Melatonin rescues impaired penetration ability of human spermatozoa induced by mitochondrial dysfunction

Fertilization failure often occurs during in vitro fertilization (IVF) cycles despite apparently normal sperm and oocytes. Accumulating evidence suggests that mitochondria play crucial roles in the regulation of sperm function and male fertility. 3-Nitrophthalic acid (3-NPA) can induce oxidative stress in mitochondria, and melatonin, as an antioxidant, can improve mitochondrial function by reducing mitochondrial oxidative stress. The role of sperm mitochondrial dysfunction in fertilization failure during IVF is unclear. The present study revealed that spermatozoa with low, or poor, fertilization rates had swollen mitochondria, increased mitochondria-derived ROS, and attenuated mitochondrial respiratory capacity. 3-NPA treatment enhanced mitochondrial dysfunction in sperm. Spermatozoa with poor fertilization rates, and spermatozoa treated with 3-NPA, had reduced penetration ability. The concentration of melatonin was decreased in semen samples with low and poor fertilization rates. Melatonin, not only decreased excessive mitochondria-derived ROS, but also ‘rescued’ the reduced penetration capacity of spermatozoa treated with 3-NPA. Taken together, the study suggested that mitochondria-derived ROS and mitochondrial respiratory capacity are independent bio-markers for sperm dysfunction, and melatonin may be useful in improving sperm quality and overall male fertility.

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Antioxidants and Polyphenols: Concentrations and Relation to Male Infertility and Treatment Success

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/9140925 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Tali Silberstein ◽

Iris Har-Vardi ◽

Avi Harlev ◽

Michael Friger ◽

Batel Hamou ◽

...

Keyword(s):

Oxidative Stress ◽

Male Fertility ◽

Sperm Quality ◽

Treatment Success ◽

Sperm Concentration ◽

Infertility Treatment ◽

Fertility Treatment ◽

Fertilization Rates ◽

Total Antioxidant ◽

Antioxidant Concentration

Oxidative stress is induced by reactive oxygen substances (ROS) that are known to affect male fertility. The aims of this study were to prospectively investigate and characterize total antioxidant and specifically polyphenols concentrations and their relations to sperm quality and fertility treatment success. During their infertility treatment, sixty-seven males were prospectively recruited to this study. After separation of the sperm from the semen sample, the semen fluid samples antioxidants and polyphenols concentrations were determined. Antioxidant concentration was significantly associated with sperm concentration and total motile count. Antioxidants concentration in the group of male with sperm concentration ≥ 15 × 106was significantly higher than in the group of male with antioxidants concentration < 15 × 106(830.3 ± 350 μM and 268.3 ± 220 μM, resp.,p<0.001). Polyphenols concentration did not differ between the groups of sperm concentration above and below 15 × 106(178.7 ± 121 μM and 161.7 ± 61 μM, resp.,p-NS). No difference was found between fertilization rates and antioxidants or polyphenols concentrations. This is the first study that reports on polyphenols concentration within semen fluid. More studies are needed in order to investigate polyphenols role in male fertility.

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Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00159.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. E731-E739 ◽

Cited By ~ 81

Author(s):

Maria H. Holmström ◽

Eduardo Iglesias-Gutierrez ◽

Juleen R. Zierath ◽

Pablo M. Garcia-Roves

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Mitochondrial Dysfunction ◽

Mitochondrial Respiration ◽

Mitochondrial Dynamics ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Respiratory Capacity ◽

