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Background: Seminal oxidative stress has been shown to be a key factor in the development of male infertility. However, the benefits of infertility treatments with antioxidants such as coenzyme Q10 (CoQ10) remains controversial., Objectives: The aim of the present study was to assess the effects of CoQ10 supplementation on semen quality, i.e., semen volume, total sperm number, sperm concentration, total sperm motility, percentage of progressive sperm motility and sperm morphology. In addition, the effects of CoQ10 supplementation on circulating testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B levels were evaluated., Design: A systematic review and a meta-analysis of randomized controlled trials (RCTs) were performed to assess the effects of CoQ10 supplementation on semen quality and serum levels of male reproductive hormones., Methods: We conducted a strategic literature search in the Cochrane, EMBASE, PubMed/MEDLINE, Scopus, and Web of Science databases and collected only RCTs. The data in the collected RCTs were then meta-analyzed according to PRISMA guidelines., Results: Out of 2,144 collected studies, only eight were classified eligible. The studies included a total of 877 male subjects; 462 CoQ10-treated and 415 untreated/placebo-treated. We found significantly higher total sperm counts (SMD -13.38 [95% CI: -16.33, -10.43] P < 0.0001), total (SMD -7.26 [95% CI: -10.15, -4.36] P< 0.00001) and progressive motility (SMD -6.386 [95% CI: -10.04, -2.73] P= 0.0006), and normally formed sperm (SMD -1.96 [95% CI: -3.29, -0.62] P= 0.004) in CoQ10-treated male subjects compared with untreated/placebo-treated male subjects. Nonetheless, there was a significant inter-study heterogeneity in these studies. Moreover, significantly higher serum testosterone (SMD -0.59 [95% CI: -0.79, -0.40] P< 0.00001) and inhibin B levels (SMD -0.92 [95% CI: -1.47, -0.37] P= 0.001) were recorded in CoQ10-treated subjects compared to untreated/placebo-treated subjects. In addition, CoQ10 supplementation significantly lowered serum LH (SMD 1.77 [95% CI: 1.26, 2.28] P< 0.00001) and FSH concentrations (SMD 1.60 [95% CI: 1.38, 1.81] P< 0.00001). Interestingly, there was no significant inter-study heterogeneity in the hormonal studies. However, CoQ10 supplementation had no significant effect on semen volume (SMD 0.12 [95% CI: -0.13, 0.37] P = 0.34) and sperm concentration (SMD -6.69 [95% CI: -16.28, 2.90] P= 0.17)., Conclusion: Our study shows that CoQ10 supplementation increases total sperm count, total and progressive sperm motility, and the proportion of normally formed sperm in association with higher serum testosterone and inhibin B levels. Our study therefore supports the view in the literature of a beneficial use of CoQ10 in male infertility treatment. However, further well-designed RCTs with sufficiently large numbers of subjects are required to reach a final conclusion., Competing Interests: JH is the CEO of Acrolytics LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Akhigbe, Fidelis, Adekunle, Ashonibare, Akorede, Shuaibu, Hassan, Adegbola, Ashonibare, Oladapo, Adeogun, Bamidele, Oyedokun, Mukolokota, Kukoyi, Oladipo, Adelowo, Akangbe, Hughes, Ricken, Culty, Avellar and Akhigbe.)

Regular exercise is widely recognized for its numerous physical and mental benefits, but its effects on male reproductive health are less understood. This review aims to summarize the current evidence on the impact of exercise on male reproduction, including reproductive hormone regulation, spermatogenesis sperm quality, and fertility. Moderate exercise improves sperm quality, increasing count, motility, and morphology, while excessive and severe exercise may have detrimental effects. Exercise positively influences fertility by reducing oxidative stress and enhancing sperm DNA integrity. Regular physical activity regulates reproductive hormones, including testosterone, follicle-stimulating hormone, and luteinizing hormone. Exercise-induced weight management and improved insulin sensitivity also contribute to better reproductive health. In conclusion, exercise has a profound impact on male reproductive health, with moderate physical activity promoting improved hormonal balance, sperm quality, and fertility. However, severe/excessive exercise exerts negative effects. These findings imply that a balanced exercise routine, usually mild to moderate, combined with a healthy lifestyle is essential for optimal male reproductive health. However, once exercise is severe and prolonged, it could impair male reproductive health. Further research is needed to understand the mechanisms underlying the exercise-reproduction relationship fully., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Adelowo, Akindele, Adegbola, Oyedokun, Akhigbe and Akhigbe.)

