Exogenous Spermine Research Articles

Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia

Colorectal cancer (CRC) ranks as China’s second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

Exogenous Spermine Promotes Grain Filling in Spring Wheat by Enhancing the Accumulation and Remobilization of Stem Reserves Under Drought Stress Conditions

Exogenous Spermine Promotes Grain Filling in Spring Wheat by Enhancing the Accumulation and Remobilization of Stem Reserves Under Drought Stress Conditions

Physiological and metabolomic analyses reveal the mechanism by which exogenous spermine improves drought resistance in alfalfa leaves (Medicago sativa L.).

Alfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa. In this study, we root applied 0.1, 0.5, and 1 mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes. The results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid. In conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress.

ArPAOs from A. roxburghii showed essential roles in polyamine mediating water stress tolerance

Anoectochilus roxburghii is a precious Chinese herb with excellent pharmacological effects. When meet stress, plants produced polyamines (PAs) which are identified in active tissues and play crucial roles in stress responses. Nevertheless, the molecular mechanism of PAs responding to stress in A. roxburghii were largely unknown. Here, for the first time, three PAOs in A. roxburghii were identified from transcriptome data and functionally analyzed. Expression analysis was performed using fluorescence quantitative PCR and eventually, transgenic Arabidopsis thaliana were created to confirm the biological function of ArPAOs. It was found that the highest expression was in young flower buds and the expression levels of three ArPAO genes in various tissues were also different, which indicated their different catalytic preferences and functions. Under the treatment of exogenous spermine and spermidine, the expression of three ArPAOs fluctuated and the overall expression level increased. Overexpression (OE) of ArPAOs could enhance water stress tolerance through mediating polyamine catabolism. It might because the excessive expression of ArPAOs reduce the content of spermine and spermidine, creating a negative feedback regulation upstream and causes plants manufacturing PAs which reinforce water stress tolerance. Taken together, the study firstly reported the overexpression of ArPAOs enhance plant water stress tolerance and regulate the content of polyamines. This work will provide a vital theoretical foundation for uncovering the operation and regulatory mechanism of ArPAOs in promoting plant development and managing stress.

The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis.

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF-β1-induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF-β1-induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

High-performance liquid chromatography determination of polyamine contents in poultry based on precolumn benzoyl chloride derivatization

Polyamines are widely present in animal cells and perform important physiological and biochemical functions. Moderate intake of polyamines contributes to good health. Poultry is one of the common sources of polyamines in daily life. However, different tissues from poultry contain different amounts of polyamine. In this study, an efficient and accurate method for the determination of polyamines was developed by high-performance liquid chromatography (HPLC) with precolumn benzoyl chloride derivatization. The linearity of the polyamines was good between 10–400 nmol/mL, with the limit of detection (LOD, S/N = 3) and limits of quantification (LOQ, S/N = 10) were 0.37 and 1.23 nmol/mL. The recoveries of the method ranged from 94.73 % to 106.58 % with high accuracy (RSD < 7 %) and no significant matrix effects or interferences. The RSD of intra-day, inter-day and inter-batch repeatability in the range of 0.07–1.57 %, 0.08–1.03 % and 1.46–4.57 %. The method was successfully used to detect polyamines in poultry tissue, with putrescine, spermidine and spermine levels ranging from 3.24 to 29.85 mg/kg, 0.46 to 164.11 mg/kg and 63.39 to 489.57 mg/kg, respectively. Polyamine levels were higher in the spleen, thymus and bursa of fabricius and lower in the heart and muscle. Furthermore, the method was employed to study the effect of exogenous spermine on polyamine deposition in different tissues of geese. In summary, the method is suitable for the detection of polyamine in animal tissues.

Metabolomic and transcriptomic analysis of flavonoids biosynthesis mechanisms in mulberry fruit (Hongguo 2) under exogenous hormone treatments

The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.

Spermine induced endogenous signal ameliorates osmotic stress in Lens culinaris.

