Novel PGK1 determines AR stability dependent on Spk2 and reprograms granular cell glucose metabolism to facilitate ovulation dysfunction
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ABSTRACT:
PROVIDER: PRJNA612177 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11294051_1.fastq.gz | Fastqsanger.gz | |||
| SRR11294051_2.fastq.gz | Fastqsanger.gz | |||
| SRR11294052_1.fastq.gz | Fastqsanger.gz | |||
| SRR11294052_2.fastq.gz | Fastqsanger.gz | |||
| SRR11294053_1.fastq.gz | Fastqsanger.gz |
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Project description:Ovulation disorder is the main characteristic of polycystic ovary syndrome (PCOS), but the concrete molecular mechanism is unclear. Phosphoglycerate kinase 1 (PGK1) plays an important role in the process of glycolytic cycles. Androgen and androgen receptor (AR) are considered as one of the critical factors in the prevalence of hyperandrogenemia and follicular development, and whether PGK1 participates in the metabolic reaction via AR in PCOS remains vague. PGK1 and AR proteins were highly expressed in PCOS luteinized granulosa cells and the PCOS-like mice ovary tissues. PGK1 increased lactate levels and deteriorated PCOS-like mouse metabolic disorder, and importantly, the phenotype of PCOS-like mice was rescued by PTX (paclitaxel) and the PGK1 and AR protein levels also decreased in the ovary. We demonstrated that PGK1 promoted AR translocation into the nuclear, and PGK1 was dependent on the E3 ligase Skp2 to repress the AR ubiquitination to improve the AR stability. In addition, we found that follicular development critical genes MAP2K6, KLF15, LRIG3 and MYOF were regulated by the PGK1-AR axis in the RNA-seq data, and axis also mediated cell proliferation and apoptosis. This study highlights the glycolysis key gene PGK1 to regulate metabolism in granular cell result in etiology of the PCOS. The PGK1-AR axis might provide a new therapy target of PCOS
2020-10-28 | GSE146856 | GEO
Project description:BackgroundDisordered folliculogenesis is a core characteristic of polycystic ovary syndrome (PCOS) and androgen receptors (ARs) are closely associated with hyperandrogenism and abnormalities in folliculogenesis in PCOS. However, whether the new AR binding partner phosphoglycerate kinase 1 (PGK1) in granulosa cells (GCs) plays a key role in the pathogenesis of PCOS remains unclear.MethodsWe identified the new AR binding partner PGK1 by co-IP (co-immunoprecipitation) in luteinized GCs, and reconfirmed by co-IP, co-localization and GST pull down assay, and checked PGK1 expression levels with qRT-PCR and western blotting. Pharmaceuticals rescue assays in mice, and metabolism assay, AR protein stability and RNA-seq of PGK1 targets in cells proved the function in PCOS.FindingsPGK1 and AR are highly expressed in PCOS luteinized GCs and PCOS-like mouse ovarian tissues. PGK1 regulated glucose metabolism and deteriorated PCOS-like mouse metabolic disorder, and paclitaxel rescued the phenotype of PCOS-like mice and reduced ovarian PGK1 and AR protein levels. PGK1 inhibited AR ubiquitination levels and increased AR stability in an E3 ligase SKP2-dependent manner. Additionally, PGK1 promoted AR nuclear translocation, and RNA-seq data showed that critical ovulation-related genes were regulated by the PGK1-AR axis.InterpretationPGK1 regulated GCs metabolism and interacted with AR to regulate the expression of key ovulation genes, and also mediated cell proliferation and apoptosis, which resulted in the etiology of PCOS. This work highlights the pathogenic mechanism and represents a novel therapeutic target for PCOS.FundingNational Key Research and Development Program of China; National Natural Science Foundation of China grant.
| S-EPMC7581881 | biostudies-literature
Project description:The present study aimed at studying the rainbow trout egg transcriptome using 9152-cDNA microarrays after natural or controlled ovulation. The analysis of egg transcriptome after natural or controlled ovulation led to the identification of 26 genes. We observed that both hormonal induction and photoperiod control of ovulation induced significant changes in the egg mRNA abundance of specific genes. We demonstrate that hormonal induction of ovulation has an impact on the egg mRNA abundance of specific genes even though the resulting effects on the developmental potential of the egg is so far unknown. In addition, we also identified 1 gene exhibiting a differential mRNA abundance in eggs of varying developmental potential. Analysis of egg transcriptome after natural ovulation (4 samples), photoperiod-controlled ovulation (14 samples), and hormonally-induced ovulation (11 samples).
2010-07-01 | E-GEOD-5928 | biostudies-arrayexpress
Project description:During exocytosis, a Ca2+ increase arises in close vicinity of secretory granules which is strictly prevented in resting cells. Granular Ca2+ homeostasis and its role in granular exocytosis are not well understood.
2018-08-14 | GSE110646 | GEO
Project description:The present study aimed at studying the rainbow trout egg transcriptome using 9152-cDNA microarrays after natural or controlled ovulation. The analysis of egg transcriptome after natural or controlled ovulation led to the identification of 26 genes. We observed that both hormonal induction and photoperiod control of ovulation induced significant changes in the egg mRNA abundance of specific genes. We demonstrate that hormonal induction of ovulation has an impact on the egg mRNA abundance of specific genes even though the resulting effects on the developmental potential of the egg is so far unknown. In addition, we also identified 1 gene exhibiting a differential mRNA abundance in eggs of varying developmental potential. Keywords: Egg quality-dependent
2006-10-03 | GSE5928 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE40471: Maternal slimming reprograms metabolic gene expression in mice offspring (NimbleGen expression) GSE40477: Maternal slimming reprograms metabolic gene expression in mice offspring (NimbleGen methylation) GSE40478: Maternal slimming reprograms metabolic gene expression in mice offspring (mRNA-Seq) Refer to individual Series
2012-08-30 | E-GEOD-40479 | biostudies-arrayexpress
Project description:Running title: More insights into ovulation Purpose:Ovulation is the process by which mature follicles release fertilized oocytes under the stimulation of gonadotropin. This involves the precise interaction and destiny of various cells in the follicle. Granulosa cells (GCs) are the only cells that recognize and respond to ovulation LH (or HCG) signals. Therefore, the classification and deep interpretation of genes in GCs under LH surge stimulation is the key to understand ovulation. Methods: In this study, RNA-seq, Q-PCR, Western blot, gene knockout, gene knockout and other experimental techniques were used to conduct trend and classification analysis of the genes regulated by ovulation signal of LH at the cellular and individual levels. Genes that may be involved in ovulation were screened, identified and were selected for functional verification. Results:(1) Firstly, 7104 and 347 mRNA and Long noncoding RNA (LncRNA) that may be involved in ovulation activity were screened at the gene level by transcriptome sequencing technology, respectively. According to gene expression, they were divided into activated, inhibited and transient activated gene expression patterns. 44 secreted proteins, 62 transcription factors, 22 periodic expression characteristic genes, 10 ovulation process unknown genes, 16 LncRNA-target gene cis pair combinations and 41 highly expressed LncRNA were identified and listed in the three models;(2) The functions of LncRNA Gm12840 and Gm20186 were studied at the cellular level. The results showed that knockdown Gm12840/20186 not only inhibited the proliferation and hormone synthesis of GCs, but also induced cell apoptosis;(3) The function of LncRNA Gm12840 was further studied in mice, and Gm12840 knockout mice were constructed by CRISPR/CAS9 technology: Results It was found that Gm12840 knockout significantly increased the number of antral follicles and ovulation, and significantly inhibited the number of atretic follicles and antral follicles not discharged after ovulation. Gm12840 knockout significantly increased litter size at 2-3 months of age, but also significantly inhibited litter size at 7-9 months of age. Meanwhile, Gm12840 knockout also significantly inhibited the number of follicles growing in the ovary of 11-month-old mice;(4) Finally, transcriptomic sequencing analysis of wilt-type and Gm12840-/- mouse GCs showed 349 genes were differentially expressed. KEGG enrichment analysis and WB results showed that Gm12840 knockout enhanced mTOR and MAPK signals. Conclusions:The above results screened and identified genes with potential research value during ovulation process, and took LncRNA Gm12840 as an example to verify their functions at the cell and individual levels, providing reference for further revealing the ovulation process.
2024-08-27 | GSE182965 | GEO
Project description:Running title: More insights into ovulation Purpose:Ovulation is the process by which mature follicles release fertilized oocytes under the stimulation of gonadotropin. This involves the precise interaction and destiny of various cells in the follicle. Granulosa cells (GCs) are the only cells that recognize and respond to ovulation LH (or HCG) signals. Therefore, the classification and deep interpretation of genes in GCs under LH surge stimulation is the key to understand ovulation. Methods: In this study, RNA-seq, Q-PCR, Western blot, gene knockout, gene knockout and other experimental techniques were used to conduct trend and classification analysis of the genes regulated by ovulation signal of LH at the cellular and individual levels. Genes that may be involved in ovulation were screened, identified and were selected for functional verification. Results:(1) Firstly, 7104 and 347 mRNA and Long noncoding RNA (LncRNA) that may be involved in ovulation activity were screened at the gene level by transcriptome sequencing technology, respectively. According to gene expression, they were divided into activated, inhibited and transient activated gene expression patterns. 44 secreted proteins, 62 transcription factors, 22 periodic expression characteristic genes, 10 ovulation process unknown genes, 16 LncRNA-target gene cis pair combinations and 41 highly expressed LncRNA were identified and listed in the three models;(2) The functions of LncRNA Gm12840 and Gm20186 were studied at the cellular level. The results showed that knockdown Gm12840/20186 not only inhibited the proliferation and hormone synthesis of GCs, but also induced cell apoptosis;(3) The function of LncRNA Gm12840 was further studied in mice, and Gm12840 knockout mice were constructed by CRISPR/CAS9 technology: Results It was found that Gm12840 knockout significantly increased the number of antral follicles and ovulation, and significantly inhibited the number of atretic follicles and antral follicles not discharged after ovulation. Gm12840 knockout significantly increased litter size at 2-3 months of age, but also significantly inhibited litter size at 7-9 months of age. Meanwhile, Gm12840 knockout also significantly inhibited the number of follicles growing in the ovary of 11-month-old mice;(4) Finally, transcriptomic sequencing analysis of wilt-type and Gm12840-/- mouse GCs showed 349 genes were differentially expressed. KEGG enrichment analysis and WB results showed that Gm12840 knockout enhanced mTOR and MAPK signals. Conclusions:The above results screened and identified genes with potential research value during ovulation process, and took LncRNA Gm12840 as an example to verify their functions at the cell and individual levels, providing reference for further revealing the ovulation process.
2024-08-27 | GSE182964 | GEO
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2016-09-30 | GSE80966 | GEO
Project description:To investigate the transcriptomic profile of in vivo and ex vivo ovulation systems
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