Tissue Specific ◽

Mitochondrial Respiratory

The tissue-specific role of mitochondrial respiratory capacity in the development of insulin resistance and type 2 diabetes is unclear. We determined mitochondrial function in glycolytic and oxidative skeletal muscle and liver from lean (+/ ?) and obese diabetic ( db/db) mice. In lean mice, the mitochondrial respiration pattern differed between tissues. Tissue-specific mitochondrial profiles were then compared between lean and db/db mice. In liver, mitochondrial respiratory capacity and protein expression, including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), was decreased in db/db mice, consistent with increased mitochondrial fission. In glycolytic muscle, mitochondrial respiration, as well as protein and mRNA expression of mitochondrial markers, was increased in db/db mice, suggesting increased mitochondrial content and fatty acid oxidation capacity. In oxidative muscle, mitochondrial complex I function and PGC-1α and mitochondrial transcription factor A (TFAM) protein levels were decreased in db/db mice, along with increased level of proteins related to mitochondrial dynamics. In conclusion, mitochondrial respiratory performance is under the control of tissue-specific mechanisms and is not uniformly altered in response to obesity. Furthermore, insulin resistance in glycolytic skeletal muscle can be maintained by a mechanism independent of mitochondrial dysfunction. Conversely, insulin resistance in liver and oxidative skeletal muscle from db/db mice is coincident with mitochondrial dysfunction.

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In vivo TNF-α inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00036.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. H1813-H1820 ◽

Cited By ~ 95

Author(s):

Gordon W. Moe ◽

Jose Marin-Garcia ◽

Andrea Konig ◽

Michael Goldenthal ◽

Xiangru Lu ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Left Ventricular ◽

Complex Iii ◽

Dna Fragments ◽

Respiratory Chain Enzyme ◽

Tnf Α ◽

Mitochondrial Respiratory

Heart failure is associated with increased myocardial expression of TNF-α. However, the role of TNF-α in the development of heart failure is not fully understood. In the present study, we investigated the contribution of TNF-α to myocardial mitochondrial dysfunction, oxidative stress, and apoptosis in a unique dog model of heart failure characterized by an activation of all of these pathological processes. Male mongrel dogs were randomly assigned ( n = 10 each) to 1) normal controls; 2) chronic pacing (250 beats/min for 4 wk) with concomitant administration of etanercept, a soluble p75 TNF receptor fusion protein, 0.5 mg/kg subcutaneously twice weekly; 3) chronic pacing with administration of saline vehicle. Mitochondrial function was assessed by left ventricular (LV) tissue mitochondrial respiratory enzyme activities. Oxidative stress was assessed with aldehyde levels, and apoptosis was quantified by photometric enzyme immunoassay for cytoplasmic histone-associated DNA fragments and terminal deoxynucleotide transferase-mediated nick-end labeling (TUNEL) assays. LV activity levels of mitochondrial respiratory chain enzyme complex III and V were reduced in the saline-treated dogs and restored either partially (complex III) or completely (complex V) in the etanercept-treated dogs. Aldehyde levels, DNA fragments, and TUNEL-positive cells were increased in the saline-treated dogs and normalized in etanercept-treated dogs. These changes were accompanied by an attenuation of LV dilatation and partial restoration of ejection fraction. Our data demonstrate that TNF-α contributes to progressive LV dysfunction in pacing-induced heart failure, mediated in part by a local impairment in mitochondrial function and increase in oxidative stress and myocyte apoptosis.

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Impact of Environmental and Lifestyle Use of Chromium on Male Fertility: Focus on Antioxidant Activity and Oxidative Stress

Antioxidants ◽

10.3390/antiox10091365 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1365 ◽

Cited By ~ 1

Author(s):

Sara C. Pereira ◽

Pedro F. Oliveira ◽

Sónia Rodrigues Oliveira ◽

Maria de Lourdes Pereira ◽

Marco G. Alves

Keyword(s):