The present study evaluates the alleviation of polyethylene glycol (PEG) mediated osmotic stress by exogenous spermine (SP) application on seeds of Lens culinaris. Seeds were soaked overnight with SP (0.05M) and PEG (10%) separately. Third set was prepared by combinedtreatment with SP (0.05M) and PEG (10%). Further, various physiological parameters, defense enzymes, phenol, flavonoid, nitric oxide (NO), proline content, chromosomal abnormality studies etc. was conducted after 5days of incubation. PEG application significantly hampered the seed germination, root length, shoot length, relative water content and vigour index. Application of PEG induced electrolytic leakage in rootcells. PEG application also significantly reduced the activities of different defense parameters viz. peroxidase, polyphenol oxidase, phenylalanine ammonia lyase and β-1,3 glucanase, total phenol and flavonoid accumulation over control. Reactive oxygen species, lipid peroxidation, cell death was found significantly high in PEG treated sets. However, NO level has been significantly decreased by PEG treatment. Cytological studies showed reduced mitotic index and highest abnormalities under osmotic stress. Contrary to that, application of SP either alone or in combination with PEG showed improved responses of aforesaid defense parameters compared to control and solely PEG treated sets. Interestingly, cytological abnormalities were also reduced in SP treated roots. Overall, these results suggests that SP application on seeds reduced the PEG induced damage and intricately improved the defense mechanisms which might help to fight against oxidative stress.

Difluoromethylornithine rebalances aberrant polyamine ratios in Snyder–Robinson syndrome

Snyder–Robinson syndrome (SRS) results from mutations in spermine synthase (SMS), which converts the polyamine spermidine into spermine. Affecting primarily males, common manifestations of SRS include intellectual disability, osteoporosis, hypotonia, and seizures. Symptom management is the only treatment. Reduced SMS activity causes spermidine accumulation while spermine levels are reduced. The resulting exaggerated spermidine:spermine ratio is a biochemical hallmark of SRS that tends to correlate with symptom severity. Our studies aim to pharmacologically manipulate polyamine metabolism to correct this imbalance as a therapeutic strategy for SRS. Here we report the repurposing of 2‐difluoromethylornithine (DFMO), an FDA‐approved inhibitor of polyamine biosynthesis, in rebalancing spermidine:spermine ratios in SRS patient cells. Mechanistic in vitro studies demonstrate that, while reducing spermidine biosynthesis, DFMO also stimulates the conversion of spermidine into spermine in hypomorphic SMS cells and induces uptake of exogenous spermine, altogether reducing the aberrant ratios. In a Drosophila SRS model characterized by reduced lifespan, DFMO improves longevity. As nearly all SRS patient mutations are hypomorphic, these studies form a strong foundation for translational studies with significant therapeutic potential.

Barley HOMOCYSTEINE METHYLTRANSFERASE 2 confers drought tolerance by improving polyamine metabolism.

Drought stress poses a serious threat to crop production worldwide. Genes encoding homocysteine methyltransferase (HMT) have been identified in some plant species in response to abiotic stress, but its molecular mechanism in plant drought tolerance remains unclear. Here, transcriptional profiling, evolutionary bioinformatics, and population genetics were conducted to obtain insight into the involvement of HvHMT2 from Tibetan wild barley (Hordeum vulgare ssp. agriocrithon) in drought tolerance. We then performed genetic transformation coupled with physio-biochemical dissection and comparative multi-omics approaches to determine the function of this protein and the underlying mechanism of HvHMT2-mediated drought tolerance. HvHMT2 expression was strongly induced by drought stress in tolerant genotypes in a natural Tibetan wild barley population and contributed to drought tolerance through S-adenosylmethionine (SAM) metabolism. Overexpression of HvHMT2 promoted HMT synthesis and efficiency of the SAM cycle, leading to enhanced drought tolerance in barley through increased endogenous spermine and less oxidative damage and growth inhibition, thus improving water status and final yield. Disruption of HvHMT2 expression led to hypersensitivity under drought treatment. Application of exogenous spermine reduced accumulation of reactive oxygen species (ROS), which was increased by exogenous mitoguazone (inhibitor of spermine biosynthesis), consistent with the association of HvHMT2-mediated spermine metabolism and ROS scavenging in drought adaptation. Our findings reveal the positive role and key molecular mechanism of HvHMT2 in drought tolerance in plants, providing a valuable gene not only for breeding drought-tolerant barley cultivars but also for facilitating breeding schemes in other crops in a changing global climate.

