L-Carnitine and Male Fertility: Is Supplementation Beneficial?

L-Carnitine, a natural antioxidant found in mammals, plays a crucial role in the transport of long-chain fatty acids across the inner mitochondrial membrane. It is used as a nutritional supplement by professional athletes, improving performance and post-exercise recovery. Additionally, its therapeutic applications, including those in male infertility, have been investigated, as it may act as a defense mechanism against the excessive production of reactive oxygen species (ROS) in the testis, a process that can lead to sperm damage. This effect is achieved by enhancing the expression and activity of enzymes with antioxidant properties. Nevertheless, the mechanisms underlying the benefits of L-Carnitine remain unknown. This review aims to consolidate the current knowledge about the potential benefits of L-Carnitine and its role in male (in)fertility. Considering in vitro studies with Sertoli cells, pre-clinical studies, and investigations involving infertile men, a comprehensive understanding of the effects of L-Carnitine has been established. In vitro studies suggest that L-Carnitine has a direct influence on somatic Sertoli cells, improving the development of germ cells. Overall, evidence supports that L-Carnitine can positively impact male fertility, even at a relatively low dose of 2 g/day. This supplementation enhances sperm parameters, regulates hormone levels, reduces ROS levels, and subsequently improves fertility rates. However, further research is needed to elucidate the underlying mechanisms and establish optimal doses. In conclusion, the role of L-Carnitine in the field of male reproductive health is highlighted, with the potential to improve sperm quality and fertility.

A Comprehensive Review of the Impact of Chromium Picolinate on Testicular Steroidogenesis and Antioxidant Balance.

Low testosterone (T) levels are a major cause of male infertility, as this hormone is crucial for several processes throughout the entire male reproductive tract. Leydig cells (LC) produce T through testicular steroidogenesis. Disrupted LC function can hinder steroid production and fertility. Among the factors that affect steroidogenesis, endocrine-disrupting chemicals (EDCs) raise concerns, as they disturb hormonal signaling. Chromium is classified as an EDC, and its main forms are hexavalent (Cr(VI)) and trivalent chromium (Cr(III)). While Cr(III) is controversially regarded as an essential metal, its compound Cr(III) picolinate (CrPic3) is used as a nutritional supplement due to its antidiabetic and antioxidant properties. This review aims to identify the possible effects of CrPic3 on testicular steroidogenesis and thus, on male fertility. The detriments caused by CrPic3 in LC include the inhibition of enzymes involved in steroidogenesis, and, as in other cells, the induction of mutagenesis and apoptosis. Remarkably, CrPic3 impacts male fertility through the alteration of reactive oxygen species (ROS), T levels, and sperm parameters (sperm motility and abnormal sperm count). However, gaps and inconsistencies exist in the literature concerning its effects on male fertility. Thus, further research is imperative to comprehend the underlying mechanisms of CrPic3 in the physiological processes relevant to male fertility, ensuring the supplement's safety for use by men.

The role of ion homeostasis imbalance due to citrate accumulation in fluoroacetic acid (FAA) toxicity in Neurospora crassa.

Fluoroacetic acid (FAA) is a poison commonly used for the lethal control of invasive species in Australia and New Zealand. Despite its widespread use and long history as a pesticide, no effective treatment for accidental poisoning exists. Although it is known to inhibit the tricarboxylic acid (TCA) cycle, specific details of FAA toxicology have remained elusive, with hypocalcemia suggested to be involved in the neurological symptoms prior to death. Here, we study the effects of FAA on cell growth and mitochondrial function using the filamentous fungi Neurospora crassa as model organism. FAA toxicosis in N. crassa is characterized by an initial hyperpolarization and subsequent depolarization of the mitochondrial membranes, followed by a significant intracellular decrease in ATP and increase in Ca2+. The development of mycelium was markedly affected within 6 h, and growth impaired after 24 h of FAA exposure. Although the activity of mitochondrial complexes I, II and IV was impaired, the activity of citrate synthase was not affected. Supplementation with Ca2+ exacerbated the effects of FAA in cell growth and membrane potential. Our findings suggest that an imbalance created in the ratio of ions within the mitochondria may lead to conformational changes in ATP synthase dimers due to mitochondrial Ca2+ uptake, that ultimately result in the opening of the mitochondrial permeability transition pore (MPTP), a decrease in membrane potential, and cell death. Our findings suggest new approaches for the treatment research, as well as the possibility to use N. crassa as a high-throughput screening assay to evaluate a large number of FAA antidote candidates.