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that ferroptosis, a non-apoptotic, iron-dependent cell death pathway, is also involved in the pathophysiology of CT organ toxicity. CT provokes organ ferroptosis via system Xc - /GPX-4/GSH/SLC7A11 axis depletion, ferritinophagy, iron overload, lipid peroxidation and upregulation of ferritin-related proteins. Cisplatin (CP) and doxorubicin (DOX) are common CT drugs indicated to induce ferroptosis in vitro and in vivo. Studies have explored natural preventive and therapeutic strategies using ginger rhizome and its major bioactive compounds, 6-gingerol (6G) and zingerone (ZG), to combat mechanisms of CT side effect toxicity. Ginger extract, 6G and ZG mitigate non-ferroptotic oxidative inflammation, apoptosis and mitochondrial dysfunction mechanisms of CT side effect toxicity, but their effects on CT-induced ferroptosis remain unclear. Systematic investigations are, therefore, needed to unfold the roles of ginger, 6G and ZG on ferroptosis involved in CT side effect toxicity, as they are potential natural agents for the prevention of CT toxicity. This review reveals the ferroptotic and non-ferroptotic toxicity mechanisms of CT and the protective mechanisms of ginger, 6G and ZG against CT-induced, ferroptotic and non-ferroptotic organ toxicities., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Declaration of generative AI and AI-assisted technologies: The authors declare that there was no use of AI technologies in any form during the preparation of this work., (© 2024. The Author(s).)

A global decline in male fertility has been reported, and climate change is considered a major cause of this. Climate change refers to long-term shifts in temperatures and weather patterns, and results from greenhouse gas emissions like carbon dioxide and methane that act as a blanket wrapped around the earth, trapping heat and elevating temperatures. Sad to say, the consequences of climatic variation are beyond the dramatic elevated temperature, they include cold stress, increased malnutrition, air pollution, cardiovascular diseases respiratory tract infections, cancer, sexually transmitted infections, mental stress, and heat waves. These negative effects of climate change impair male reproductive function through multiple pathways, like ROS-sensitive signaling, suppression of steroidogenic markers, and direct damage to testicular cells. The present study aimed to describe the impact of the consequences of climate change on male reproductive health with details of the various mechanisms involved. This will provide an in-depth understanding of the pathophysiological and molecular basis of the possible climatic variation-induced decline in male fertility, which will aid in the development of preventive measures to abate the negative effects of climate change on male reproductive function., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Adaptogens, comprising plants and mushrooms, modulate the immune system, energy balance, and various physiological processes, including reproduction. Despite their potential benefits, the impact of adaptogens on reproductive function remains understudied. This review examines the effects of common adaptogens on male and female reproductive functions, highlighting their regulation of neuro-endocrine-immune interactions crucial for reproduction. While existing literature reveals varying impacts on reproductive function, most adaptogens exhibit beneficial effects, modulating neuroimmunology and promoting gonadal steroidogenesis, spermatogenesis, and folliculogenesis through direct mechanisms or suppression of oxidative stress and inflammation. Further experimental research is necessary to elucidate the mechanisms of action of adaptogens, which would significantly advance the management of reproductive disorders and other diseases. Validating these findings in clinical trials is also essential., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The hypothalamic-pituitary-gonadal axis, which regulates steroidogenesis and germ cell formation, closely regulates the reproduction process. Nonetheless, other chemical mediators, such as kisspeptin, influence this axis. Kisspeptin is a hypothalamic neuropeptide that modulates the function of this axis and also plays a central role in energy balance. The present study reviews the impact and associated mechanisms of kisspeptin on male and female reproduction based on available evidence in the literature. Kisspeptin and its neurons exert anorexigenic activity, thus maintaining adequate energy balance for optimal reproductive function. Also, they stimulate the release of GnRH, resulting in the optimal performance of gonadal physiological processes viz. production of steroid sex hormones and germ cells. However, studies linking kisspeptin to reproduction are yet scanty. Hence, studies exploring the upstream and downstream signaling pathways activated by kisspeptin