Exogenous spermine alleviates the negative effects of combined salinity and paraquat in tomato plants by decreasing stress-induced oxidative damage.

Plants are frequently exposed to different combinations of soil constraints including salinity and different herbicides. These abiotic conditions negatively affect photosynthesis, growth and plant development resulting in limitations in agriculture production. To respond to these conditions, plants accumulate different metabolites that restore cellular homeostasis and are key for stress acclimation processes. In this work, we analyzed the role of exogenous spermine (Spm), a polyamine involved in plant tolerance to abiotic stress, in tomato responses to the combination of salinity (S) and the herbicide paraquat (PQ). Our findings showed that application of Spm reduced leaf damage and enhanced survival, growth, photosystem II function and photosynthetic rate of tomato plants subjected to the combination of S and PQ. In addition, we revealed that exogenous Spm reduced H2O2 and malondialdehyde (MDA) accumulation in plants subjected to S+PQ, suggesting that the role of exogenous Spm in alleviating the negative effects of this stress combination could be attributed to a decrease in stress-induced oxidative damage in tomato plants. Taken together, our results identify a key role for Spm in improving plant tolerance to combined stress.

Influence of a phyA Mutation on Polyamine Metabolism in Arabidopsis Depends on Light Spectral Conditions.

The aim of the study was to reveal the influence of phyA mutations on polyamine metabolism in Arabidopsis under different spectral compositions. Polyamine metabolism was also provoked with exogenous spermine. The polyamine metabolism-related gene expression of the wild type and phyA plants responded similarly under white and far-red light conditions but not at blue light. Blue light influences rather the synthesis side, while far red had more pronounced effects on the catabolism and back-conversion of the polyamines. The observed changes under elevated far-red light were less dependent on PhyA than the blue light responses. The polyamine contents were similar under all light conditions in the two genotypes without spermine application, suggesting that a stable polyamine pool is important for normal plant growth conditions even under different spectral conditions. However, after spermine treatment, the blue regime had more similar effects on synthesis/catabolism and back-conversion to the white light than the far-red light conditions. The additive effects of differences observed on the synthesis, back-conversion and catabolism side of metabolism may be responsible for the similar putrescine content pattern under all light conditions, even in the presence of an excess of spermine. Our results demonstrated that both light spectrum and phyA mutation influence polyamine metabolism.

Analysis of gene expression related to polyamine concentration and dimorphism induced in ornithine decarboxylase (odc) and spermidine synthase (spd) Ustilago maydis mutants

Polyamines are ubiquitous small organic cations, and their roles as regulators of several cellular processes are widely recognized. They are implicated in the key stages of the fungal life cycle. Ustilago maydis is a phytopathogenic fungus, the causal agent of common smut of maize and a model system to understand dimorphism and virulence. U. maydis grows in yeast form at pH 7 and it can develop its mycelial form in vitro at pH 3. Δodc mutants that are unable to synthesize polyamines, grow as yeast at pH 3 with a low putrescine concentration, and to complete its dimorphic transition high putrescine concentration is require. Δspd mutants require spermidine to grow and cannot form mycelium at pH 3. In this work, the increased expression of the mating genes, mfa1 and mfa2, on Δodc mutants, was related to high putrescine concentration. Global gene expression analysis comparisons of Δodc and Δspd U. maydis mutants indicated that 2,959 genes were differentially expressed in the presence of exogenous putrescine at pH 7 and 475 genes at pH 3. While, in Δspd mutant, the expression of 1,426 genes was affected by exogenous spermine concentration at pH 7 and 11 genes at pH 3. Additionally, we identified 28 transcriptional modules with correlated expression during seven tested conditions: mutant genotype, morphology (yeast, and mycelium), pH, and putrescine or spermidine concentration. Furthermore, significant differences in transcript levels were noted for genes in modules relating to pH and genotype genes involved in ribosome biogenesis, mitochondrial oxidative phosphorylation, N-glycan synthesis, and Glycosylphosphatidylinositol (GPI)-anchor. In summary, our results offer a valuable tool for the identification of potential factors involved in phenomena related to polyamines and dimorphism.

