Mitochondria: their role in spermatozoa and in male infertility

Human Reproduction Update, Journal Year: 2021, Volume and Issue: 27(4), P. 697 - 719

Published: Jan. 8, 2021

Abstract BACKGROUND The best-known role of spermatozoa is to fertilize the oocyte and transmit paternal genome offspring. These highly specialized cells have a unique structure consisting all elements absolutely necessary each stage fertilization embryonic development. Mature are made up head with nucleus, neck, flagellum that allows motility contains midpiece mitochondrial helix. Mitochondria central cellular energy production but they also various other functions. Although mitochondria recognized as essential spermatozoa, their exact pathophysiological functioning complex. Available literature relative in dense contradictory some cases. Furthermore, only indirectly involved cytoplasmic heredity DNA, not transmitted descendants. OBJECTIVE AND RATIONAL This review aims summarize available on and, particular, respect humans, perspective better understanding anomalies could be implicated male infertility. SEARCH METHODS PubMed was used search MEDLINE database for peer-reviewed original articles reviews pertaining human mitochondria. Searches were performed using keywords belonging three groups: ‘mitochondria’ or ‘mitochondrial DNA’, ‘spermatozoa’ ‘sperm’ ‘reactive oxygen species’ ‘calcium’ ‘apoptosis’ signaling pathways’. combined relevant phrases. References from these obtain additional articles. OUTCOMES metabolism production, redox equilibrium calcium regulation, well apoptotic pathways, which flagellar motility, capacitation, acrosome reaction gametic fusion. In numerous cases, alterations one aforementioned functions linked decline sperm quality and/or link between appears more quantity mtDNA, existence large-scale deletions therein, inversely correlated quality, effects mutations seem heterogeneous particularly related pathogenicity. WIDER IMPLICATIONS importance reproduction, gamete has recently emerged following publications. Better infertility great interest current context where significant been observed.

Language: Английский

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Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(1), P. 42 - 42

Published: Jan. 8, 2021

Metformin (MF), a first-line drug to treat type 2 diabetes mellitus (T2DM), alone and in combination with other drugs, restores the ovarian function women polycystic ovary syndrome (PCOS) improves fetal development, pregnancy outcomes offspring health gestational (GDM) T2DM. MF treatment is demonstrated improve efficiency of vitro fertilization considered supplementary assisted reproductive technologies. administration shows positive effect on steroidogenesis spermatogenesis men metabolic disorders, thus indicates prospective use for improvement male functions fertility. lacks teratogenic effects has newborns. The review focused therapy restoration female endocrine disorders. mechanisms action are discussed, including normalization hormonal status PCOS, GDM, T2DM functional activity regulation gonadal axis.

Language: Английский

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Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: Dec. 9, 2022

Abstract Metformin, a biguanide drug, is the most commonly used first-line medication for type 2 diabetes mellites due to its outstanding glucose-lowering ability. After oral administration of 1 g, metformin peaked plasma concentration approximately 20–30 μM in 3 h, and then it mainly accumulated gastrointestinal tract, liver kidney. Substantial studies have indicated that exerts beneficial or deleterious effect by multiple mechanisms, apart from AMPK-dependent mechanism, also including several AMPK-independent such as restoring redox balance, affecting mitochondrial function, modulating gut microbiome regulating other signals, FBP1, PP2A, FGF21, SIRT1 mTOR. On basis these researchers tried repurpose this old drug further explored possible indications adverse effects metformin. Through investigating with clinical studies, concluded addition decreasing cardiovascular events anti-obesity, neurodegenerative disease, polycystic ovary syndrome, aging, cancer COVID-19, however, induces some effects, complaints, lactic acidosis, vitamin B12 deficiency, disease offspring impairment. Of note, dose much higher than clinically relevant dose, which may cast doubt on actual clinic. This review summarizes research developments mechanism action evidence discusses therapeutic potential safety.

