Melatonin enhances function of porcine immature Sertoli cells via modulating gene expression and metabolism
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PROVIDER: PRJNA1160260 | ENA |
REPOSITORIES: ENA
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Project description:Melatonin (MT), a neurohormone synthesized and secreted primarily by the pineal gland, is of vital function to animal reproduction. However, the effect of MT treatment on porcine immature Sertoli cells (iSCs) remains unclear. Here, MT treatment (10nM, 36h) could elevate mitochondrial function and reduce oxidative stress, therefore inhibit apoptosis of porcine iSCs. Transcriptome profiling identified 39 differentially expressed genes (DEGs) (33 known and 9 novel) (10nM MT vs. Control), mainly involved in GO terms of steroid metabolic process, glutamine metabolic process, oxidoreductase activity and G protein coupled receptor binding, and KEGG pathways of steroid biogenesis, pyruvate metabolism, NF-kappa B and AMPK signal pathways. RT-qPCR validated 6 DEGs (Phgdh, Scd, Hmgcs1, Cytb, Pck2 and Sqle) induced by MT to be with the similar change trend to RNA-seq results. The protein level of HMGCS1 and the estradiol level were confirmed to be significantly decreased by MT (10nM, 36h) treatment of porcine iSCs. Inhibition of HMGCS1 in porcine iSCs could significantly reduce the level of estradiol. The levels of cholesterol content within cells and lactate in culture medium were unchanged by MT (10nM, 36h). 14 metabolites were significantly altered by MT (10nM, 36h) treatment of porcine iSCs. Which were involved in multiple vital metabolic pathways. Collectively, MT treatment of porcine iSCs could promote functions of porcine iSCs via modulating gene expression and metabolism.
2025-08-26 | GSE277033 | GEO
Project description:Melatonin mitigates Chloroquine-induced defects in porcine immature Sertoli cells
| PRJNA750330 | ENA
Project description:Chloroquine (CQ) could function as a lysosomotropic inhibitor to impair the autophagy-lysosome pathway, and is widely used to treat malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear.;Here we showed that CQ treatment reduced iSCs viability in a dose-dependent manner. CQ treatment (20µM) of iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis. Melatonin (MT) (10nM) could partially rescue CQ-induced phenotypic defects. Transcriptome profiling (RNA-seq) identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20µM CQ vs. DMSO control group), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, MT addition identified only 467 (224 up- and 243 down-regulated) DEGs (CQ+MT vs. DMSO), enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction, respectively.Collectively, CQ treatment could impair porcine iSC viability by deranging apoptosis- and autophagy related signaling pathways, which could be partially rescued by MT supplementation.
2024-07-06 | GSE180995 | GEO
Project description:<p>Chloroquine (CQ) is widely used in the therapy against malarial, tumor and recently the COVID-19 pandemic, as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway. We previously reported that CQ (20 µM, 36 h) could reprogram transcriptome and impair multiple signaling pathways vital to porcine immature Sertoli cells (iSCs). However, whether CQ treatment could affect the metabolomic compositions of porcine iSCs remains unclear. Here, we showed that CQ (20 µM, 36 h) treatment of porcine iSCs induced significant changes of 63 metabolites (11 up and 52 down) by the metabolomics method, which were involved in different metabolic pathways. Caffeic acid and esculetin, the top two up-regulated metabolites, were validated by ELISA. Furthermore, esculetin treatment (53 nM, 36 h) significantly decreased the viability and proliferation, suppressed the mitochondrial function, whereas promoted the apoptosis of porcine iSCs, similar to those by CQ treatment (20 µM, 36 h). Collectively, our results showed that CQ treatment induces metabolic changes, and its effect on porcine iSCs could be partially mediated by esculetin.</p>
2024-07-08 | MTBLS9273 | MetaboLights
Project description:To compare the the genomic profile of MEFs, immature Sertoli, mature Sertoli cells, and MEFs (NWD) after infection of Nr5a1, Wt1 and Dmrt1 after 1 month of dox exposure. MEFs (NWD) were infected with Nr5a1, Wt1 and Dmrt1 and were exposed to dox for 1 month. MEFs, immature Sertoli and mature Sertoli cells were cultured for 3 days and collected
2012-12-20 | E-GEOD-39649 | biostudies-arrayexpress
Project description:To compare the the genomic profile of MEFs, immature Sertoli, mature Sertoli cells, and MEFs (NWD) after infection of Nr5a1, Wt1 and Dmrt1 after 1 month of dox exposure.