Effect of Exogenous Spermine on Biofilm Formation in Mycobacteria by Stimulating the Synthesis of Glycopeptidolipids

Biofilm formation is of great interest by its ability to increase bacterial tolerance to antibiotics that represent a serious problem for modern medicine. Among mycobacteria, which are also capable of forming biofilms, there are pathogens of socially dangerous infections, including tuberculosis. Basing on these data, the strains of Mycolicibacterium smegmatis mc2 155 were chosen as the objects of this study, including the parent strain without deletions and its mutants with one (ΔrelMsm) and double (ΔrelMsmΔrelZ) chromosomal deletions of the genes responsible for the synthesis of alarmone synthetase enzymes. Biofilms of mutant strains exhibited defects in biofilm formation. We have shown that the integrity, hydrophobicity, and the level of biomass of surface mycobacterial biofilms are dependent on the amount of glycopeptidolipids (GPL) in cells. The level of GPL depends on the activity of alarmone synthetases. The biogenic polyamine spermine is able to enhance the production of GPLs, restoring the integrity of biofilms of mutant strains. It is possible that this effect of spermine is caused by the influence on the activity of mycobacterial alarmone synthetases, which makes promising the further studying the molecular mechanisms of its action.

EXOGENOUS SPERMINE MEDIATED RESPONSES OF CATALASE AND PEROXIDASE UNDER SALT STRESS IN WHEAT (Triticum aestivum em Thell.)

Soil salinity is a major problem in many countries that adversely affects crop growth. Salinity-affected areas are not fit for crop cultivation and they only support a few halophytes. Several million ha of land were turned into saline soils due to human interference. Salinity stress is considered one of the major environmental stresses and mitigation of it is necessary for sustainable crop production. In the presentinvestigation four wheat cultivars differ in their tolerance to salinity viz. DBW 88, HD 3086, Kharchia 65and KRL 210 were chosen with an aim to study the effect of salinity stress and subsequent sperminetreatment on catalase and peroxidase enzymes which are responsible for the detoxification of reactive oxygenspecies (ROS). It is well documented that plant polyamine (PA), spermine is induced under stress conditionsand imparts tolerance against salinity stress. Effect of exogenous spermine treatment on catalase andperoxide activities were also studied. Catalase activity increased in all four varieties and more increase wasobserved in Kharchia 65 and lesser increase was observed in DBW88 at 21 days after sowing (DAS). Highestcatalase activity with spermine 0.5 mM concentration was observed and it was higher at 15 days aftertreatment (DAT). Mean catalase activity was found higher at 0 DAT in Kharchia 65 and KRL 210 and theactivity was highest at 5 DAT in DBW88 and HD 3086 at 90 DAS. Peroxidase activity increased withincreasing levels of salinity, but the activity was decreased with spermine treatment at 21 DAS. Highestperoxidase activity recorded in Kharchia 65 at 15 DAT and lowest was in DBW 88 at 5 DAT. Peroxidaseactivity decreased with spermine treatment in control and 8 dsm-1 and increased at 12 dsm-1 in all fourvarieties at 90 DAS.

Strategies for anti-oxidative stress and anti-acid stress in bioleaching of LiCoO2 using an acidophilic microbial consortium.

High metal ion concentrations and low pH cause severely inhibit the activity of an acidophilic microbial consortium (AMC) in bioleaching. This work investigated the effects of exogenous spermine on biofilm formation and the bioleaching efficiency of LiCoO2 by AMC in 9K medium. After the addition of 1mM spermine, the activities of glutathione peroxidase and catalase increased, while the amount of H2O2, intracellular reactive oxygen species (ROS) and malondialdehyde in AMC decreased. These results indicated that the ability of AMC biofilm to resist oxidative stress introduced by 3.5g/L Li+ and 30.1g/L Co2+ was improved by spermine. The activity of glutamate decarboxylase was promoted to restore the intracellular pH buffering ability of AMC. Electrochemical measurements showed that the oxidation rate of pyrite was increased by exogenous spermine. As a result, high bioleaching efficiencies of 97.1% for Li+ and 96.1% for Co2+ from a 5.0% (wv-1) lithium cobalt oxide powder slurry were achieved. This work demonstrated that Tafel polarization can be used to monitor the AMC biofilm's ability of uptaking electrons from pyrite during bioleaching. The corrosion current density increased with 1mM spermine, indicating enhanced electron uptake by the biofilm from pyrite.