Language: Английский

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The pleiotropic AMPK–CncC signaling pathway regulates the trade-off between detoxification and reproduction

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(10)

Published: Feb. 28, 2023

The association of decreased fecundity with insecticide resistance and the negative sublethal effects insecticides on insect reproduction indicates typical trade-off between two highly energy-demanding processes, detoxification reproduction. However, underlying mechanisms are poorly understood. energy sensor adenosine monophosphate-activated protein kinase (AMPK) transcription factor Cap "n" collar isoform C (CncC) important regulators metabolism xenobiotic response, respectively. In this study, using beetle Tribolium castaneum as a model organism, we found that deltamethrin-induced oxidative stress activated AMPK, which promoted nuclear translocation CncC through its phosphorylation. not only acts activator cytochrome P450 genes but also regulates expression coding for ecdysteroid biosynthesis juvenile hormone (JH) degradation enzymes, resulting in increased levels well JH titer vitellogenin (Vg) gene expression. These data show response to stress, pleiotropic AMPK-CncC signaling pathway mediates by up-regulating disturbing hormonal homeostasis.

Language: Английский

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Obesity‐induced oxidative stress and mitochondrial dysfunction negatively affect sperm quality

FEBS Open Bio, Journal Year: 2023, Volume and Issue: 13(4), P. 763 - 778

Published: March 3, 2023

Obesity is a systemic metabolic disease that can induce male infertility or subfertility through oxidative stress. The aim of this study was to determine how obesity impairs sperm mitochondrial structural integrity and function, reduces quality in both overweight/obese men mice on high‐fat diet (HFD). Mice fed the HFD demonstrated higher body weight increased abdominal fat content than those control diet. Such effects accompanied decline antioxidant enzymes, such as glutathione peroxidase (GPX) catalase superoxide dismutase (SOD) testicular epidydimal tissues. Moreover, malondialdehyde (MDA) significantly sera. Mature stress, including reactive oxygen species (ROS) levels decreased protein expression GPX1, which may impair reduce membrane potential (MMP) ATP production. cyclic AMPK phosphorylation status increased, whereas motility declined mice. Clinical studies being reduced SOD enzyme activity seminal plasma ROS sperm, by lower MMP low‐quality sperm. Furthermore, negatively correlated with increases BMI all clinical subjects. In conclusion, our results suggest excessive intake had similar disruptive structure well stress humans mice, turn induced motility. This agreement strengthens notion fat‐induced impaired function contribute subfertility.

Language: Английский

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The Beneficial Effect of Resveratrol on the Quality of Frozen-Thawed Boar Sperm

Animals, Journal Year: 2023, Volume and Issue: 13(18), P. 2829 - 2829

Published: Sept. 6, 2023

This study aimed to determine the effect of resveratrol and its optimal concentration on quality frozen-thawed (FT) boar sperm. Semen ejaculates were obtained from 13 Duroc boars aged between 1.5 3 years. The sperm sample was separated into 7 groups based concentrations in freezing extender, which 0 (control), 25, 50, 75, 100, 125, 250 µM, respectively. frozen using liquid nitrogen vapor thawed at 50 °C for 12 s. After thawing, total motility, progressive viability, intact acrosomes, mitochondrial membrane potential level MDA assessed. supplementation 50-100 µM improved motility viability FT comparison control group (p < 0.05). Furthermore, significantly more protective than terms acrosome, potential, Nonetheless, detrimental found a µM. In conclusion, addition extender is enhancing cryopreserved

Language: Английский

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Resveratrol Improves the Frozen-Thawed Ram Sperm Quality

