Downregulation of Glucose-Energy Metabolism via AMPK Signaling Pathway in Granulosa Cells of Diminished Ovarian Reserve Patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1148147 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glucose metabolism plays a crucial role in the function of granulosa cells (GCs) and the development of follicles. In cases of diminished ovarian reserve (DOR), alterations in these processes can impact female fertility. This study aims to investigate changes in glucose-energy metabolism in GCs of young DOR patients aged 20 to 35 years and their correlation with the onset and progression of DOR. 72 DOR cases and 75 women with normal ovarian reserve (NOR) as controls were included based on the POSEIDON and Bologna criteria. Samples of GCs and follicular fluid (FF) were collected for a comprehensive analysis involving transcriptomics, metabolomics, RT-qPCR, JC-1 staining, and flow cytometry. The study identified differentially expressed genes and metabolites in GCs of DOR and NOR groups, revealing 7 common pathways related to glucose-energy metabolism, along with 11 downregulated genes and 14 metabolites. Key substances in the glucose-energy metabolism pathway, such as succinate, lactate, NADP, ATP, and ADP, showed decreased levels, with the DOR group exhibiting a reduced ADP/ATP ratio. Downregulation of genes involved in glycolysis (HK, PGK, LDH1), the TCA cycle (CS), and gluconeogenesis (PCK) was observed, along with reduced glucose content and expression of glucose transporter genes (GLUT1 and GLUT3) in DOR GCs. Additionally, decreased AMPK pathway activity and impaired mitochondrial function in DOR suggest a connection between mitochondrial dysfunction and disrupted energy metabolism. Above all, the decline in glucose-energy metabolism in DOR is closely associated with its onset and progression. Reduced glucose uptake and impaired mitochondrial function in DOR GCs lead to internal energy imbalances, hindering the AMPK signaling pathway, limiting energy production and supply, and ultimately impacting follicle development and maturation.
2024-10-01 | GSE274832 | GEO
Project description:To investigate the pathogenesis of diminished ovarian reserve, differentially expressed miRNAs in granulosa cells were constructed through miRCURYTM LNA expression Array.
2018-03-14 | GSE111771 | GEO
Project description:Diminished ovarian reserve (DOR) is a challenging diagonosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. In this study, our aim was to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from approximately age-matched egg donors to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development dring an IVF cycle (n=13). Egg donors with normal ovarian reserve comprised the control group (n=13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic difference between the groups. Confirmatory studies were undertaken with qRT-PCR. Multiple significant differences in gene expression were observed between the DOR patients and egg donors.
2011-09-28 | E-MTAB-391 | biostudies-arrayexpress
Project description:Differentially expressed miRNAs in granulosa cell of diminished ovarian reserve (DOR) patients
| PRJNA438139 | ENA
Project description:This group consist of human embryologists from the reproductive medical center for of the 1st affiliated hospital of Anhui Medical University. Our research is specifically focused on women ovarian reserve and the relevant female infertility. By deep sequencing, the current experiment determined the small non-coding RNA profile of cumulus cells from patients with or without diminished ovarian reserve undergoing controlled ovarian stimulation and in vitro fertilization treatment. Ovarian follicles, which are a densely-packed shell of granulosa cells that contains an immature or mature oocyte, are above all responsible for the development, maturation, and release of mature egg for fertilization. They are also responsible for synthesizing and secreting hormones that are essential for follicular development, menstrual and estrous cycle, maintenance of the reproductive tracts and their functions, development of female secondary sex characteristics, and metabolism. During folliculogenesis, ovarian granulosa cells surrounding the oocyte differentiate into mural granulosa cells, involved in gonadal steroidogenesis, and into cumulus cells, which are ovulated with the oocyte at ovulation. In the present study, we described the small non-coding RNA expression profile to characterize the ensemble of both known and novel ncRNAs expressed in cumulus cells from patients with or without Diminished ovarian reserve, by using high-throughput Solexa technology.
