Male obesity is associated with sperm telomere shortening and aberrant mRNA expression of autophagy-related genes.

BACKGROUND: Obesity is regarded a global public health crisis. It has been implicated in a variety of health problems, but when it comes to male fertility, how and to what extent obesity affects it are poorly understood. Accordingly, semen samples from 32 individuals with obesity (body mass index (BMI) ≥ 30 kg/m2) and 32 individuals with normal weight (BMI: 18.5-25 kg/m2) were obtained. Here, for the first time, we examined the association between obesity, relative sperm telomere length (STL) and autophagy-related mRNA levels such as Beclin1, AMPKa1, ULK1, BAX, and BCL2. Each group was also evaluated for conventional semen parameters, sperm apoptotic changes, DNA fragmentation index (DFI), sperm chromatin maturation, and reactive oxygen species (ROS) levels. RESULTS: Based on our findings, there was a marked reduction in relative STL in individuals with obesity as compared to the normal-weight group. We also found a significant negative correlation between relative STL and age, BMI, DFI, percentage of sperm with immature chromatin, and intracellular ROS levels in patients with obesity. In the normal-weight group, relative STL was only negatively correlated with DFI and intracellular ROS levels. Regarding mRNA expression, there was considerable upregulation of Beclin1, ULK1, and BCL2 in the group with obesity compared to the normal-weight group. Obesity was also found to be associated with a considerable decline in semen volume, total sperm count, progressive motility, and viability in comparison to normal-weight individuals. Furthermore, obesity was associated with considerably higher percentages of DFI, sperm with immature chromatin, late-stage apoptosis, and elevated ROS levels. CONCLUSION: According to our findings, obesity is associated with sperm telomere shortening and aberrant autophagy-related mRNA expression. It should be emphasized that telomere shortening in sperm may be an indirect consequence of obesity due to the oxidative stress associated with the condition. Nevertheless, further investigation is required for a more comprehensive understanding.

RéSUMé: CONTEXTE: L'obésité est considérée comme une crise mondiale de santé publique. Elle a été impliquée dans divers problèmes de santé ; mais quand il s'agit de la fertilité masculine, comment et dans quelle mesure l'obésité affecte cette fertilité restent mal compris. En conséquence, des échantillons de sperme de 32 hommes obèses (indice de masse corporelle (IMC) ≥ 30 kg/m²) et de 32 hommes ayant un poids normal (IMC : 18,5 à 25 kg/m²) ont été recueillis. A été examiné dans cette étude, pour la première fois, l'association entre l'obésité, la longueur relative des télomères des spermatozoïdes (LTS), et les taux d'ARNm liés à l'autophagie tels que Beclin1, AMPKa1, ULK1, BAX et BCL2. Chaque groupe a également été évalué pour les paramètres conventionnels du sperme, les changements apoptotiques des spermatozoïdes, l'indice de fragmentation de l'ADN (DFI), la maturation de la chromatine des spermatozoïdes et les niveaux d'espèces réactives de l'oxygène (ROS). RéSULTATS: Il y eut une réduction marquée de la LTS relative chez les hommes obèses par rapport à ceux du groupe de poids normal. Nous avons également trouvé une corrélation négative significative entre la LTS relative et l'âge, l'IMC, le DFI, le pourcentage de spermatozoïdes avec chromatine immature et les niveaux intracellulaires de ROS chez les hommes obèses. Dans le groupe d'hommes de poids normal, la LTS relative n'était corrélée négativement qu'avec les taux de DFI et de ROS intracellulaires. En ce qui concerne l'expression de l'ARNm, il y avait une régulation positive considérable de Beclin1, ULK1 et BCL2 dans le groupe d'hommes obèses par rapport à ceux du  groupe de poids normal. L'obésité s'est également avérée être associée à une baisse considérable du volume de sperme, du nombre total de spermatozoïdes, de la mobilité progressive et de la viabilité des spermatozoïdes par rapport aux hommes de poids normal. En outre, l'obésité était associée à des pourcentages considérablement plus élevés de DFI, de spermatozoïdes avec chromatine immature, d'apoptose à un stade avancé, et de niveaux élevés de ROS. CONCLUSION: Selon nos résultats, l'obésité est associée au raccourcissement des télomères des spermatozoïdes et à une expression aberrante d'ARNm liés à l'autophagie. Il convient de souligner que le raccourcissement des télomères dans les spermatozoïdes peut être une conséquence indirecte de l'obésité en raison du stress oxydatif associé à la maladie. Néanmoins, des études plus approfondies sont nécessaires pour une compréhension plus complète.