Oxidative Stress ◽

Reproductive Health ◽

Male Fertility ◽

Sperm Quality ◽

Antioxidant Properties ◽

Chromium Picolinate ◽

Chromium Vi ◽

Valence States ◽

Chromium Compounds ◽

Male Reproductive Health

Male reproductive tissues are strongly susceptible to several environmental and lifestyle stressors. In general, male reproductive health is highly sensitive to oxidative stress, which results in reversible and/or irreversible changes in testosterone-producing cells, spermatogenesis, and sperm quality. Chromium compounds are widely used in the +3 and +6 valence states, as food supplements, and in the industrial field, respectively. Chromium (III) compounds, i.e., Cr(III)-tris-picolinate, [Cr(pic)3], known as chromium picolinate, are used as nutritional supplements for the control of diabetes, body weight, and muscular growth. However, previous studies showed that animal models exposed to chromium picolinate experienced degenerative changes in spermatogenesis. Contradictory results are documented in the literature and deserve discussion. Furthermore, the long-term effects of chromium picolinate on the antioxidant system of treated subjects have not been properly studied. Comprehensive studies on the role of this compound will help to establish the safe and useful use of chromium supplementation. On the other hand, chromium (VI) compounds are widely used in several industries, despite being well-known environmental pollutants (i.e., welding fumes). Chromium (VI) is known for its deleterious effects on male reproductive health as toxic, carcinogenic, and mutagenic. Previous studies have demonstrated severe lesions to mouse spermatogenesis after exposure to chromium (VI). However, workers worldwide are still exposed to hexavalent chromium, particularly in electronics and military industries. Data from the literature pinpoints mechanisms of oxidative stress induced by chromium compounds in somatic and germ cells that lead to apoptosis, thus underlining the impairment of fertility potential. In this review, we analyze the benefits and risks of chromium compounds on male fertility, as well as the mechanisms underlying (in)fertility outcomes. Although supplements with antioxidant properties may maximize male fertility, adverse effects need to be investigated and discussed.

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Review on the role of antioxidant supplementation against oxidative stress: a human and animal approach to male fertility

Research Society and Development ◽

10.33448/rsd-v11i1.25191 ◽

2022 ◽

Vol 11 (1) ◽

pp. e43211125191

Author(s):

Luana Nayara Gallego Adami ◽

Valter Luiz Maciel Junior ◽

João Diego Losano

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Male Fertility ◽

Sperm Quality ◽

Human Sperm ◽

Original Data ◽

Experimental Models ◽

Antioxidant Supplementation ◽

And Function

Male infertility is one important factor among the multifactorial causes of couple infertility, being oxidative stress one of the main related sources. Sperm is a specialized cell extremely susceptible to stress. To understand and mitigate this event, many studies have used different antioxidants, orally or in vitro supplementation, trying to improve sperm quality and function. Considering the extensive available literature regarding approaches and attempts to solve male fertility issues, the aim of this review is evaluating the effects of antioxidant supplementation on sperm, in both humans and experimental models with animals. This review selected original data from PubMed. The keywords used were: antioxidant, sperm, male fertility, antioxidant supplementation, male infertility; and the term "rodents" was added to the descriptors “antioxidant” and “male fertility”. Only studies published in indexed journals, in English, between 2015 and 2019 were included. This review involves i) human sperm and ii) rodent sperm. For the human approach, the search retrieved 496 articles and 80 were included, among which 28 studies were of in vitro antioxidant supplementation, 19 involved oral antioxidant supplementation and the remaining 33 concerned quantification of oxidants and antioxidants already present in the seminal samples. For the rodent approach, 152 articles were retrieved and 52 were included: 3 of varicocele, 11 of diabetes, 10 of therapeutic drugs, 3 of physical exercise, 10 of environmental exposure and 3 of heat stress. The remaining studies involved oxidative stress status in experimental models. Antioxidants use for reproductive purposes is increasing in an attempt to achieve better gametes and embryos. Vitamins C, B and E, selenium and zinc are the most commonly used antioxidants, with remarkable evidences in improving pathophysiological seminal conditions.

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Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols

Antioxidants ◽

10.3390/antiox10081283 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1283

Author(s):

Maria Nunzia De Luca ◽

Marisa Colone ◽

Riccardo Gambioli ◽

Annarita Stringaro ◽

Vittorio Unfer

Keyword(s):

Oxidative Stress ◽

Male Fertility ◽

Sperm Quality ◽

Synergistic Effects ◽

Steroidogenic Enzyme ◽

Transduction Mechanisms ◽

One Year ◽

Global Health Problem ◽

Male Factors

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.