2012-12-20 | GSE39649 | GEO
Project description:Extensive transcriptome alteration in response to acute heat stress in porcine immature Sertoli cells
| PRJNA707408 | ENA
Project description:Ascorbic acid promotes the reproductive function of porcine immature Sertoli cells through transcriptome reprogramming
| PRJNA641633 | ENA
Project description:Background：Vitamin C (ascorbic acid, AA) can regulate antioxidation and play a pivotal role in many cellular processes. However, the function of AA in the reproduction of male animals remains less explored. Results: Here, by first supplementing exogenous AA to porcine immature Sertoli cells (iSCs), we showed that AA could promote the proliferation, suppress apoptosis, and decrease the global nucleic acid methylation (5mC and m6A) levels of iSCs. After we profiled mRNA and long non-coding RNA (lncRNA) expression by transcriptome sequencing on iSCs (treated by 250μM AA for 36h), 1232 mRNAs and 937 lncRNAs were identified to be differentially expressed (DE). Gene enrichment analysis found these DE mRNA and lncRNAs to be significantly enriched in multiple biological pathways, including oxidoreductase activity, cell proliferation and apoptosis, regulation of hormone level, regulation of catalytic activity, developmental process, ATP metabolic and reproductive process. Specifically, for the reproductive process, 49 up- and 36 down-regulated DE mRNAs (including highly expressed genes, such as Tfcp2l1, Hmgcs1, Mmp7, Fndc3a, and Zfp36l1) are involved. Moreover, AA supplementation could promote the secretion of anti-müllerian hormone, inhibin B and lactate, and enhance the activity of lactate dehydrogenase as well. Conclusions: Taken together, AA could promote the reproductive function of pig iSCs, potentially through reprogramming the global transcriptome, and elevating hormone secretion and metabolite production.
2020-10-06 | GSE153157 | GEO
Project description:Vitamin C (Ascorbic acid, AA), as vital micro-nutrient, plays an essential role for male animal reproduction. Previously, we showed that vitamin C reprogrammed the transcriptome and proteome to change phenotypes of porcine immature Sertoli cells (iSCs). Here, we used LC-MS-based non-targeted metabolomics to further investigate the metabolic effects of vitamin C on porcine iSCs. The results identified 43 significantly differential metabolites (16 up and 27 down) as induced by vitamin C (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) treatment of porcine iSCs, which were mainly enriched in steroid related and protein related metabolic pathways. ELISA (Enzyme-Linked ImmunoSorbent Assay) showed that significantly differential metabolites of Dehydroepiandrosterone (DHEA) (involved in steroid hormone biosynthesis) and Desmosterol (involved in steroid degradation) were significantly increased, which were partially consistent with metabolomic results. Further integrative analysis of metabolomics, transcriptomics and proteomics data identified the strong correlation between the key differential metabolite of Dehydroepiandrosterone and 6 differentially expressed genes (DEGs)/proteins (DEPs) (HMGCS1, P4HA1, STON2, LOXL2, EMILIN2 and CCN3). Further experiments validated that HMGCS1 could positively regulate Dehydroepiandrosterone level. These data indicate that vitamin C could modulate the metabolism profile, and HMGCS1-DHEA could be the pathway to mediate effects exerted by vitamin C on porcine iSCs.
2024-07-31 | MTBLS9673 | MetaboLights