concerning reproduction in an attempt to better understand the associated mechanisms of the regulatory activities of kisspeptin on reproduction are recommended. In addition, potential factors that may modulate kisspeptin activities may be useful in the management of infertility and perhaps, in the development of contraceptives for those who do not intend to achieve conception., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arsenic is a ubiquitous metalloid and heavy metal that contributes to the global decline in human fertility. Humans are constantly exposed to arsenic through biotic and abiotic sources, especially ingestion of arsenic-contaminated food and water. Its exposure is associated with several adverse health challenges, including reproductive toxicity. In spite of its reported adverse effects, arsenic exposure remains a global challenge. Hence, this study provides a comprehensive review of the literature on the impact and mechanism of arsenic on male and female reproductive function. Additionally, a review of the potential therapeutic strategies is presented. Evidence from the literature reveals that arsenic upregulates reactive oxygen species (ROS) generation which mediates arsenic-induced suppression of the hypothalamic-pituitary-gonadal axis and inactivation of 3β-HSD and 17β-HSD activities, leading to reduced gonadal steroidogenesis. Through several oxidative stress-dependent signaling, arsenic induces the apoptosis of the germ cells, thus contributing to the development of infertility. At the moment, there is no specific treatment for arsenic-induced reproductive toxicity. However, increasing data form the scientific literature reveals the benefits of antioxidants in ameliorating arsenic-induced reproductive toxicity. These molecules suppress ROS generation and maintain optimal activities of the hypothalamic-pituitary-gonadal axis, leading to optimal steroidogenesis and gametogenesis as well as improved germ cells. Overall, this study revealed the impact and associated mechanism of arsenic-induced reproductive toxicity. It also provides evidence from the literature demonstrating potential therapeutic measures in managing arsenic-induced reproductive toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The introduction of highly active antiretroviral therapy (HAART) has revolutionized the treatment of HIV/AIDS worldwide. The HAART approach is the combination of two or more antiretroviral drugs of different classes and are responsible for patient's survival and declining death rates from HIV/AIDS and AIDS-related events. However, the severe and persistent reproductive side effect toxicity of HAART regimens is of great concern to patients within the reproductive age. Till date, the underlying pathophysiology of the HAART-induced reproductive toxicity remains unraveled. Nevertheless, preclinical studies show that oxidative stress and inflammation may be involved in HAART-induced sperm-endocrine deficit and reproductive aberrations. Studies are emerging demonstrating the efficacy of plant-based and non-plant products against the molecular alterations and testicular toxicity of HAART. The testicular mechanisms of mitigation by these products are associated with enhancement of testicular steroidogenesis, spermatogenesis, inhibition of oxidative stress and inflammation. This review presents the toxic effects of HAART on spermatogenesis, reproductive hormones and testis integrity. It also provides insights on the molecular mechanisms underlying the mitigation of HAART testicular toxicity by plant-based and non-plant agents. However, effect of repurposing clinical drugs to combat HAART toxicity is unknown, and more mechanistic studies are evidently needed. Altogether, plant-based and non-plant products are potential agents for prevention of rampant endocrine dysfunction and testicular toxicity of HAART., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Adenomyosis is a gynaecological lesion that impairs female fertility and contributes to reduced quality of life. There are several surgical and medical options for the management of this lesion; however, women who wish to conceive opt for medical therapies such as the levonorgestrel intrauterine device (LNG-IUS) and dienogest, which have various outcomes. To date, there is no consensus regarding which is more effective., Objectives: To compare the effectiveness of LNG-IUS and dienogest for the management of adenomyosis, and explore the risk of occurrence of known side effects for both treatments., Design: Systematic review and meta-analysis exploring the effectiveness of LNG-IUS and dienogest for the management of adenomyosis., Methods: A literature search was conducted using PICO guidelines and EMBASE, PubMed/MEDLINE, Scopus and Web of Science databases. Only clinical trials were collected and analysed., Results: Of the 792 studies that were initially identified, six were eligible for inclusion in this study. The