Antioxidants

Editorial

Jump to: Research, Review

5 pages, 210 KiB

Open AccessEditorial

Mitochondria Biology in Reproductive Function

by Carla Tatone and Giovanna Di Emidio

Antioxidants 2022, 11(10), 1978; https://doi.org/10.3390/antiox11101978 - 4 Oct 2022

Cited by 3 | Viewed by 1524

Abstract

Mitochondria are multitasking organelles involved in the maintenance of cell homeostasis [...] Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

Research

Jump to: Editorial, Review

13 pages, 2405 KiB

Open AccessArticle

Resveratrol Treatment Induces Mito-miRNome Modification in Follicular Fluid from Aged Women with a Poor Prognosis for In Vitro Fertilization Cycles

by Rosalia Battaglia, Angela Caponnetto, Anna Maria Caringella, Anna Cortone, Carmen Ferrara, Salvatore Smirni, Rossana Iannitti, Michele Purrello, Giuseppe D’Amato, Bernard Fioretti and Cinzia Di Pietro

Antioxidants 2022, 11(5), 1019; https://doi.org/10.3390/antiox11051019 - 21 May 2022

Cited by 15 | Viewed by 3697

Abstract

Advanced maternal age impairs reproductive performance, influencing the quantity and the quality of oocytes. Mitochondria dysfunction seems to play a decisive role in conditioning the quality of the female gamete. Different in vitro and in vivo studies, demonstrated the antioxidant and anti-inflammatory activities [...] Read more.

Advanced maternal age impairs reproductive performance, influencing the quantity and the quality of oocytes. Mitochondria dysfunction seems to play a decisive role in conditioning the quality of the female gamete. Different in vitro and in vivo studies, demonstrated the antioxidant and anti-inflammatory activities of Resveratrol and its ability to improve mitochondria function even if the exact mechanism of action has not yet been demonstrated in human oocytes. In this paper, by retrospective analysis, we evaluated follicular fluid (FF) miRNome modification in aged women with a poor ovarian reserve receiving a resveratrol-based supplement the three months before the in vitro Fertilization (IVF) cycle. We found 13 differentially expressed microRNAs (miRNAs) in women treated with resveratrol and specifically miR-125b-5p, miR-132-3p, miR-19a-3p, miR-30a-5p and miR-660-5p, regulating mitochondrial proteins, are able to control metabolism and mitochondrial biogenesis. MiRNA expression differences, observed after resveratrol treatment in FF from women with a poor prognosis for IVF, demonstrated that resveratrol may act on mitomiRNAs to improve follicular microenvironment by transcriptomic and proteomic modifications in granulosa cells. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

13 pages, 3673 KiB

Open AccessArticle

Inhibitory Effects of 6,8-Diprenylorobol on Endometriosis Progression in Humans by Disrupting Calcium Homeostasis and Mitochondrial Function

by Jisoo Song, Gwonhwa Song, Sunwoo Park and Whasun Lim

Antioxidants 2022, 11(1), 171; https://doi.org/10.3390/antiox11010171 - 17 Jan 2022

Cited by 15 | Viewed by 2823

Abstract

6,8-Diprenylorobol is a flavonoid compound extracted from Cudrania tricuspidata. It has various biological functions, such as inhibiting melanin synthesis and inducting cell death in cancerous cells. In addition, Cudrania tricuspidata is known to be effective in female diseases, and previous studies have [...] Read more.

6,8-Diprenylorobol is a flavonoid compound extracted from Cudrania tricuspidata. It has various biological functions, such as inhibiting melanin synthesis and inducting cell death in cancerous cells. In addition, Cudrania tricuspidata is known to be effective in female diseases, and previous studies have shown anticancer effects in cervical cancer, a female reproductive disease. Outside of that, Cudrania tricuspidata has various physiological effects. However, the effect of 6,8-diprenylorobol is not well known in other benign and chronic diseases, even in endometriosis, which commonly arises in the female reproductive tract. In the present study, we determined the inhibitory effects of 6,8-diprenylorobol on the growth of endometriosis VK2/E6E7 and End1/E6E7 cells. Results indicated that 6,8-diprenylorobol suppressed cellular proliferation and increased the disruption of the cell cycle, mitochondrial membrane potential (MMP), generation of reactive oxygen species, and Ca²⁺ homeostasis in both endometriosis cells. However, the proliferation of normal stromal cells isolated from endometrial tissue was not altered by 6,8-diprenylorobol. The change in Ca²⁺ levels was estimated in fluo-4- or rhod-2-stained VK2/E6E7 and End1/E6E7 cells after the treatment of the intracellular calcium regulators 2-aminoethoxydiphenyl borate (2-APB) and ruthenium red (RUR) with 6,8-diprenylorobol. A combination of 6,8-diprenylorobol with each regulator decreased the calcium accumulation in endometriosis cells. Furthermore, Western blot analysis indicated that 6,8-diprenylorobol inactivated AKT pathways, whereas it activated P38 MAPK pathways. In addition, 6,8-diprenylorobol decreased mitochondrial respiration, leading to the reduction in ATP production in VK2/E6E7 and End1/E6E7 cells. Collectively, our results suggested that 6,8-diprenylorobol might be a potential therapeutic agent or adjuvant therapy for the management of endometriosis. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

