Dapagliflozin ameliorates diabetes-induced spermatogenic dysfunction by modulating the adenosine metabolism along the gut microbiota-testis axis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 5, 2024

Abstract Male infertility is one of the most common complications diabetes mellitus (DM). Dapagliflozin widely used to manage type II DM. This study aimed assess dapagliflozin’s effects on spermatogenesis by administering either dapagliflozin (Dapa) or vehicle (db) male db/db mice, and using littermate db/m mice as control (Con). We further performed integrative analyses cecal shotgun metagenomics, cecal/plasmatic/testicular metabolomics, testicular proteomics. found that treatment significantly alleviated diabetes-induced spermatogenic dysfunction improving sperm quality, including concentration motility. The overall microbial composition was reshaped in Dapa 13 species (such Lachnospiraceae bacterium 3–1) were regarded potential beneficial bacteria. Metabolites exhibited modified profiles, which adenosine, cAMP, 2′-deoxyinosine being notably altered cecum, plasma, testis, respectively. Testicular protein expression patterns similar between Con mice. In vivo results indicated when compared with db group, apoptosis oxidative stress testis tissues down-regulating 2′-deoxyinosine. validated vitro experiments GC-2 cells. Our findings support use prevent impaired quality treat diabetic infertility.

Language: Английский

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DNA Aptamer Raised against Advanced Glycation End Products Improves Sperm Concentration, Motility, and Viability by Suppressing Receptors for Advanced Glycation End Product-Induced Oxidative Stress and Inflammation in the Testes of Diabetic Mice

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5947 - 5947

Published: May 29, 2024

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules diabetic vascular complications. Here, we investigated effects of DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in T2DM mouse model. KK-Ay (DM) wild-type (non-DM) 4- 7-week-old mice were sacrificed to collect testes spermatozoa immunofluorescence, RT-PCR, histological analyses. DM non-DM subcutaneously infused with AGE-Apt or control-aptamer 6 weeks then sacrificed. Plasma glucose, AGEs, Rage gene expression 4-week-old plasma oxidative stress, pro-inflammatory expressions higher than those age-matched mice, latter which was associated seminiferous tubular dilation. did not affect glycemic parameters, it inhibited dilation, reduced number macrophages apoptotic cells, restored decrease concentration, motility, viability 13-week-old mice. Our findings suggest that AGEs-Apt may improve abnormality by suppressing AGE–RAGE-induced stress inflammation

Language: Английский

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Coenzyme Q10 and Melatonin for the Treatment of Male Infertility: A Narrative Review

Nutrients, Journal Year: 2022, Volume and Issue: 14(21), P. 4585 - 4585

Published: Nov. 1, 2022

Lifestyle and environmental factors can negatively impact fertility by means of oxidative stress. In this context, antioxidant supplementation therapy has gained much interest in recent years, different molecules, alone or combination, have been studied. The purpose the present review is to investigate evidence regarding efficacy coenzyme Q10 (CoQ10) melatonin on male infertility. A literature search using PUBMED database from 2000 October 2022 was performed explore role CoQ10 reproductive function. analysis involved a narrative synthesis. CoQ10, appears reduce testicular stress sperm DNA fragmentation improve parameters; particularly motility. Moreover, treatment associated with higher pregnancy rates, both naturally through assisted technology (ART). Larger studies are needed precisely determine its clinical efficacy. Melatonin known preclinical shown ability modulate function hormonal immune system regulation cell proliferation. Regardless, necessary assess potential

Language: Английский

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Human Sperm as an In Vitro Model to Assess the Efficacy of Antioxidant Supplements during Sperm Handling: A Narrative Review

Antioxidants, Journal Year: 2023, Volume and Issue: 12(5), P. 1098 - 1098

Published: May 15, 2023

Spermatozoa are highly differentiated cells that produce reactive oxygen species (ROS) due to aerobic metabolism. Below a certain threshold, ROS important in signal transduction pathways and cellular physiological processes, whereas overproduction damages spermatozoa. Sperm manipulation preparation protocols during assisted reproductive procedures—for example, cryopreservation—can result excessive production, exposing these oxidative damage. Thus, antioxidants relevant topic sperm quality. This narrative review focuses on human spermatozoa as an vitro model study which can be used supplement media. The comprises brief presentation of the structure, general overview main items reduction–oxidation homeostasis ambivalent relationship between ROS. body paper deals with studies have been test antioxidant compounds, including natural extracts. presence synergic effects different molecules could potentially lead more effective products and, future, vivo.

Language: Английский

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Oxidative Stress, Cytotoxic and Inflammatory Effects of Azoles Combinatorial Mixtures in Sertoli TM4 Cells

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1142 - 1142

Published: May 24, 2023

Triazole and imidazole fungicides are an emerging class of contaminants with increasing ubiquitous presence in the environment. In mammals, their reproductive toxicity has been reported. Concerning male reproduction, a combinatorial activity tebuconazole (TEB; triazole fungicide) econazole (ECO; compound) inducing mitochondrial impairment, energy depletion, cell cycle arrest, sequential activation autophagy apoptosis Sertoli TM4 cells (SCs) recently demonstrated. Given strict relationship between reactive oxygen species (ROS), causative role oxidative stress (OS) dysfunction, individual combined potential TEB ECO redox status alterations OS was investigated. Furthermore, considering impact cyclooxygenase (COX)-2 tumor necrosis factor-alpha (TNF-α) modulating fertility, protein expression levels were assessed. present study, we demonstrate that azoles-induced cytotoxicity is associated significant increase ROS production, drastic reduction superoxide dismutase (SOD) GSH-S-transferase levels, marked oxidized (GSSG) glutathione. Exposure to azoles also induced COX-2 increased TNF-α production. pre-treatment N-acetylcysteine (NAC) mitigates accumulation, attenuates rescues SCs from azole-induced apoptosis, suggesting ROS-dependent molecular mechanism underlying cytotoxicity.

Language: Английский

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