Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile

Dias, Tânia R.; Alves, Marco G.; Almeida, Susana; Silva, Joaquina; Barros, Alberto; Sousa, Mário; Silva, Branca M.; Silvestre, Samuel; Oliveira, Pedro F.

doi:10.1016/j.jsbmb.2015.06.004

Cited by 14 publications

(11 citation statements)

References 78 publications

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“…50 Moreover, both FSH and T promote the supportive role of SCs in this process by regulating SC physiology 6,11 and specifically metabolism 6 through stimulating glycolysis by increasing glucose uptake and/or modulating glycolysis-related enzymes. 6,51,52 Our results on the role of Glo1 in protecting cells from apoptosis through the control of MG-derived AGEs levels are in agreement with the existing literature in other cell models, 26e31,53e55 including oocytes. 36e38 More importantly, our findings extend our knowledge on Glo1's role in the male reproductive system, which has never been done before.…”

Section: Discussionsupporting

confidence: 91%

Testosterone and Follicle Stimulating Hormone–Dependent Glyoxalase 1 Up-Regulation Sustains the Viability of Porcine Sertoli Cells through the Control of Hydroimidazolone– and Argpyrimidine-Mediated NF-κB Pathway

Antognelli

Mancuso

Frosini

et al. 2018

The American Journal of Pathology

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Because Sertoli cells (SCs) play a central role in germ cell survival, their death may result in marked germ cell loss and infertility. SCs are the only somatic cells within the seminiferous tubules and are essential for regulating spermatogenesis. Factors that enhance or diminish the viability of SCs may have profound effects on spermatogenesis. Yet the mechanisms underlying the maintenance of SC viability remain largely unknown. Glyoxalase 1 (Glo1) detoxifies methylglyoxal (MG), a highly reactive carbonyl species mainly formed during glycolysis, which is a potent precursor of cytotoxic advanced glycation end products (AGEs). Hydroimidazolone (MG-H1) and argpyrimidine (ArgPyr) are AGEs resulting from MG-mediated post-translational modification of arginine residues in various proteins. The role of Glo1 and MG-derived AGEs in regulating the fate of SCs has never been investigated. By using gene silencing and the specific MG scavenger, aminoguanidine, the authors demonstrate that Glo1, under testosterone and follicle-stimulating hormone control, sustains viability of porcine neonatal SCs through a mechanism involving the NF-κB pathway. Glo1 knockdown induces a mitochondrial apoptotic pathway driven by the intracellular accumulation of MG-H1 and ArgPyr that desensitizes NF-κB signaling by modifying the inhibitor of NF-κB kinase, IKKß. This is the first report describing a role for Glo1 and MG-derived AGEs in SC biology, providing valuable new insights into the potential involvement of this metabolic axis into spermatogenesis.

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Section: Discussionsupporting

confidence: 91%

Testosterone and Follicle Stimulating Hormone–Dependent Glyoxalase 1 Up-Regulation Sustains the Viability of Porcine Sertoli Cells through the Control of Hydroimidazolone– and Argpyrimidine-Mediated NF-κB Pathway

Antognelli

Mancuso

Frosini

et al. 2018

The American Journal of Pathology

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“…We found that the DHEA-S concentration was lower in the CAP patients than in controls, and its levels were inversely correlated with disease severity. Dehydroepiandrosterone (DHEA) is the most abundant adrenal steroid hormone in humans, and DHEA-S, the sulphated ester of DHEA, is the hydrophilic storage form bound to albumin in the bloodstream [ 27 ]. It has been shown that DHEA modulates the function of the immune system [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity

Zheng

Luo

et al. 2018

Crit Care

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BackgroundThis study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment.MethodsA total of 175 individuals including 119 CAP patients and 56 controls were enrolled and divided into two cohorts. Serum samples from a discovery cohort (n = 102, including 38 non-severe CAP, 30 severe CAP, and 34 age and sex-matched controls) were determined by untargeted ultra-high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics. Selected differential metabolites between CAP patients versus controls, and between the severe CAP group versus non-severe CAP group, were confirmed by targeted mass spectrometry assays in a validation cohort (n = 73, including 32 non-severe CAP, 19 severe CAP and 22 controls). Pearson’s correlation analysis was performed to assess relationships between the identified metabolites and clinical severity of CAP. The area under the curve (AUC), sensitivity and specificity of the metabolites for predicting the severity of CAP were also investigated.ResultsThe metabolic signature was markedly different between CAP patients and controls. Fifteen metabolites were found to be significantly dysregulated in CAP patients, which were mainly mapped to the metabolic pathways of sphingolipid, arginine, pyruvate and inositol phosphate. The alternation trends of five metabolites among the three groups including sphinganine, p-Cresol sulfate, dehydroepiandrosterone sulfate (DHEA-S), lactate and l-arginine in the validation cohort were consistent with those in the discovery cohort. Significantly lower concentrations of sphinganine, p-Cresol sulfate and DHEA-S were observed in CAP patients than in controls (p < 0.05). Serum lactate and sphinganine levels were positively correlated with confusion, urea level, respiratory rate, blood pressure, and age > 65 years (CURB-65), pneumonia severity index (PSI) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, while DHEA-S inversely correlated with the three scoring systems. Combining lactate, sphinganine and DHEA-S as a metabolite panel for discriminating severe CAP from non-severe CAP exhibited a better AUC of 0.911 (95% confidence interval 0.825–0.998) than CURB-65, PSI and APACHE II scores.ConclusionsThis study demonstrates that serum metabolomics approaches based on the LC-MS/MS platform can be applied as a tool to reveal metabolic changes during CAP and establish a metabolite signature related to disease severity.Trial registrationClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2049-2) contains supplementary material, which is available to authorized users.

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“…Previous studies have evidenced significant metabolic similarities between hSCs and cancer cells (for review (Oliveira et al, 2015a)). Still, studies from our research group have reported that the intensive glycolytic activity of hSCs is not always correlated with the proliferative properties of these cells (Dias et al, 2015a;Jesus et al, 2015;Martins et al, 2015), as frequently happens with cancer cells (for review (Oliveira et al, 2015a)). The results here presented demonstrated a dose-dependent decrease of hSCs proliferation when exposed to 5 and 50 μM of EGCG, evidencing a clear anti-proliferative effect of this compound on these testicular cells.…”

Section: Mitochondrial Complexesmentioning

confidence: 98%

“…A sulforhodamine B (SRB) colorimetric assay was performed as previously described (Fricker, 1994), to evaluate hSCs proliferative responses to the culture media (Dias et al, 2015a). In brief, hSCs were plated in a 96-well culture plate (same amount of cells per well), left to grow until reaching a confluence of 60-70% and treated with the test culture media containing 0, 5 or 50 μM of EGCG for 24 h. Then, cells were fixed overnight (at − 20°C) with a mixture containing 1% acetic acid and 99% methanol and subsequently stained with 0.05% (w/v) SRB dissolved in 1% acetic acid for 1 h. Unbound SRB was removed by washing with 1% acetic acid, whereas the bound SRB was solubilized with 10 mM Tris base (pH 10) in a shaker for 10 min.…”

Section: Sulforhodamine B Assaymentioning

confidence: 99%

Implications of epigallocatechin-3-gallate in cultured human Sertoli cells glycolytic and oxidative profile

Dias

Alves

Silva

et al. 2017

Toxicology in Vitro

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Sertoli cells are crucial for the success of spermatogenesis, which is the biological process that ensures male fertility. These cells present high metabolic rates, being often subjected to high oxidative stress levels that, if uncontrolled, may compromise male fertility. Since the most abundant tea catechin, epigallocatechin-3-gallate (EGCG), has demonstrated a potent preventive activity against oxidative stress, we have evaluated its effect at concentrations of 5 and 50μM, on the metabolism, mitochondrial functionality and oxidative profile of human Sertoli cells (hSCs). While, the highest concentration of EGCG (50μM) increased glucose and pyruvate consumption, it decreased the conversion of pyruvate to alanine to sustain a regular lactate production. However, despite maintaining Krebs cycle functionality, EGCG (50μM) decreased mitochondrial membrane potential of hSCs, which could compromise the normal rates of ATP production. Interestingly, oxidative damages to proteins and lipids decreased in this experimental group, which may be valuable for the nutritional support of spermatogenesis.

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Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile

Cited by 14 publications

References 78 publications

Testosterone and Follicle Stimulating Hormone–Dependent Glyoxalase 1 Up-Regulation Sustains the Viability of Porcine Sertoli Cells through the Control of Hydroimidazolone– and Argpyrimidine-Mediated NF-κB Pathway

Testosterone and Follicle Stimulating Hormone–Dependent Glyoxalase 1 Up-Regulation Sustains the Viability of Porcine Sertoli Cells through the Control of Hydroimidazolone– and Argpyrimidine-Mediated NF-κB Pathway

Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity

Implications of epigallocatechin-3-gallate in cultured human Sertoli cells glycolytic and oxidative profile

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