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Zinc Transporter ZIP12 Maintains Zinc Homeostasis and Protects Spermatogonia From Oxidative Stress During Spermatogenesis

10.21203/rs.3.rs-800872/v1 ◽

2021 ◽

Author(s):

Xinye Zhu ◽

Chengxuan Yu ◽

Wangshu Wu ◽

Lei Shi ◽

Chenyi Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Male Fertility ◽

Sperm Quality ◽

Zinc Level ◽

Zinc Transporter ◽

Zinc Homeostasis ◽

Mouse Testis ◽

Zinc Transporters ◽

Wide Range

Abstract Background: Overwhelming evidences now suggest oxidative stress is a major cause of sperm dysfunction and male infertility. Zinc is an important non-enzyme antioxidant with a wide range of biological functions and plays a significant role in preserving male fertility. Notably, zinc trafficking through the cellular and intracellular membrane is endorsed by precise families of zinc transporters, i.e. SLC39s/ZIPs and SLC30s/ZnTs. However, the expression and function of zinc transporters in the male germ cells were rarely reported. The aim of this study is to determine the crucial zinc transporter responsible for the maintenance of spermatogenesis.Methods: In the present study, we investigated the expression of all fourteen ZIP members in mouse testis and further analyzed the characteristic of ZIP12 expression in testis and spermatozoa by qRT-PCR, immunoblot and immunohistochemistry analyses. To explore the antioxidant role of ZIP12 in spermatogenesis, an obese mouse model fed with high-fat-diet was employed to confirm the correlation between ZIP12 expression level and sperm quality. Furthermore, ZIP12 expression in response to oxidative stress in a spermatogonia cell line, C18-4 cells, was determined and its function involved in regulating cell viability and apoptosis was investigated by RNAi experiment. Results: We initially found that ZIP12 expression in mouse testis was significantly high compared to other members of ZIPs and its mRNA and protein were intensively expressed in testis rather than the other tissues. Importantly, ZIP12 was intensively abundant in spermatogonia and spermatozoa, both in mice and humans. Moreover, ZIP12 expression in testis significantly decreased in obese mice, which associated with reduced sperm zinc content, excessive sperm ROS, poor sperm quality and male subfertility. Similarly, its expression in C18-4 cells significantly declined in response to oxidative stress. Additionally, reduced ZIP12 expression by RNAi associated with a decline in zinc level subsequently caused low cell viability and high cell apoptosis in C18-4 cells. Conclusions: The zinc transporter ZIP12 is intensively expressed in testis, especially in spermatogonia and spermatozoa. ZIP12 may play a key role in maintaining intracellular zinc level in spermatogonia and spermatozoa, by which it resists oxidative stress during spermatogenesis and therefore preserves male fertility.

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Effect of new dietary supplement on sperm quality

Orvosi Hetilap ◽

10.1556/oh.2012.29468 ◽

2012 ◽

Vol 153 (45) ◽

pp. 1787-1792 ◽

Cited By ~ 1

Author(s):

Mária Horváth ◽

Endre Czeizel

Keyword(s):

Adverse Effect ◽

Clinical Trial ◽

Dietary Supplement ◽

Male Fertility ◽

Sperm Quality ◽

Sperm Count ◽

Before And After ◽

The Usa ◽

New Treatments

Introduction: There is a decline in male fertility thus new treatments are needed. Aims: To test the efficacy of a new dietary supplement developed in the USA and registered as a curing drug in Hungary (OGYI). Methods: In a clinical trial 100 men with low sperm quality (spermium count 5–20 M/ml, good motility 10–40%, and adverse shape 30–50%) were examined. Results: Sperm parameters were measured before and after a 3-month treatment and after another 3-month without treatment. This dietary supplement statistically and clinically significantly improved sperm count and motility. In 74 cases this dietary supplement demonstrated a beneficial effect on sperm quality (more than 10% increase in sperm count, or quality of motility, or shape); in 16 cases the improvement exceeded 30%. No adverse effect could be accounted for this treatment. Conclusions: This new dietary supplement may contribute to the treatment of male infertility. Orv. Hetil., 2012, 153, 1787–1792.

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