Exogenous spermine inhibits high glucose/oxidized LDL-induced oxidative stress and macrophage pyroptosis by activating the Nrf2 pathway.

Evidence suggests that macrophage pyroptosis promotes the progression of diabetic atherosclerosis. Spermine, a natural cellular metabolite, demonstrates a protective effect against cardiovascular diseases. However, whether spermine has a protective effect against macrophage pyroptosis caused by high glucose (HG) and oxidized low-density lipoprotein (ox-LDL) conditions remains to be elucidated. To investigate the protective effect of spermine and the related underlying mechanism, THP-1 macrophages were treated with HG/ox-LDL, spermine, or the specific nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385. Cell viability was detected using CCK-8, cell membrane permeability was analyzed using lactate dehydrogenase (LDH) and Hoechst/propidium iodide staining and pyroptosis-related gene and protein expression levels were evaluated using polymerase chain reaction and western blot analysis. Spermine showed a potent preventive effect on THP-1 macrophage pyroptosis and oxidative stress induced by HG/ox-LDL. Cells treated with spermine showed increased cell viability, reduced reactive oxygen species (ROS) production, decreased LDH levels in the supernatant and reduced cell swelling. In addition, spermine significantly reduced NLR family pyrin domain containing 3, cleaved caspase-1, N-gasdermin D and IL-1β expression, as well as IL-1β levels in the supernatant. This demonstrated that the inhibition of pyroptosis and oxidative stress due to spermine was Nrf2 dependent. Furthermore, spermine enhanced Nrf2 nuclear translocation, thereby increasing heme oxygenase-1 and NADPH quinone oxidoreductase-1 expression, which subsequently reduced ROS production. In addition, the anti-pyroptotic and antioxidant effects of spermine were reversed by ML385 inhibition of Nrf2. It was concluded that spermine prevented macrophage pyroptosis and increased ROS overproduction by activating the Nrf2 pathway. The data suggested that spermine may be a potential novel drug for the treatment of diabetic atherosclerosis because it targets macrophage pyroptosis.

Exogenous spermine treatment modulates senescence and maintains postharvest quality of guava fruit

Exogenous spermine treatment modulates senescence and maintains postharvest quality of guava fruit

The effect of exogenous spermine application on some biochemichal and molecular properties in hordeum vulgare l. under both normal and drought stress

The effect of exogenous spermine application on some biochemichal and molecular properties in hordeum vulgare l. under both normal and drought stress

Polyamine metabolism links gut microbiota and testicular dysfunction

BackgroundMale fertility impaired by exogenous toxins is a serious worldwide issue threatening the health of the new-born and causing infertility. However, the metabolic connection between toxic exposures and testicular dysfunction remains unclear.ResultsIn the present study, the metabolic disorder of testicular dysfunction was investigated using triptolide-induced testicular injury in mice. We found that triptolide induced spermine deficiency resulting from disruption of polyamine biosynthesis and uptake in testis, and perturbation of the gut microbiota. Supplementation with exogenous spermine reversed triptolide-induced testicular dysfunction through increasing the expression of genes related to early and late spermatogenic events, as well as increasing the reduced number of offspring. Loss of gut microbiota by antibiotic treatment resulted in depletion of spermine levels in the intestine and potentiation of testicular injury. Testicular dysfunction in triptolide-treated mice was reversed by gut microbial transplantation from untreated mice and supplementation with polyamine-producing Parabacteroides distasonis. The protective effect of spermine during testicular injury was largely dependent on upregulation of heat shock protein 70s (HSP70s) both in vivo and in vitro.ConclusionsThe present study linked alterations in the gut microbiota to testicular dysfunction through disruption of polyamine metabolism. The diversity and dynamics of the gut microbiota may be considered as a therapeutic option to prevent male infertility.1i44qFJDRbDet-fJN3JiqxVideo