24 pages, 2361 KiB

Open AccessArticle

Mitochondria Content and Activity Are Crucial Parameters for Bull Sperm Quality Evaluation

by Zofia E. Madeja, Marta Podralska, Agnieszka Nadel, Marcin Pszczola, Piotr Pawlak and Natalia Rozwadowska

Antioxidants 2021, 10(8), 1204; https://doi.org/10.3390/antiox10081204 - 27 Jul 2021

Cited by 19 | Viewed by 5503

Abstract

Standard sperm evaluation parameters do not enable predicting their ability to survive cryopreservation. Mitochondria are highly prone to suffer injuries during freezing, and any abnormalities in their morphology or function are reflected by a decline of sperm quality. Our work focused on describing [...] Read more.

Standard sperm evaluation parameters do not enable predicting their ability to survive cryopreservation. Mitochondria are highly prone to suffer injuries during freezing, and any abnormalities in their morphology or function are reflected by a decline of sperm quality. Our work focused on describing a link between the number and the activity of mitochondria, with an aim to validate its applicability as a biomarker of bovine sperm quality. Cryopreserved sperm collected from bulls with high (group 1) and low (group 2) semen quality was separated by swim up. The spermatozoa of group 1 overall retained more mitochondria (MitoTrackerGreen) and mtDNA copies, irrespective of the fraction. Regardless of the initial ejaculate quality, the motile sperm contained significantly more mitochondria and mtDNA copies. The same trend was observed for mitochondrial membrane potential (ΔΨm, JC-1), where motile sperm displayed high ΔΨm. These results stay in agreement with transcript-level evaluation (real-time polymerase chain reaction, PCR) of antioxidant enzymes (PRDX1, SOD1, GSS), which protect cells from the reactive oxygen species. An overall higher level of glutathione synthetase (GSS) mRNA was noted in group 1 bulls, suggesting higher ability to counteract free radicals. No differences were noted between basal oxygen consumption rate (OCR) (Seahorse XF Agilent) and ATP-linked respiration for group 1 and 2 bulls. In conclusion, mitochondrial content and activity may be used as reliable markers for bovine sperm quality evaluation. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

13 pages, 1938 KiB

Open AccessArticle

Low Doses of Resveratrol Protect Human Granulosa Cells from Induced-Oxidative Stress

by Beatriz Moreira-Pinto, Lia Costa, Eduarda Felgueira, Bruno M. Fonseca and Irene Rebelo

Antioxidants 2021, 10(4), 561; https://doi.org/10.3390/antiox10040561 - 4 Apr 2021

Cited by 24 | Viewed by 3962

Abstract

Resveratrol is a phytoalexin present in plant-derived foods, including grape’s skin, cocoa, and peanuts. Evidence suggests that it has beneficial effects on human health because of its antioxidant properties. However, there is limited knowledge about the part played by resveratrol in ovarian function. [...] Read more.

Resveratrol is a phytoalexin present in plant-derived foods, including grape’s skin, cocoa, and peanuts. Evidence suggests that it has beneficial effects on human health because of its antioxidant properties. However, there is limited knowledge about the part played by resveratrol in ovarian function. In this paper, the influence of resveratrol on granulosa cells (GC) was evaluated. In addition to being the main estradiol producers, GC are in direct contact with the oocyte, playing a fundamental role in its growth and development. The cell line COV434 and human granulosa cells (hGC), obtained from women undergoing assisted reproductive technology (ART), were used. GC were treated with resveratrol (0.001–20 μM) at different times (24–72 h). Low concentrations of this compound suggest a protective role, as they tend to reduce ROS/RNS formation after inducement of stress. On the contrary, high concentrations of resveratrol affect GC viability and steroidogenic function. As it may act as a direct modulator of GC oxidative balance, this work may help to clarify the impact of resveratrol on GC and the usefulness of this antioxidant as adjunct to infertility treatments. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Graphical abstract

18 pages, 3567 KiB

Open AccessArticle

Nicotinamide Supplementation Improves Oocyte Quality and Offspring Development by Modulating Mitochondrial Function in an Aged Caenorhabditis elegans Model

by Hyemin Min, Mijin Lee, Kyoung Sang Cho, Hyunjung Jade Lim and Yhong-Hee Shim

Antioxidants 2021, 10(4), 519; https://doi.org/10.3390/antiox10040519 - 26 Mar 2021

Cited by 20 | Viewed by 4062

Abstract

Aging is associated with a decline in the quality of biological functions. Among the aging processes, reproductive aging is a critical process because of its intergenerational effects. However, the mechanisms underlying reproductive aging remain largely unknown. Female reproductive aging is the primary reason [...] Read more.