2015-11-20 | E-MTAB-3913 | biostudies-arrayexpress
Project description:MiR-106a increases granulosa cell viability and is down-regulated in women with diminished ovarian reserve
| PRJNA438137 | ENA
Project description:Background: Infertility is one of the major health problems and the third most common disease, and diminished ovarian reserve (DOR) is a common cause of infertility. DOR is defined as decreased number or quality of oocytes in reproductive-age women, but the underlying molecular mechanisms remain unclear. Long noncoding RNAs (lncRNAs) has been recognized to play an important role in physiological and pathological processes of the human body, but it is unknown whether lncRNAs are involved in the development of DOR. Methods: The ovarian granulosa cells from infertility women with DOR and normal ovarian reserve (NOR) were obtained and subjected to high-throughput sequencing. A comprehensive bioinformatics analysis was conducted to characterize the mRNAs and lncRNAs expression profiles between DOR and NOR women. Then, the sequencing results were validated by selected randomly lncRNAs using real-time quantitative PCR. Results: A total of 92,853 lncRNAs transcripts were identified between DOR and NOR GCs. Compared with NOR control, 244 lncRNAs were upregulated (53 known and 191 novel) and 222 lncRNAs were downregulated (36 known and 186 novel) in the DOR group. Similarly, 457 differently expressed mRNAs were found between the two groups, with 169 and 288 up- and downregulated respectively. Further functional analysis revealed that differentially expressed genes of mRNA and lncRNA were significantly enriched in various biological processes such as cell adhesion and apoptosis, steroid biosynthesis, and immune system. The results of correlated expression networks between lncRNAs and their predicted target genes uncovered the possible involvement of the thyroid hormone signaling pathway and protein binding, digestion and absorption in the pathogenesis of DOR and showed that SLC16A10 is positively regulated by multiple lncRNAs. In addition, it was verified that the expression patterns of three of the seven selected differentially expressed lncRNAs were consistent with RNA-Seq. Aberrant lncRNAs might be used to develop new diagnostic biomarkers or drugs to target DOR. Conclusion: This study is the first to elucidate the lncRNA and mRNA expression profiles between NOR and DOR patients in the ovarian granulosa cells using sequencing technology. The lncRNAs identified in this study can potentially be novel diagnostic biomarkers and therapeutic targets for DOR.
2024-03-27 | GSE193136 | GEO
Project description:Long noncoding RNAs expression profiles in granulosa of woman with diminished ovarian reserve based on high-throughput sequencing
| PRJNA795091 | ENA
Project description:To investigate the pathogenesis of diminished ovarian reserve, differentially expressed miRNAs in serum were constructed through miRCURYTM LNA expression Array.
2018-03-14 | GSE111773 | GEO
Project description:Faithful execution of developmental programs relies on the acquisition of unique cell identities from pluripotent progenitors, a process governed by combinatorial inputs from numerous signaling cascades that ultimately dictate lineage-specific transcriptional outputs. Despite growing evidence that metabolism is integrated with many molecular networks, how pathways that control energy homeostasis may affect cell fate decisions is largely unknown. Here, we show that AMPK, a central metabolic regulator, plays critical roles in lineage specification. Although AMPK-deficient embryonic stem cells (ESCs) were normal in the pluripotent state, these cells displayed profound defects upon differentiation, failing to generate chimeric embryos and preferentially adopting an ectodermal fate at the expense of the endoderm during embryoid body (EB) formation. AMPK-/- EBs exhibited reduced levels of Tfeb, a master transcriptional regulator of lysosomes, leading to diminished endolysosomal function. Remarkably, genetic loss of Tfeb also yielded endodermal defects, while AMPK-null ESCs over-expressing this transcription factor normalized their differential potential, revealing an intimate connection between Tfeb/lysosomes and germ layer specification. The compromised endolysosomal system resulting from AMPK or Tfeb inactivation blunted Wnt signaling, while up-regulating this pathway restored expression of endodermal markers. Collectively, these results uncover the AMPK pathway as a novel regulator of cell fate determination during differentiation. 2 WT and 2 AMPK DKO ESC lines were differentiated into embryoid bodies (EBs) for various lengths of time (2, 4, 8, and 12 days) in high and low glucose conditions. Both ESC and EB samples were profiled by mRNA-seq to examine how global gene expression changes associated with ESC differentiation are affected by AMPK deletion.
2016-03-09 | E-GEOD-77705 | biostudies-arrayexpress