studies included a total of 707 women; of these, 270 were treated with LNG-IUS, 354 were treated with dienogest, and 83 were controls. All the studies were from Asia (Bangladesh n = 1, China n = 2, India n = 1, Japan n = 1, South Korea n = 1). Dienogest was found to reduce pelvic pain significantly, evidenced by a lower visual analogue scale score, compared with LNG-IUS. Also, dienogest led to a significant reduction in uterine volume compared with LNG-IUS. However, subjects in the LNG-IUS group had significantly higher levels of haemoglobin than those in the dienogest group. Nonetheless, the occurrence of side effects such as weight gain, breast tenderness/distension, headache, insomnia/sleep disorder, depression/mood disorder, skin disorder/acne, and coital discomfort/reduced libido were comparable in both treatment groups., Conclusion: Dienogest may be more effective than LNG-IUS for the management of adenomyosis, as it shows a superior effect in the reduction of pelvic pain and uterine volume. As only six studies were included in the present meta-analysis due to the paucity of data in the literature, it is recommended that well-designed randomized controlled trials comparing the effectiveness of dienogest with LNG-IUS should be conducted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to investigate the effect of arsenic exposure on urinary levels of arsenic metabolites, semen parameters, and testosterone concentrations. A systematic comprehensive literature search was conducted up till 31st January 2024 using Embase, MEDLINE/Pubmed, and Scopus. This study adopted the Population Exposure Comparator Outcome and Study Design (PECOS) framework. Four studies with a total of 380 control subjects and 347 exposed men were included. Arsenic exposure significantly increased urinary levels of total arsenic (Mean Difference (MD) - 53.35 [95 % Confidence Interval (CI): - 100.14, - 6.55] P= 0.03), and reduced primary arsenic methylation index (PMI) (MD 0.22 [95 % CI: 0.14, 0.31] P< 0.00001), semen volume (MD 0.30 [95 % CI: 0.05, 0.54] P= 0.02) and total testosterone (MD 0.48 [95 % CI: 0.23, 0.73] P= 0.0002). In addition, arsenic exposure marginally reduced sperm concentration (MD 25.04 [95 % CI: - 45.42, 95.50] P= 0.49) and total sperm motility (MD 22.89 [95 % CI: - 14.15, 59.94] P= 0.23). The present meta-analysis demonstrates that arsenic exposure lowers semen quality and testosterone levels. Since the general human population is exposed to arsenic occupationally or domestically, adequate strategic measures should be put in place to limit arsenic exposure in an attempt to preserve semen quality. In addition, studies investigating interventions that may inhibit the bioaccumulation of arsenic in men who are exposed are recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lead exposure has been implicated in the aetiopathogenesis of male infertility via an oxidative stress-sensitive pathway. Conversely, acetate has been shown to confer cellular protection by improving the antioxidant defense mechanism. Yet, the effect of acetate on lead-induced testicular toxicity, viz., dysregulation of testicular steroidogenesis and spermatogenesis, has not been reported. The present study probed the influence of acetate on lead-induced dysregulation of testicular steroidogenesis and spermatogenesis. In our study, a reduction in body weight gain and testicular weight was identified in lead-exposed rats. While histopathological results established distortion of testicular histoarchitecture, reduced germ cell count, and suppressed spermatogenesis, biochemical studies confirmed that lead-deregulated testicular steroidogenesis was associated with reduced circulating gonadotropin-releasing hormone and gonadotropins, as well as down-regulated testicular 3β-HSD and 17β-HSD activities. These findings were accompanied by increased testicular malondialdehyde, TNF-α, IL-1β, and IL-6, and reduced glutathione, thiol and non-thiol protein levels, total antioxidant capacity, superoxide dismutase, and catalase activities. In addition, lead exposure increased NF k B and Bax levels, as well as caspase 3 activity, but reduced Bcl-2 levels. However, co-administration of acetate ameliorated lead-induced alterations. Collectively, acetate attenuated lead-induced dysregulation of testicular steroidogenesis and spermatogenesis by targeting oxidative stress, NF k B-mediated inflammation, and caspase 3-driven apoptosis., Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00250-3., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. Materials and methods: The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). Results: Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. Conclusion: Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended., Competing Interests: Author JH is the Head of Acrolytics LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Akhigbe, Oyedokun, Akhigbe, Adenike, Oladipo and Hughes.)