Aging is associated with a decline in the quality of biological functions. Among the aging processes, reproductive aging is a critical process because of its intergenerational effects. However, the mechanisms underlying reproductive aging remain largely unknown. Female reproductive aging is the primary reason for limited fertility in mammals. Therefore, we attempted to investigate a modulator that can control female reproductive aging using a Caenorhabditis elegans model. In the present study, we examined the role of nicotinamide (NAM) in oocyte quality and offspring development. The levels of reactive oxygen species (ROS) and oxidative stress responses in aged oocytes, embryonic lethality, and developmental growth of the offspring were examined with maternal NAM supplementation. Supplementation with NAM improved oocyte quality, decreased embryonic lethality, and promoted germ cell apoptosis. Furthermore, NAM supplementation in aged mothers reduced ROS accumulation and improved mitochondrial function in oocytes. Consequently, the developmental growth and motility of offspring were improved. These findings suggest that NAM supplementation improves the health of the offspring produced by aged mothers through improved mitochondrial function. Taken together, our results imply that NAM supplementation in the aged mother improves oocyte quality and protects offspring by modulating mitochondrial function. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Graphical abstract

15 pages, 2376 KiB

Open AccessArticle

Modulation of Human Sperm Mitochondrial Respiration Efficiency by Plant Polyphenols

by Alessandra Ferramosca, Stefano Lorenzetti, Mariangela Di Giacomo, Paola Lunetti, Francesco Murrieri, Loredana Capobianco, Vincenza Dolce, Lamberto Coppola and Vincenzo Zara

Antioxidants 2021, 10(2), 217; https://doi.org/10.3390/antiox10020217 - 2 Feb 2021

Cited by 25 | Viewed by 3547

Abstract

Plant bioactives, such as polyphenols, can differentially affect (positively or negatively) sperm quality, depending on their concentration. These molecules have been proposed as natural scavengers of reactive oxygen species (ROS) for male infertility treatment. However, few data are available about their effects on [...] Read more.

Plant bioactives, such as polyphenols, can differentially affect (positively or negatively) sperm quality, depending on their concentration. These molecules have been proposed as natural scavengers of reactive oxygen species (ROS) for male infertility treatment. However, few data are available about their effects on the molecular mechanisms related to sperm quality and, in particular, to sperm mitochondrial function. We investigated the effects of quercetin, naringenin, genistein, apigenin, luteolin, and resveratrol at the concentration of 0.1–1000 nM on mitochondrial respiration efficiency. Upon chemical exposure, spermatozoa were swollen in a hypotonic solution and used for polarographic assays of mitochondrial respiration. All tested compounds, except for apigenin, caused a significant increase in the mitochondrial respiration efficiency at the concentration of 0.1 nM, and a significant decrease starting from concentrations of 10 nM. The analysis of oxygen consumption rate in the active and in the resting state of mitochondrial respiration suggested different mechanisms by which the tested compounds modulate mitochondrial function. Therefore, by virtue of their ability to stimulate the respiration active state, quercetin, genistein, and luteolin were found to improve mitochondrial function in asthenozoospermic samples. Our results are relevant to the debate on the promises and perils of natural antioxidants in nutraceutical supplementation. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

10 pages, 1632 KiB

Open AccessArticle

Mitochondrial Stress Response Gene Clpp Is Not Required for Granulosa Cell Function

by Ecem Esencan, Mauro Cozzolino, Gizem Imamoglu and Emre Seli

Antioxidants 2021, 10(1), 1; https://doi.org/10.3390/antiox10010001 - 22 Dec 2020

Cited by 10 | Viewed by 2541

Abstract

Mitochondrial unfolded protein response (UPR^mt) is a highly conserved mechanism, which is activated upon cellular or metabolic stress and aims to help cells maintain homeostasis. CLPP (caseinolytic peptidase P) plays a crucial factor for UPR^mt; it promotes the degradation [...] Read more.