Impact of Chromium Picolinate on Leydig Cell Steroidogenesis and Antioxidant Balance Using an In Vitro Insulin Resistance Model.

Leydig cells (LCs) play a pivotal role in male fertility, producing testosterone. Chromium (III) picolinate (CrPic3), a contentious supplement with antidiabetic and antioxidant properties, raises concerns regarding male fertility. Using a rodent LC line, we investigated the cytotoxicity of increasing CrPic3 doses. An insulin resistance (IR) model was established using palmitate (PA), and LCs were further exposed to CrPic3 to assess its antioxidant/antidiabetic activities. An exometabolome analysis was performed using 1H-NMR. Mitochondrial function and oxidative stress were evaluated via immunoblot. Steroidogenesis was assessed by quantifying androstenedione through ELISA. Our results uncover the toxic effects of CrPic3 on LCs even at low doses under IR conditions. Furthermore, even under these IR conditions, CrPic3 fails to enhance glucose consumption but restores the expression of mitochondrial complexes CII and CIII, alleviating oxidative stress in LCs. While baseline androgen production remained unaffected, CrPic3 promoted androstenedione production in LCs in the presence of PA, suggesting that it promotes cholesterol conversion into androgenic intermediates in this context. This study highlights the need for caution with CrPic3 even at lower doses. It provides valuable insights into the intricate factors influencing LCs metabolism and antioxidant defenses, shedding light on potential benefits and risks of CrPic3, particularly in IR conditions.

Roles of Oxidative Stress in the Male Reproductive System: Potential of Antioxidant Supplementation for Infertility Treatment.

The decline of fertility in modern society is a serious worldwide concern, and the reasons behind it are complex and difficult to unveil. The fact that a big percentage of infertility cases remain diagnosed as idiopathic, turn the strategies to treat such conditions very limited. Nevertheless, one must agree that keeping the oxidative balance of the reproductive tissues should be one of the first lines of treatment for infertile patients. As reported, 30-80% of male infertile individuals present high levels of prooxidant species in the seminal fluid. Thus, antioxidant therapies, which consist of dietary supplementation therapy with one or more antioxidant compound, remain the first step in the treatment of male infertility. Nevertheless, the efficacy of such therapies is variable between individuals. The most common prescribed antioxidants are carnitines and vitamins C and E, but recently phytochemical quercetin has emerged as a potential compound for the treatment of oxidative stress in the male reproductive system. Although there are several animals' evidence about the great potential of quercetin for the treatment of infertility, clinical trials on this subject remain scarce.

Hyperoside Supplementation in Preservation Media Surpasses Vitamin C Protection Against Oxidative Stress-Induced Damages in Human Spermatozoa.