Purpose: HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction., Materials and Methods: Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks., Results: Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation., Conclusion: In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.

Male reproductive functions, which include testicular steroidogenesis, spermatogenesis, and sexual/erectile functions are key in male fertility, but may be adversely altered by several factors, including hypoxia. This review demonstrates the impact of hypoxia on male reproductive functions. Acute exposure to hypoxia promotes testosterone production via stimulation of autophagy and upregulation of steroidogenic enzymes and voltage-gated L-type calcium channel, nonetheless, chronic exposure to hypoxia impairs steroidogenesis via suppression of the hypothalamic-pituitary-testicular axis. Also, hypoxia distorts spermatogenesis and reduces sperm count, motility, and normal forms via upregulation of VEGF and oxidative stress-sensitive signaling. Furthermore, hypoxia induces sexual and erectile dysfunction via a testosterone-dependent downregulation of NO/cGMP signaling and upregulation of PGE1/TGFβ1-driven penile endothelial dysfunction. Notably, hypoxia programs male sexual function and spermatogenesis/sperm quality via feminization and demasculinization of males and oxidative stress-mediated alteration in sperm DNA methylation. Since oxidative stress plays a central role in hypoxia-induced male reproductive dysfunction, studies exploring the effects of antioxidants and upregulation of transcription of antioxidants on hypoxia-induced male reproductive dysfunction are recommended., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The global prevalence of illicit drug use is on the increase with attendant complications like cardiorenal collapse. One such substance of abuse is rohypnol. Despite its ban in most countries, it remains a popular substance of abuse. Whether or not rohypnol induces cardiorenal injury and the associated mechanism is yet to be elucidated. Therefore, the present study investigated the effect of rohypnol on cardiorenal integrity and functions, and glucolipid metabolism. Forty-eight male Wistar rats randomized into six groups (n = 8/group) received (per os) vehicle, low-dose (2 mg/kg) and high-dose (4 mg/kg) rohypnol once daily for twenty eight days, with or without a cessation period. Data revealed that rohypnol exposure irreversibly caused insulin resistance, hyperglycaemia, and dyslipidaemia. This was accompanied by reduced cardiorenal mass and impaired cardiorenal cytoarchitecture and function. Furthermore, rohypnol treatment promoted oxidative stress, inflammation, genotoxicity, and decreased cardiorenal activities of Na + -K + -ATPase, Ca 2+ -ATPase, and Mg 2+ -ATPase. These alterations were associated with enhanced uric acid generation and caspase 3 activity in the cardiorenal complex. Thus, this study reveals that rohypnol exposure triggers cardiorenal toxicity with incident insulin resistance, glucolipid and cardiorenal proton pump dysregulation, altered redox state, and inflammation via enhancement of uric acid generation and caspase 3-dependent mechanism., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1β, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)