Mitochondrial unfolded protein response (UPR^mt) is a highly conserved mechanism, which is activated upon cellular or metabolic stress and aims to help cells maintain homeostasis. CLPP (caseinolytic peptidase P) plays a crucial factor for UPR^mt; it promotes the degradation of unfolded mitochondrial proteins. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Here, we asked whether CLPP is necessary for granulosa/cumulus cell function. Clpp^flox/flox mice were generated and crossbred with Cyp19a1-Cre mice to generate mice with granulosa/cumulus cell-specific Clpp deletion (Clpp^−/−). Mature (8-week-old) Clpp^−/− female mice (8-week-old) were compared to same age wild type (WT) mice. We found that mature Clpp^−/− female mice were fertile and produced a similar number of pups per litter compared to WT. Folliculogenesis was not affected by the loss of CLPP in granulosa/cumulus cells as Clpp^−/− and WT mice had a similar number of primordial, primary, secondary, early antral, and antral follicles. The number of germinal vesicles (GV) and MII oocytes collected from Clpp^−/− and WT female mice were also similar. Our findings demonstrate that fertility in female mice is not affected by granulosa/cumulus cell-specific UPR^mt disruption through CLPP deletion. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

15 pages, 938 KiB

Open AccessArticle

Use of Parabens (Methyl and Butyl) during the Gestation Period: Mitochondrial Bioenergetics of the Testes and Antioxidant Capacity Alterations in Testes and Other Vital Organs of the F1 Generation

by Maria Manuel Oliveira, Fátima Martins, Mónica G. Silva, Elisete Correia, Romeu Videira and Francisco Peixoto

Antioxidants 2020, 9(12), 1302; https://doi.org/10.3390/antiox9121302 - 18 Dec 2020

Cited by 19 | Viewed by 3860

Abstract

Since the mid-1920s, parabens have been widely used as antimicrobial preservatives in processed foods and beverages, pharmaceuticals, and cosmetic products. Paraben use continues to generate considerable controversy, both in the general population and in the scientific community itself. The primary purpose of our [...] Read more.

Since the mid-1920s, parabens have been widely used as antimicrobial preservatives in processed foods and beverages, pharmaceuticals, and cosmetic products. Paraben use continues to generate considerable controversy, both in the general population and in the scientific community itself. The primary purpose of our study was to determine whether parabens (methyl and butyl at concentrations of 100 and 200 mg/kg body weight by subcutaneous injection) during pregnancy of adult female Wistar rats can have an impact on the F1 generation. As far as we know, we are the first to demonstrate that using parabens during pregnancy has negative repercussions on the mitochondrial bioenergetics and antioxidant activity of testicular germ cells in the F1 generation. Our study showed that there was a 48.7 and 59.8% decrease in the respiratory control index with 100 and 200 mg/kg of butylparaben, respectively. Cytochrome c oxidase activity was significantly inhibited (45 and 51%) in both groups. In addition, 200 mg/kg butylparaben promoted a marked decrease in citrate synthase activity, indicating that mitochondrial content decreased in the germ cells, especially spermatocytes and spermatids. Mitochondrial ROS production increased in groups exposed to parabens in a concentration-dependent manner, especially the butyl one (102 and 130%). The groups exposed to butylparaben showed an increase in superoxide dismutase (SOD) and catalase (CAT) activities, while glutathione reductase (GR) and glutathione S-transferase (GST) decreased. With methylparaben, only differences in SOD and GR were observed; for the latter, this only occurred with the highest concentration. The glutathione (GSH)/glutathione disulfide (GSSG) ratio did not undergo any significant change. However, there was a considerable increase in hydroperoxide content in animals exposed to butylparaben, with 100 and 200 mg/kg resulting in 98.6 and 188% increase, respectively. Furthermore, several other organs also showed alterations in antioxidant capacity due to paraben use. In summary, our study demonstrates that paraben use during pregnancy will cause severe changes in the mitochondrial bioenergetics and antioxidant capacity of testicular germ cells and the antioxidant capacity of several other F1 generation organs. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Graphical abstract

11 pages, 1611 KiB

Open AccessArticle

Relationship between the Length of Sperm Tail Mitochondrial Sheath and Fertility Traits in Boars Used for Artificial Insemination

by Karl Kerns, Jennifer Jankovitz, Julie Robinson, Amanda Minton, Chris Kuster and Peter Sutovsky

Antioxidants 2020, 9(11), 1033; https://doi.org/10.3390/antiox9111033 - 23 Oct 2020

Cited by 13 | Viewed by 4233

Abstract

The length of sperm tail midpiece, occupied by the mitochondrial sheath (MS), has been correlated with reproductive traits of mice, fish, and birds; however, it is not known whether such a correlation exists in higher order species such as domestic pigs. As the [...] Read more.