Animals, Journal Year: 2023, Volume and Issue: 13(24), P. 3887 - 3887

Published: Dec. 18, 2023

Cryopreservation generates a substantial quantity of ROS in semen, leading to decline sperm quality and fertilization capacity. The objective this study was investigate the effects resveratrol its optimal concentration on ram after cryopreservation. Ram semen diluted with freezing medium containing different concentrations (0, 25, 50, 75, 100 μM). After thawing, various parameters such as total motility, progressive acrosome integrity, plasma membrane mitochondrial potential, glutathione (GSH) content, synthase (GPx) activity, superoxide dismutase (SOD) catalase (CAT) lipid peroxidation (LPO) malondialdehyde (MDA) level, SIRT1 DNA oxidative damage, AMPK phosphorylation level were assessed. In addition, post-thaw apoptosis evaluated. Comparatively, addition up 75 μM significantly improved motility cryopreserved sperm. Specifically, 50 demonstrated notable enhancement antioxidant capacity, adenosine triphosphate (ATP) levels compared control group (p < 0.05). It also 0.05) reduced damage DNA. However, detrimental observed at resveratrol. conclusion, cryopreservation solution is for enhancing

Language: Английский

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Role of Selective Autophagy in Spermatogenesis and Male Fertility

Cells, Journal Year: 2020, Volume and Issue: 9(11), P. 2523 - 2523

Published: Nov. 23, 2020

Autophagy is a “self-eating” process that engulfs cellular contents for their subsequent digestion in lysosomes to engage the metabolic need response starvation or environmental insults. According of degradation, autophagy can be divided into bulk (non-selective autophagy) and selective autophagy. Bulk degrades non-specific cytoplasmic materials nutrient while targets specific cargoes, such as damaged organelles, protein aggregates, intracellular pathogens. Selective has been documented relate reproductive processes, especially spermatogenesis, fertilization, biosynthesis testosterone. Although vital field reproduction, its role underlying mechanism have remained unclear. In this review, we focus on discuss recent advances our understanding spermatogenesis male fertility mammals. Understanding during will promote recognition genetic regulation infertility, shed light therapies infertile patients.

Language: Английский

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Integrated multi-omics analyses reveals molecules governing sperm metabolism potentially influence bull fertility

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 23, 2022

Bull fertility is of paramount importance in bovine industry because semen from a single bull used to breed several thousands cows; however, so far, no reliable test available for prediction. In the present study, spermatozoa high- and low-fertility bulls were subjected high-throughput transcriptomic, proteomic metabolomic analysis. Using an integrated multi-omics approach molecular differences between identified. We identified total 18,068 transcripts, 5041 proteins 3704 metabolites spermatozoa, which expression 4766 785 33 dysregulated bulls. At transcript level, genes involved oxidative phosphorylation pathway found be downregulated, while at protein level metabolic pathways significantly downregulated that Taurine hypotaurine metabolism Integrated analysis revealed interaction major pathways, including Butanoate metabolism, Glycolysis gluconeogenesis, Methionine cysteine Phosphatidyl inositol phosphate, pyrimidine saturated fatty acid beta oxidation. These findings collectively indicate molecules governing sperm potentially influence fertility.

Language: Английский

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Capacitation promotes a shift in energy metabolism in murine sperm

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 23, 2022

In mammals, sperm acquire fertilization ability after a series of physiological and biochemical changes, collectively known as capacitation, that occur inside the female reproductive tract. addition to other requirements, bioenergetic metabolism has been identified fundamental component in acquisition capacitation. Mammalian produce ATP through two main metabolic processes, oxidative phosphorylation (OXPHOS) aerobic glycolysis are localized different flagellar compartments, midpiece, principal piece, respectively. mouse sperm, occurrence many events associated with capacitation relies on activity these energy-producing pathways, leading hypothesis some may impose changes energetic demands. present study, we used extracellular flux analysis evaluate glycolytic respiratory parameters murine consequence Furthermore, examined whether variations affect sustainability. Our results show promotes shift usage ratio from glycolytic. However, this rewiring does not seem rate at which consume ATP. We conclude probable function switch is increase supply distal regions, thus sustaining demands arise

Language: Английский

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