Melatonin protects against defects induced by malathion during porcine oocyte maturation
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE132618 | GEO | 2019/06/13
REPOSITORIES: GEO
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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:Melatonin protects against defects induced by malathion during porcine oocyte maturation
| PRJNA548540 | ENA
Project description:SIRT6, the sixth member of sirtuin family proteins, has been identified as a crucial regulator in multiple molecular pathways related to aging, including genome stability, DNA damage repair, telomere maintenance and inflammation. However, the exact roles of SIRT6 during mammalian oocyte meiosis have not yet fully clarified. Here, we investigated the critical events during porcine oocyte meiotic maturation with the treatment of SIRT6 specific inhibitor SIRT6-IN-1. We found that SIRT6 inhibition resulted in oocyte meiotic failure by displaying the poor expansion of cumulus cells and reduced rate of polar body extrusion. Meanwhile, the compromised spindle assembly, chromosome alignment and actin dynamics were also observed in SIRT6-inhibited oocytes. Moreover, inhibition of SIRT6 led to the defective cytoplasmic maturation by showing the abnormal distribution of cortical granules and their component ovastacin. Notably, we identified that expression of genes related to oocyte meiosis, oxidative phosphorylation and cellular senescence was remarkably altered in SIRT6-inhibited oocytes by transcriptome analysis, and validated that the meiotic defects caused by SIRT6 inhibition resulted from the excessive ROS-induced early apoptosis in oocytes. Taken together, our findings demonstrate that SIRT6 promotes the porcine oocyte meiotic maturation via maintaining the organelle dynamics.
2021-03-16 | GSE161068 | GEO
Project description:Spermidine is involved in a variety of biological processes, including DNA metabolism, autophagy and aging. Previous studies have shown that spermidine can increase the percentage of mouse oocytes developing into blastocysts after in vitro fertilization. However, none of the past studies elucidated the effects of spermidine supplementation on porcine oocyte maturation. Here, we choose appropriate dose of spermidine to be added to the maturation medium during in vitro maturation (IVM) to verify whether spermidine can actively promote the maturation of porcine oocytes. Our study provided substantial evidence that spermidine exposure promoted the porcine oocyte meiotic maturation. In addition, single-cell transcriptome analysis identified the target effectors of spermidine actions in porcine oocytes, further demonstrating that spermidine exposure enhanced mitochondrial distribution and function, leading to a reduced excessive oxidative stress-induced DNA damage and early apoptosis of porcine oocytes. These findings demonstrate that spermidine not only delays ageing and cancer treatment, but also improves the quality of germ cells, which may be less likely to suffer from sterility or infertility in humans and animals.
2024-11-30 | GSE217447 | GEO
Project description:Melatonin mitigates Chloroquine-induced defects in porcine immature Sertoli cells
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Project description:We report the application of single cell transcriptome sequencing technology for high-throughput profiling of the brilliant cresyl blue test-positive porcine oocytes had higher rates of meiotic maturation, lower death rates, and better cleavage and blastocyst rates as well. Single oocyte transcriptome sequencing on porcine germinal vesicle (GV) stage oocytes that differentially stained by BCB identified 155 genes with significant abundance differences, including CDC5L, LDHA, SPATA22, RGS2, PAIP1, WEE1B and HSP27, which enriched in functionally important signaling pathways, such as spliceosome, cell cycle, oocyte meiosis, and nucleotide excision repair.
2019-01-17 | GSE101181 | GEO
Project description:The proper mammalian oocytes maturation is recognized as reaching MII stage and accumulation of mRNA and proteins in cell cytoplasm following fertilization. The proper course of folliculogenesis and oogenesis is orchestrated with morphogenesis significantly influencing further zygote formation and embryos growth. This study was aimed to determinate new transcriptomic markers of porcine oocytes morphogenesis associated with cell maturation capacity. We used microarrays to detail the global programme of gene expression underlying changes before and after in vitro maturation of oocytes in sus scrofa
2017-03-31 | GSE97246 | GEO
Project description:In this study, we used tandem mass tag (TMT)-based quantitative approach to acquire proteomic profiles of porcine GV and MII oocytes and MII oocytes vitrified at the GV stage.