The length of sperm tail midpiece, occupied by the mitochondrial sheath (MS), has been correlated with reproductive traits of mice, fish, and birds; however, it is not known whether such a correlation exists in higher order species such as domestic pigs. As the mitochondria provide for sperm motility and generate the fertility-affecting reactive oxygen species (ROS), we hypothesized that MS length correlates with boar semen parameters and artificial insemination (AI) fertility. Sperm samples collected from 57 boars and used for single sire AI were labeled with ProteoStat Aggresome probe (AGG; Enzo Life Sciences) for MS imaging by epifluorescence microscopy and image-based flow cytometry (IBFC). The mean boar MS length was 7.26 ± 0.2 µm, ranging from 6.94 ± 0.18 µm to 7.65 ± 0.31 µm. The absolute longest MS measured was 9.19 µm and the shortest was 5.83 µm. Boars in the high tertile of MS length had significantly higher conception rate (CR; p = 0.05) and sperm parameters. Boars within the high tertile of average number piglets born per litter had significantly shorter MS and more varied MS length than boars in the low tertile (p = 0.04). MS length data correlated with conventional sperm parameters including percent viable and intact acrosomes (p = 0.03), basal:induced oxidation ratio (measure of intracellular ROS levels; p = 0.02) and Comp DNA (chromatin integrity; p = 0.06) along with many flow cytometric AGG parameters in IBFC. Sperm head AGG intensity median absolute deviation had a negative correlation with total born (r = −0.423 p = 0.004). These data reveal a complex relationship between sperm MS length and aggresome abundance to sperm parameters and boar reproductive success in AI service. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

17 pages, 1472 KiB

Open AccessReview

Carnitines as Mitochondrial Modulators of Oocyte and Embryo Bioenergetics

by Martina Placidi, Giovanna Di Emidio, Ashraf Virmani, Angela D’Alfonso, Paolo Giovanni Artini, Anna Maria D’Alessandro and Carla Tatone

Antioxidants 2022, 11(4), 745; https://doi.org/10.3390/antiox11040745 - 8 Apr 2022

Cited by 18 | Viewed by 3901

Abstract

Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit ROS production. Healthy oocyte mitochondria require a balance of pyruvate [...] Read more.

Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit ROS production. Healthy oocyte mitochondria require a balance of pyruvate and fatty acid oxidation. Transport of activated fatty acids into mitochondria requires carnitine. In this regard, the interest in the role of carnitines as mitochondrial modulators in oocyte and embryos is increasing. Carnitine pool includes the un-esterified l-carnitine (LC) and carnitine esters, such as acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC). In this review, carnitine medium supplementation for counteracting energetic and redox unbalance during in vitro culture and cryopreservation is reported. Although most studies have focused on LC, there is new evidence that the addition of ALC and/or PLC may boost LC effects. Pathways activated by carnitines include antiapoptotic, antiglycative, antioxidant, and antiinflammatory signaling. Nevertheless, the potential of carnitine to improve energetic metabolism and oocyte and embryo competence remains poorly investigated. The importance of carnitine as a mitochondrial modulator may suggest that this molecule may exert a beneficial role in ovarian disfunctions associated with metabolic and mitochondrial alterations, including PCOS and reproductive aging. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

26 pages, 28238 KiB

Open AccessReview

Mitochondrial Sirtuins in Reproduction

by Giovanna Di Emidio, Stefano Falone, Paolo Giovanni Artini, Fernanda Amicarelli, Anna Maria D’Alessandro and Carla Tatone

Antioxidants 2021, 10(7), 1047; https://doi.org/10.3390/antiox10071047 - 29 Jun 2021

Cited by 47 | Viewed by 5232

Abstract

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent [...] Read more.

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

10 pages, 936 KiB

Open AccessReview

Pathophysiology of Mitochondrial Dysfunction in Human Spermatozoa: Focus on Energetic Metabolism, Oxidative Stress and Apoptosis

by Chiara Castellini, Settimio D’Andrea, Giuliana Cordeschi, Maria Totaro, Antonio Parisi, Giovanna Di Emidio, Carla Tatone, Sandro Francavilla and Arcangelo Barbonetti

Antioxidants 2021, 10(5), 695; https://doi.org/10.3390/antiox10050695 - 28 Apr 2021

Cited by 41 | Viewed by 3964

Abstract

The dogma of mitochondria as the major source of energy in supporting sperm motility should be critically reconsidered in the light of several experimental data pointing to a major role of glycolysis in mammalian spermatozoa. In this light, the reported positive correlation between [...] Read more.