BACKGROUND/AIMS: Oxidative Stress (OS) is reported as one of the main causes of male infertility. Infertile couples often resort to assisted reproductive technology (ART) to achieve parenthood. However, preparation for ART protocols increases the exposer of gametes to OS. Thus, it is crucial to find suitable preservation media that can counteract the OS-induced damages in spermatozoa. In this work, we tested and compared the efficiency of vitamin C (VC) and hyperoside (HYP) as potential antioxidant supplements for sperm preservation media. METHODS: We evaluated the cytotoxicity of HYP (0, 5, 50, 100, and 500 µM) in spermatozoa. After incubation of sperm cells with VC (600 µM) and HYP (100 and 500 µM), in the presence and absence of H2O2 (300 µM), the following parameters were assessed: total sperm motility and vitality, OS biomarkers expression, total antioxidant capacity (TAC) of the media, percentage of DNA fragmentation, mitochondrial membrane potential (MMP), and metabolite quantification of the media by proton nuclear magnetic resonance (1H-NMR). RESULTS: The supplementation with VC (600 µM) and HYP (100 and 500 µM) did not induce any deleterious effects to the physiology and metabolism of the spermatozoa, after 1-hour of treatment. In the presence of H2O2 (300 µM), both VC and HYP were able to prevent some of the deleterious effects of H2O2 in sperm, which were represented by an increase in sperm motility, a decrease in DNA fragmentation, and a decreasing trend in lipid peroxidation levels. However, these antioxidants were not able to prevent the decrease of MMP associated with H2O2 treatment, nor were able to prevent the conversion of pyruvate into acetate (a reaction promoted by H2O2). CONCLUSION: The supplementation of sperm preservation media with VC and HYP could be beneficial for the preservation of sperm physiology. From the antioxidant conditions tested, the supplementation of media with HYP (100 µM) demonstrated the best results regarding sperm preservation, evidencing the higher antioxidant capacity of HYP compared to VC. Nevertheless, none of the antioxidants used was able to prevent the metabolic alterations promoted by H2O2 in spermatozoa.

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

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.

White Tea Intake Abrogates Markers of Streptozotocin-Induced Prediabetes Oxidative Stress in Rat Lungs'.

Prediabetes (PrDM) is a prodromal stage of diabetes mellitus (DM) with an increasing prevalence worldwide. During DM progression, individuals gradually develop complications in various organs. However, lungs are suggested to be affected later than other organs, such as the eyes, heart or brain. In this work, we studied the effects of PrDM on male Wistar rats' lungs and whether the regular consumption of white tea (WTEA) for 2 months contributes to the improvement of the antioxidant profile of this tissue, namely through improved activity of the first line defense antioxidant enzymes, the total antioxidant capacity and the damages caused in proteins, lipids and histone H2A. Our data shows that PrDM induced a decrease in lung superoxide dismutase and glutathione peroxidase activities and histone H2A levels and an increase in protein nitration and lipid peroxidation. Remarkably, the regular WTEA intake improved lung antioxidant enzymes activity and total antioxidant capacity and re-established the values of protein nitration, lipid peroxidation and histone H2A. Overall, this is the first time that lung is reported as a major target for PrDM. Moreover, it is also the first report showing that WTEA possesses relevant chemical properties against PrDM-induced lung dysfunction.

A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility.

PURPOSE: The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility. MATERIALS AND METHODS: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. RESULTS: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3-6 months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician's age, geographic origin, experience or training in male infertility. CONCLUSIONS: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide understanding of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer's Disease.

The lack of effective disease-modifying therapeutics to tackle Alzheimer's disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-ß (Aß) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

White tea intake prevents prediabetes-induced metabolic dysfunctions in testis and epididymis preserving sperm quality.

Prediabetes has been associated with alterations in male reproductive tract, especially in testis and epididymis. Moreover, in vitro studies described a promising action of tea (Camellia sinensis L.) against metabolic dysfunctions. Herein, we hypothesized that white tea (WTEA) ingestion by prediabetic animals could ameliorate the metabolic alterations induced by the disease in testicular and epididymal tissues, preserving sperm quality. WTEA infusion was prepared and its phytochemical profile was evaluated by 1H-NMR. A streptozotocin-induced prediabetic rat model was developed and three experimental groups were defined: control, prediabetic (PreDM) and prediabetic drinking WTEA (PreDM+WTEA). Metabolic profiles of testis and epididymis were evaluated by determining the metabolites content (1H-NMR), protein levels (western blot) and enzymatic activities of key metabolic intervenient. The quality of spermatozoa from cauda epididymis was also assessed. Prediabetes increased glucose transporter 3 protein levels and decreased lactate dehydrogenase activity in testis, resulting in a lower lactate content. WTEA ingestion led to a metabolic adaptation to restore testicular lactate content. Concerning epididymis, prediabetes decreased the protein levels of several metabolic intervenient, resulting in decreased lactate and alanine content. WTEA consumption restored most of the evidenced alterations, however, not lactate content. WTEA also improved epididymal sperm motility and restored sperm viability. Prediabetes strongly affected testicular and epididymal metabolic status and most of these alterations were restored by WTEA consumption, resulting in the improvement of sperm quality. Our results suggest that WTEA consumption can be a cost-effective strategy to improve prediabetes-induced reproductive dysfunction.

Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders.

BACKGROUND: Human metabolism is an essential biological process that involves the consumption of different substrates to ensure the nutritional and energetic needs of cells. The disruption of this highly regulated system constitutes the onset of several disorders/dysfunctions such as diabetes mellitus, cardiovascular diseases and hypertension. OBJECTIVE: In this review, we propose to discuss promising natural products that can act as modulators of cell metabolism and point towards possible targets to take into account in the development of new therapies against metabolic diseases. METHODS: After having defined our main focus, we undertook an intensive search of bibliographic databases to select the peer-reviewed papers that fits within the review thematic. The information of the screened papers was described in an organized manner through the review and different types of studies were included. RESULTS: Two hundred and seventy papers were included in the review, as well as one reliable website from the World Health Organization. Several articles described that pharmacological agents are commonly used to counteract metabolic disorders. However, in many cases these products are insufficient, represent high costs to health care systems and are associated with several undesirable effects, highlighting the need to search for new therapies. Notably, many papers reported the promising results of natural products in the treatment of several metabolic disorders, constituting a possible alternative or complementary strategy to pharmacological agents. CONCLUSION: The findings of this review confirm that the currently available treatments for metabolic disorders and its associated complications remain far below the expected results.

The single and synergistic effects of the major tea components caffeine, epigallocatechin-3-gallate and L-theanine on rat sperm viability.

Caffeine, epigallocatechin-3-gallate (EGCG) and L-theanine are the major components of tea (Camellia sinensis L.) and the main representatives of the classes of methylxanthines, catechins and free amino acids present in this beverage. There are many studies reporting tea's health benefits, however it is not clear if those effects are mediated by a single component or a synergistic action. This study aimed to evaluate the individual and synergistic effects of tea's major components on rat epididymal spermatozoa survival and oxidative profile during 3-day storage at room temperature (RT). For that, spermatozoa were incubated with caffeine (71 µg mL(-1)), EGCG (82 µg mL(-1)), or L-theanine (19 µg mL(-1)), alone or in combination. Spermatozoa viability was assessed by the eosin-nigrosin staining technique. The oxidative profile was established by evaluating the levels of carbonyl groups, protein nitration and lipid peroxidation. Supplementation of sperm storage medium with the three compounds together improved sperm viability, after 24, 48 and 72 h of incubation, relative to the control and the groups incubated with each component individually. However, at the end of the 72 h of incubation, there was an increase in protein oxidation in the group exposed to the three compounds, illustrating that the combined treatment triggers different alterations in sperm proteins during their maturational process in the epididymis. This study highlights the importance of the synergism between tea components for the beneficial effects usually attributed to this beverage, particularly in sperm storage at RT.

White tea consumption restores sperm quality in prediabetic rats preventing testicular oxidative damage.

Prediabetes represents a major risk factor for the development of type 2 diabetes mellitus (T2DM). It encompasses some, but not all, T2DM diagnostic criteria. Prediabetes has been recently associated with altered testicular function and increased testicular oxidative stress (OS). Tea is widely consumed and its anti-hyperglycaemic/antioxidant properties are known. This study aimed to evaluate whether white tea (WTEA) consumption by prediabetic rats could prevent testicular OS, preserving sperm quality. For that purpose, WTEA (presenting a high catechin content) was given to 30-day-old streptozotocin-induced prediabetic rats for 2 months. Testicular antioxidant potential and OS were evaluated, as well as sperm parameters, by standard techniques. WTEA consumption improved glucose tolerance and insulin sensitivity in prediabetic rats. Testicular antioxidant potential was increased by WTEA consumption, restoring protein oxidation and lipid peroxidation, although glutathione content and redox state were not altered. WTEA consumption improved sperm concentration and sperm quality (motility, viability and abnormality) was restored. Overall, WTEA consumption improved reproductive health of male prediabetic rats. Based on the study results, WTEA consumption appears to be a natural, economical and effective strategy to counteract the deleterious effects of prediabetes on male reproductive health, but further studies will be needed before a definitive recommendation is made.

Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

Tea (Camellia sinensis (L.)): a putative anticancer agent in bladder carcinoma?

The leaves of Camellia sinensis (L.) are the source of tea, the second most consumed beverage worldwide. Tea contains several chemical compounds such as polyphenols (mainly catechins), caffeine, theophylline, L-theanine, among many others. Polyphenolic compounds are mainly responsible for its significant antioxidant properties and anticarcinogenic potential. Bladder cancer is one of the most common types of cancer, and its progression and onset are thought to be controlled by dietary and lifestyle factors. Epidemiological studies showed that the regular consumption of tea can be a preventive factor for this type of cancer, and several in vivo and in vitro studies reported that tea and its components may interfere in the cancer cells' signaling, preventing the bladder tumor progression. The mechanisms responsible for this protection include deregulation of cell cycle, induction of apoptosis while protecting the surrounding healthy bladder cells, inhibition of metastization processes, among others. Herein, we discuss the potential beneficial effects of tea and tea components in bladder cancer prevention and/or treatment, and how they can be helpful in finding new therapeutic strategies to treat this type of cancer.

Melatonin alters the glycolytic profile of Sertoli cells: implications for male fertility.

Melatonin co-operates with insulin in the regulation of glucose homeostasis. Within the testis, glucose metabolism in the somatic Sertoli cells (SCs) is pivotal for spermatogenesis. Since the effects of melatonin on male reproductive physiology remain largely unknown, we hypothesized that melatonin may affect spermatogenesis by modulating SC metabolism, interacting with insulin. To test our hypothesis, rat SCs were maintained in culture for 24 h in the presence of insulin, melatonin or both and metabolite production/consumption was determined by proton nuclear magnetic resonance ((1)H-NMR). Protein levels of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were determined by western blot. LDH activity was also assessed. SCs treated with melatonin showed an increase in glucose consumption via modulation of GLUT1 levels, but decreased LDH protein expression and activity, which resulted in lower lactate production. Moreover, SCs exposed to melatonin produced and accumulated less acetate than insulin-exposed cells. The combined treatment (insulin plus melatonin) increased acetate production by SCs, but intracellular acetate content remained lower than in insulin exposed cells. Finally, the intracellular redox state, as reflected by intracellular lactate/alanine ratio, was maintained at control levels in SCs by melatonin exposure (i.e. melatonin, alone or with insulin, increased the lactate/alanine ratio versus cells treated with insulin). Furthermore, SCs exposed to insulin plus melatonin produced more lactate and maintained the protein levels of some glycolysis-related enzymes and transporters at control levels. These findings illustrate that melatonin regulates SCs metabolism, and thus may affect spermatogenesis. Since lactate produced by SCs provides nutritional support and has an anti-apoptotic effect in developing germ cells, melatonin supplementation may be an effective therapy for diabetic male individuals facing subfertility/infertility.

White tea as a promising antioxidant medium additive for sperm storage at room temperature: a comparative study with green tea.

Storage of sperm under refrigeration reduces its viability, due to oxidative unbalance. Unfermented teas present high levels of catechin derivatives, known to reduce oxidative stress. This study investigated the effect of white tea (WTEA) on epididymal spermatozoa survival at room temperature (RT), using green tea (GTEA) for comparative purposes. The chemical profiles of WTEA and GTEA aqueous extracts were evaluated by (1)H NMR. (-)-Epigallocatechin-3-gallate was the most abundant catechin, being twice as abundant in WTEA extract. The antioxidant power of storage media was evaluated. Spermatozoa antioxidant potential, lipid peroxidation, and viability were assessed. The media antioxidant potential increased the most with WTEA supplementation, which was concomitant with the highest increase in sperm antioxidant potential and lipid peroxidation decrease. WTEA supplementation restored spermatozoa viability to values similar to those obtained at collection time. These findings provide evidence that WTEA extract is an excellent media additive for RT sperm storage, to facilitate transport and avoid the deleterious effects of refrigeration.