] Read more.

Oxidative stress (OS) due to an imbalance between reactive oxygen species (ROS) and antioxidants has been established as an important factor that can negatively affect the outcomes of assisted reproductive techniques (ARTs). Excess ROS exert their pathological effects through damage to cellular lipids, organelles, and DNA, alteration of enzymatic function, and apoptosis. ROS can be produced intracellularly, from immature sperm, oocytes, and embryos. Additionally, several external factors may induce high ROS production in the ART setup, including atmospheric oxygen, CO₂ incubators, consumables, visible light, temperature, humidity, volatile organic compounds, and culture media additives. Pathological amounts of ROS can also be generated during the cryopreservation-thawing process of gametes or embryos. Generally, these factors can act at any stage during ART, from gamete preparation to embryo development, till the blastocyst stage. In this review, we discuss the in vitro conditions and environmental factors responsible for the induction of OS in an ART setting. In addition, we describe the effects of OS on gametes and embryos. Furthermore, we highlight strategies to ameliorate the impact of OS during the whole human embryo culture period, from gametes to blastocyst stage. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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23 pages, 16238 KiB

Open AccessReview

Measuring Reactive Oxygen Species in Semen for Male Preconception Care: A Scientist Perspective

by Patience E. Castleton, Joshua C. Deluao, David J. Sharkey and Nicole O. McPherson

Antioxidants 2022, 11(2), 264; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020264 - 28 Jan 2022

Cited by 21 | Viewed by 7727

Abstract

Oxidative stress and elevated levels of seminal and sperm reactive oxygen species (ROS) may contribute to up to 80% of male infertility diagnosis, with sperm ROS concentrations at fertilization important in the development of a healthy fetus and child. The evaluation of ROS [...] Read more.

Oxidative stress and elevated levels of seminal and sperm reactive oxygen species (ROS) may contribute to up to 80% of male infertility diagnosis, with sperm ROS concentrations at fertilization important in the development of a healthy fetus and child. The evaluation of ROS in semen seems promising as a potential diagnostic tool for male infertility and male preconception care with a number of clinically available tests on the market (MiOXSYS, luminol chemiluminescence and OxiSperm). While some of these tests show promise for clinical use, discrepancies in documented decision limits and lack of cohort studies/clinical trials assessing their benefits on fertilization rates, embryo development, pregnancy and live birth rates limit their current clinical utility. In this review, we provide an update on the current techniques used for analyzing semen ROS concentrations clinically, the potential to use of ROS research tools for improving clinical ROS detection in sperm and describe why we believe we are likely still a long way away before semen ROS concentrations might become a mainstream preconception diagnostic test in men. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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