The dogma of mitochondria as the major source of energy in supporting sperm motility should be critically reconsidered in the light of several experimental data pointing to a major role of glycolysis in mammalian spermatozoa. In this light, the reported positive correlation between the mitochondrial membrane potential (ΔΨm) and motility of ejaculated spermatozoa cannot be explained convincingly by an impaired mitochondrial ATP generation only. Evidence has been produced suggesting that, in human sperm, dysfunctional mitochondria represent the main site of generation of reactive oxygen species (ROS). Furthermore, in these organelles, a complex bidirectional relationship could exist between ROS generation and apoptosis-like events that synergize with oxidative stress in impairing sperm biological integrity and functions. Despite the activity of enzymatic and non-enzymatic antioxidant factors, human spermatozoa are particularly vulnerable to oxidative stress, which plays a major role in male factor infertility. The purpose of this article is to provide an overview of metabolic, oxidative and apoptosis-like inter-linkages of mitochondrial dysfunction and their reflections on human sperm biology. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

24 pages, 2666 KiB

Open AccessReview

Mitochondrial Dysfunction and Oxidative Stress Caused by Cryopreservation in Reproductive Cells

by Roberto Gualtieri, Guruprasad Kalthur, Vincenza Barbato, Maddalena Di Nardo, Satish Kumar Adiga and Riccardo Talevi

Antioxidants 2021, 10(3), 337; https://doi.org/10.3390/antiox10030337 - 24 Feb 2021

Cited by 97 | Viewed by 8722

Abstract

Mitochondria, fundamental organelles in cell metabolism, and ATP synthesis are responsible for generating reactive oxygen species (ROS), calcium homeostasis, and cell death. Mitochondria produce most ROS, and when levels exceed the antioxidant defenses, oxidative stress (OS) is generated. These changes may eventually impair [...] Read more.

Mitochondria, fundamental organelles in cell metabolism, and ATP synthesis are responsible for generating reactive oxygen species (ROS), calcium homeostasis, and cell death. Mitochondria produce most ROS, and when levels exceed the antioxidant defenses, oxidative stress (OS) is generated. These changes may eventually impair the electron transport chain, resulting in decreased ATP synthesis, increased ROS production, altered mitochondrial membrane permeability, and disruption of calcium homeostasis. Mitochondria play a key role in the gamete competence to facilitate normal embryo development. However, iatrogenic factors in assisted reproductive technologies (ART) may affect their functional competence, leading to an abnormal reproductive outcome. Cryopreservation, a fundamental technology in ART, may compromise mitochondrial function leading to elevated intracellular OS that decreases sperm and oocytes’ competence and the dynamics of fertilization and embryo development. This article aims to review the role played by mitochondria and ROS in sperm and oocyte function and the close, biunivocal relationships between mitochondrial damage and ROS generation during cryopreservation of gametes and gonadal tissues in different species. Based on current literature, we propose tentative hypothesis of mechanisms involved in cryopreservation-associated mitochondrial dysfunction in gametes, and discuss the role played by antioxidants and other agents to retain the competence of cryopreserved reproductive cells and tissues. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

19 pages, 1092 KiB

Open AccessReview

Embryo and Its Mitochondria

by Pascale May-Panloup, Magalie Boguenet, Hady El Hachem, Pierre-Emmanuel Bouet and Pascal Reynier

Antioxidants 2021, 10(2), 139; https://doi.org/10.3390/antiox10020139 - 20 Jan 2021

Cited by 54 | Viewed by 5597

Abstract

The mitochondria, present in almost all eukaryotic cells, produce energy but also contribute to many other essential cellular functions. One of the unique characteristics of the mitochondria is that they have their own genome, which is only maternally transmitted via highly specific mechanisms [...] Read more.

The mitochondria, present in almost all eukaryotic cells, produce energy but also contribute to many other essential cellular functions. One of the unique characteristics of the mitochondria is that they have their own genome, which is only maternally transmitted via highly specific mechanisms that occur during gametogenesis and embryogenesis. The mature oocyte has the highest mitochondrial DNA copy number of any cell. This high mitochondrial mass is directly correlated to the capacity of the oocyte to support the early stages of embryo development in many species. Indeed, the subtle energetic and metabolic modifications that are necessary for each of the key steps of early embryonic development rely heavily on the oocyte’s mitochondrial load and activity. For example, epigenetic reprogramming depends on the metabolic cofactors produced by the mitochondrial metabolism, and the reactive oxygen species derived from the mitochondrial respiratory chain are essential for the regulation of cell signaling in the embryo. All these elements have also led scientists to consider the mitochondria as a potential biomarker of oocyte competence and embryo viability, as well as a key target for future potential therapies. However, more studies are needed to confirm these findings. This review article summarizes the past two decades of research that have led to the current understanding of mitochondrial functions in reproduction Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

24 pages, 2093 KiB

Open AccessReview

Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization

by Yoo-Jin Park and Myung-Geol Pang

Antioxidants 2021, 10(1), 98; https://doi.org/10.3390/antiox10010098 - 12 Jan 2021

Cited by 121 | Viewed by 11637

Abstract

Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, [...] Read more.

Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, sperm–egg interaction, and fertilization, excessive ROS generation is associated with male infertility. Moreover, mitochondria participate in diverse processes ranging from spermatogenesis to fertilization to regulate male fertility. This review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract). Moreover, mitochondria are also involved in testosterone production, regulation of proton secretion into the lumen to maintain an acidic condition in the epididymis, and sperm DNA condensation during epididymal maturation. We also established the new signaling pathway using previous proteomic data associated with male fertility, to understand the overall role of mitochondria in male fertility. The pathway revealed that male infertility is associated with a loss of mitochondrial proteins in spermatozoa, which induces low sperm motility, reduces OXPHOS activity, and results in male infertility. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Graphical abstract

19 pages, 1341 KiB

Open AccessReview

Mitochondrial Reactive Oxygen Species (ROS) Production Alters Sperm Quality

by Rosanna Chianese and Riccardo Pierantoni

Antioxidants 2021, 10(1), 92; https://doi.org/10.3390/antiox10010092 - 11 Jan 2021

Cited by 99 | Viewed by 6780

Abstract

Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic pathway, and the generation of reactive oxygen species (ROS). Despite the loss of the majority of the cytoplasm occurring during spermiogenesis, mammalian sperm [...] Read more.

Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic pathway, and the generation of reactive oxygen species (ROS). Despite the loss of the majority of the cytoplasm occurring during spermiogenesis, mammalian sperm preserves a number of mitochondria that rearrange in a tubular structure at the level of the sperm flagellum midpiece. Although sperm mitochondria are destroyed inside the zygote, the integrity and the functionality of these organelles seem to be critical for fertilization and embryo development. The aim of this review was to discuss the impact of mitochondria-produced ROS at multiple levels in sperm: the genome, proteome, lipidome, epigenome. How diet, aging and environmental pollution may affect sperm quality and offspring health—by exacerbating oxidative stress—will be also described. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

13 pages, 1455 KiB

Open AccessReview

The Impact of Unbalanced Maternal Nutritional Intakes on Oocyte Mitochondrial Activity: Implications for Reproductive Function

by Gemma Fabozzi, Benedetta Iussig, Danilo Cimadomo, Alberto Vaiarelli, Roberta Maggiulli, Nicolò Ubaldi, Filippo Maria Ubaldi and Laura Rienzi

Antioxidants 2021, 10(1), 91; https://doi.org/10.3390/antiox10010091 - 11 Jan 2021

Cited by 15 | Viewed by 4152

Abstract

Accumulating evidence on the effect of nutrition on reproduction is emerging from both animal and human studies. A healthy dietary pattern and nutrient supplementation, especially during the peri-conceptional period, might be helpful to achieve a live birth, although the mechanisms implicated are not [...] Read more.

Accumulating evidence on the effect of nutrition on reproduction is emerging from both animal and human studies. A healthy dietary pattern and nutrient supplementation, especially during the peri-conceptional period, might be helpful to achieve a live birth, although the mechanisms implicated are not fully understood. The endocrine system and the ooplasmic organelles apparatus, in particular the mitochondria, are clearly key elements during oogenesis and subsequent embryo development, and their proper functioning is associated with nutrition, even beyond maternal aging. Several studies in animal models have reported various adverse effects on mitochondria caused by unbalanced dietary intakes such as high fat diet, high fat high sugar diet, and low protein diet. The alterations produced might include mitochondrial intracellular distribution, content, structure, biogenesis, and functioning. This review summarizes the key role of mitochondria in female reproduction and the effects of different dietary macronutrient compositions on oocyte mitochondrial activity with their possible short-, medium-, and long-term effects. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

27 pages, 1791 KiB

Open AccessReview

Sirtuins—The New Important Players in Women’s Gynecological Health

by Ewa Maria Kratz, Izabela Kokot, Violetta Dymicka-Piekarska and Agnieszka Piwowar

Antioxidants 2021, 10(1), 84; https://doi.org/10.3390/antiox10010084 - 10 Jan 2021

Cited by 17 | Viewed by 3830

Abstract

The participation of sirtuins in the regulation of oxidative stress and inflammation lies at the basis of their possible modes of action and is related to their expression in various cell structures; their location in the mitochondria and blood plasma has been indicated [...] Read more.