2021-07-01 | PXD023107 | Pride
Project description:The mechanisms of oocyte meiotic defects and low competence during ovarian aging remains elusive for decades. Using Hi-C (genome-wide chromatin conformation capture) and Smart RNA-seq of oocytes from 6- weeks or 10- months aged ovaries, the abnormal loose chromatin structures and disturbing expression of meiosis associated genes at metaphase I phase were disclosed. Furthermore, the transcriptomic landscape of granulosa cells (GCs) surrounding oocytes from young and aged ovaries reveled that oocyte meiotic maturation was accompanied with a robust increased expression of genes involved with the mevalonate (MVA) pathway in GCs from young ovaries but these genes expression was not upregulated to counterpart level in GCs from aged ovaries.The inhibitor of MVA pathway of GCs, Statins significantly decreased polar body extrusion rate and increased the rate of irregularly assembled spindles and misaligned chromosomes remarkably in oocytes of culumus-oocyte complex (COCs) from young ovaries . Correspondingly, the activitor of MVA pathway of GCs, Geranylgeraniol ameliorated ovarian reserve and reduced meiotic defects in oocytes of COCs from aged ovaries. Mechanistically, MVA pathway activation in GCs culminated oocyte meiotic maturation by upregulating EGF signaling via LH receptor on GCs surrounding oocytes. Together, MVA pathway is a promising therapeutic target for prompting quality of oocytes from aged ovaries.
2023-02-26 | GSE175835 | GEO
Project description:STUDY QUESTION: Does maternal age affect the maturated oocyte quality and the fol-lowing development after fertilization in human? SUMMARY ANSWER: Maternal age affects the quality of maturated oocytes by altering the stored mRNA levels in human, such as TOP2B. WHAT IS KNOWN ALREADY: Intracellular mRNAs in maturated oocytes are tran-scripted from the maternal genome during oogenesis and important for the zygotic genome activation (ZGA) after fertilization. Microarray data showed that maternal age affected polyadenylated transcript abundance in human oocytes. These genes are involved in in signaling pathway related to cell cycle regulation, chromosome alignment. However, which genes are the key genes affected by maternal age and important for the development after fertilization had not been reported. Therefore, single-cell RNA sequencing (scRNA-Seq) technology is employed in this study to screen the key genes affected by maternal age in human maturated oocytes. STUDY DESIGN, SIZE, DURATION: We isolated mRNA from maturated (MII) oo-cytes donated by IVF or ICSI patients (three oocytes from young (≤ 30 years) and three oocytes from advanced maternal age (≥ 40 years) patients) undergoing controlled ovarian stimulation. Thus, a total of six maturated oocytes were individually processed for scRNA-seq analysis. The key genes screened from scRNA-seq analysis are confirmed using mouse model. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing infertility treatment at the Yuhuangding Hospital of Yantai underwent ovarian stimulation with FSH and received hCG for final follicular maturation prior to ul-trasound guided oocyte retrieval. We isolated RNA, generated single cell RNA-seq librar-ies (Smart-Seq2) and sequenced by Illumina Hiseq X-ten platform with 150 bp paired-end. Bioinformatics analysis of the sequencing data was done to find the biological processes and key genes that led to the decline in the quality of oocytes with advanced maternal age. To validate the findings, we used mouse model and validated candidate genes by RT-PCR and knockdown experiments. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1439 genes differentially expressed between older and younger women's maturated oocytes (|foldchange|>2, P < 0.05). These genes are significantly enriched with annotations related to transporter activity, cytoskeleton, oxidative stress, catalytic activity, immune function, cellular senescence and biosynthesis. The key candidate gene TOP2B was found by protein interaction network analysis, and knockdown verification on young mouse maturated oocytes showed that TOP2B was a key gene affecting the oocyte quality and disturbing early embryo development. LARGE SCALE DATA Raw data from this study can be accessed through GSE. LIMITATIONS, REASONS FOR CAUTION: The human maturated oocytes used in this study were from patients with different causes of infertility and may affect oocyte gene expression. In addition, the study was based on a lim-ited number of patients, and there are possible natural biological variance existed in human samples. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, we used scRNA-seq to detect global gene transcriptome of maturated oocytes in young and older women. These results are useful to indicate the molecular mechanisms of female ovary aging and establishing a criterion to evaluate the quality of oocytes in women with advanced maternal age. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Key Research and Development Program of China (2018YFC1004304, 2016YFA0100203), Medical and Health Science Technology Development Plan Project of Shandong Province (Grant#. 2017WS566). There are no competing interests.
2019-01-19 | GSE125300 | GEO