Therapeutic Effects of Edaravone on Azoospermia: Free Radical Scavenging and Autophagy Modulation in Testicular Tissue of Mice.

Background: Chemotherapeutic agents such as cyclophosphamide and busulfan have been shown to have a negative impact on the spermatogenesis process. Based on this fact, the objective of this study was to investigate the effects of edaravone on spermatogenesis in busulfan-induced mice. Methods: Forty adult male mice were equally divided into the four groups: 1) control, 2) edaravone, 3) busulfan, and 4) busulfan + edaravone. Then, the sperm parameters, histopathological examinations, and serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also assessed. Caspase-3, Beclin-1, and ATG-7 mRNA levels were also determined using real-time PCR. Results: Our results revealed that treatment of mice with edaravone in busulfan-induced azoospermia significantly improves sperm parameters, including total count, morphology, and viability (p<0.05). Furthermore, edaravone administration led to a significant increase in serum testosterone (p<0.0001) and FSH (p<0.001) levels, as well as testis weight (p<0.05) and volume (p<0.01). Edaravone also prevented a decrease in the number of testicular cells including spermatogonia (p<0.0001), primary spermatocytes (p<0.001), round spermatids (p<0.0001), Sertoli (p<0.01), and Leydig cells (p<0.0001) in busulfan-treated mice. Additionally, in busulfan-induced azoospermia, edaravone significantly reduced the percentage of sperm with immature chromatin (p<0.0001). Following treatment with edaravone, a decrease in reactive oxygen species (ROS) and an increase in glutathione (GSH) production were noted compared to busulfan-treated mice. Furthermore, caspase-3 (p<0.05), Beclin-1, and ATG-7 (p<0.001) genes expression decreased significantly in treatment groups compared to busulfan-induced azoospermia. Conclusion: According to our findings, edaravone can improve spermatogenesis in busulfan-induced azoospermia through free radical scavenging and autophagy modulation in testicular tissue.

N1-Methylnicotinamide: Is it Time to Consider it as a Dietary Supplement for Athletes?

Exercise is considered to be a "medicine" due to its modulatory roles in metabolic disorders, such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduces serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeogenesis and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1). It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the activity of NNMT in the adipose tissue and acts as an inhibitor of its activity.NNMT-MNAM axis is more activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption of MNAM during training, especially endurance training, could boost exercise capacity and improve performance. Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports medicine.

Potential Therapeutic Effects of Melatonin Mediate via miRNAs in Cancer.

miRNAs are evolutionarily conserved non-coding ribonucleic acids with a length of between 19 and 25 nucleotides. Because of their ability to regulate gene expression, miRNAs have an important function in the controlling of various biological processes, such as cell cycle, differentiation, proliferation, and apoptosis. Owing to the long-standing regulative potential of miRNAs in tumor-suppressive pathways, scholars have recently paid closer attention to the expression profile of miRNAs in various types of cancer. Melatonin, an indolic compound secreted from pineal gland and some peripheral tissues, has been considered as an effective anti-tumor hormone in a wide spectrum of cancers. Furthermore, it induces apoptosis, inhibits tumor metastasis and invasion, and also angiogenesis. A growing body of evidence indicates the effects of melatonin on miRNAs expression in broad spectrum of diseases, including cancer. Due to the long-term effects of the regulation of miRNAs expression, melatonin could be a promising therapeutic factor in the treatment of cancers via the regulation of miRNAs. Therefore, in this review, we will discuss the effects of melatonin on miRNAs expression in various types of cancers.