The participation of sirtuins in the regulation of oxidative stress and inflammation lies at the basis of their possible modes of action and is related to their expression in various cell structures; their location in the mitochondria and blood plasma has been indicated as of primary importance. Despite many existing studies, research on sirtuins continues to present an opportunity to discover new functions and dependencies, especially when it comes to women’s gynecological health. Sirtuins have a significant role in both the formation and the course of many gynecological diseases. Their role is particularly important and well documented in the course of the development of cancer within the female reproductive organs; however, disturbances observed in the ovary and oocyte as well as in follicular fluid are also widely investigated. Additionally, sirtuins take part in some gynecological disturbances as regulative factors in pathways associated with insulin resistance, glucose and lipids metabolism disorders. In this review, we would like to summarize the existing knowledge about sirtuins in the manner outlined above. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

16 pages, 1776 KiB

Open AccessReview

Qualitative and Quantitative Ovarian and Peripheral Blood Mitochondrial DNA (mtDNA) Alterations: Mechanisms and Implications for Female Fertility

by Andrea Busnelli, Annalisa Navarra and Paolo Emanuele Levi-Setti

Antioxidants 2021, 10(1), 55; https://doi.org/10.3390/antiox10010055 - 5 Jan 2021

Cited by 12 | Viewed by 2832

Abstract

The reduction of female fertility over time is considered as a natural consequence of ovarian aging. The exact mechanism underlying this process is not fully elucidated. However, it is becoming increasingly evident that qualitative and quantitative mitochondrial genome alterations might play a relevant [...] Read more.

The reduction of female fertility over time is considered as a natural consequence of ovarian aging. The exact mechanism underlying this process is not fully elucidated. However, it is becoming increasingly evident that qualitative and quantitative mitochondrial genome alterations might play a relevant role. The former include mitochondrial DNA (mtDNA) damage caused by oxidative stress, the accumulation of acquired mtDNA mutations, the effects of inherited mtDNA mutations, and alterations in the mitochondrial stress response mechanism. The latter refer to alterations in the oocytes, granuolosa cells, and embryonic cells mtDNA content. The present review aims to investigate the evidence about: (1) the effect of qualitative and quantitative mtDNA alterations on female fertility, paying particular attention to those with a pathophysiology characterized by a relevant role of oxidative stress; (2) the use of oocytes, granulosa cells (GCs), embryonic cells, and peripheral blood cells mtDNA copy number as a female fertility surrogate biomarker; (3) experimental therapies tested to try to subvert the ovarian aging process with particular reference to antioxidant treatments. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Figure 1

29 pages, 1533 KiB

Open AccessReview

Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: A Review

by Cristina Rodríguez-Varela and Elena Labarta

Antioxidants 2020, 9(12), 1197; https://doi.org/10.3390/antiox9121197 - 28 Nov 2020

Cited by 60 | Viewed by 7217

Abstract

Mitochondria produce adenosine triphosphate (ATP) while also generating high amounts of reactive oxygen species (ROS) derived from oxygen metabolism. ROS are small but highly reactive molecules that can be detrimental if unregulated. While normally functioning mitochondria produce molecules that counteract ROS production, an [...] Read more.

Mitochondria produce adenosine triphosphate (ATP) while also generating high amounts of reactive oxygen species (ROS) derived from oxygen metabolism. ROS are small but highly reactive molecules that can be detrimental if unregulated. While normally functioning mitochondria produce molecules that counteract ROS production, an imbalance between the amount of ROS produced in the mitochondria and the capacity of the cell to counteract them leads to oxidative stress and ultimately to mitochondrial dysfunction. This dysfunction impairs cellular functions through reduced ATP output and/or increased oxidative stress. Mitochondrial dysfunction may also lead to poor oocyte quality and embryo development, ultimately affecting pregnancy outcomes. Improving mitochondrial function through antioxidant supplementation may enhance reproductive performance. Recent studies suggest that antioxidants may treat infertility by restoring mitochondrial function and promoting mitochondrial biogenesis. However, further randomized, controlled trials are needed to determine their clinical efficacy. In this review, we discuss the use of resveratrol, coenzyme-Q10, melatonin, folic acid, and several vitamins as antioxidant treatments to improve human oocyte and embryo quality, focusing on the mitochondria as their main hypothetical target. However, this mechanism of action has not yet been demonstrated in the human oocyte, which highlights the need for further studies in this field. Full article

(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Mitochondria Biology in Reproductive Function

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (21 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI