Alternative Splicing Variants of Androgen Receptor Altered insulin resistance Gene expression in Human Ovarian Granulosa Cell
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PROVIDER: PRJNA433307 | ENA |
REPOSITORIES: ENA
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Project description:Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, of which the morbidity among women aging from 18 to 44 years old can be as high as 10%. Insulin resistance is an important characteristic of PCOS and affects approximately 65-70% of women with PCOS. Our previous work identified two AR alternative splicing variants (ASVs) in human granulosa cells (hGCs), Insertion (Ins) and deletion (Del) isoforms, takes up 62% of PCOS specifically. Both isoforms display altered genome-wide recruited genes and genes expressions which are tightly associated with steroidogenesis, folliculogenesis and ovulation. However, the molecular regulatory mechanism of ASVs in hGCs of insulin resistance needs to be illustrated.
2019-02-01 | GSE110252 | GEO
Project description:Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and use of a vertebrate 'insulin-free' model to identify insulin-independent modulators of glucose metabolism. insulin knockout zebrafish recapitulate core characteristics of diabetes and survive only up to larval stages. Utilizing a highly efficient endoderm transplant technique, we generated viable chimeric adults that provide the large numbers of insulin mutant larvae required for our screening platform. Using glucose as a disease-relevant readout, we screened 2233 molecules and identified 3 that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels. Our study proposes therapeutic roles for androgen signaling in diabetes and, more broadly, offers a novel in vivo model for rapid screening and decoupling of insulin-dependent and -independent mechanisms.
2018-12-13 | PXD012027 | Pride
Project description:Excessive androgen production is a hallmark of human and bovine ovarian disorders, and our lab has identified a naturally-occurring bovine model with excess follicular fluid androstenedione (A4) without a proportional estrogen increase. Granulosa cell populations from both the control, Low A4 follicles and the abnormal, High A4 follicles were isolated. Total RNA was extracted from those granulosa cells and submitted to the University of Nebraska Medical Center Microarray Core Facility for transcriptome quantification using Affymetrix Bovine GeneChip Gene 1.0 ST Arrays. The orignal Affymetrix .CEL files and the normalized linear expression data are included in this submission.
2019-04-30 | GSE97017 | GEO
Project description:Considering the well-documented importance of androgens in the female reproductive system and particularly in maintenance of the ovarian follicular reserve, follicle growth and granulosa cell proliferation, we hypothesized that activation of the androgen receptor in granulosa cells with DHT induces significant changes in gene transcription. To determine the AR-regulated gene transcriptome in mouse granulosa cells, we treated female mice aged 18 weeks (n=5) with an introperitoneal injection of dihydrotestosterone (DHT, 29 mcg) in a vehicle of 90% sesame oil and 10% ethanol in a total volume of 100 microliters. 18 hours later, granulosa cells were harvested and mRNA was isolated for RNA sequencing. Surprisingly, no genes were differentially expressed in the granulosa cells obtained from DHT-treated compared with vehicle-treated mice. We then assessed the AR-regulated transcriptome in DHT-treated human granulosa-derived KGN cells. After 24 hours of serum starvation, KGN cells were treated with 25 nM DHT or ethanol for 12 hours in five independent experiments, then RNA was extracted for RNA sequencing. In paired analysis to eliminate inter-experimental variability, 173 genes were differentially expressed in DHT-treated compared with vehicle-treated cells. Of these, 125 genes were upregulated by DHT and 48 genes were downregulated by DHT. However, the fold change in expression was very small (ranging from 0.87 to 1.37, DHT vs vehicle). Although these differences were statistically signficant in paired analysis, they are unlikely to be of biological significance due to such small fold changes in expression. We conclude that AR likely has negligible gene-transcription activity in granulosa cells. Importantly, these experiments were not designed to capture any changes in non-coding RNAs.
2020-09-19 | GSE158218 | GEO
Project description:Maternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation (MAP) procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid (PA) and stearic acid (SA) reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of PA, oleic acid (OA), and SA at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.
2020-11-21 | GSE161914 | GEO
Project description:high concentration of insulin treated human ovarian granulosa cells(KGN cells)
| PRJNA925474 | ENA
Project description:This study reports androgen-induced gene expression in granulosa cells of the ovary and provides a molecular insight of how androgens regulate granulosa cell gene expression through modulating the epigenetic mark H3K27me3.
2020-06-19 | GSE152791 | GEO
Project description:This study reports androgen-induced gene expression in granulosa cells of the ovary and provides a molecular insight of how androgens regulate granulosa cell gene expression through modulating the epigenetic mark H3K27me3.
2020-06-19 | GSE152727 | GEO
Project description:Granulosa cells abnormalities are one of the characteristics of premature ovarian insufficiency (POI). Abnormal expression of serine/arginine-rich splicing factor 1 (SRSF1) can causes a variety of diseases, but the role of SRSF1 in mouse granulosa cells has been poorly reported. In this study, we found that SRSF1 was expressed in the nuclei of both mouse oocytes and granulosa cells. Specific knockout of SRSF1 in granulosa cells was performed using Foxl2-creERT2 mice, and morphological staining showed that follicular development was blocked. In addition, granulosa cell proliferation decreased and cell apoptosis increased. The differential gene Gene Ontology (GO) analysis of RNA-Seq results showed abnormal expression of DNA repair, cell killing and other signaling pathways. Alternative splicing (AS) analysis showed that SRSF1 affected DNA damage in granulosa cells by regulating genes related to DNA repair. In conclusion, SRSF1 in granulosa cells affects female reproduction by controlling the development of follicles through regulating granulosa cell DNA repair related genes.
2024-01-01 | GSE228975 | GEO
Project description:Purpose polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of childbearing age. It is characterized by follicular dysplasia and hyperandrogenemia. Insulin resistance plays an important role in the development of PCOS.However, the mechanism of regulation and interaction between insulin resistance and follicle development remains unclear.The aim of this study was to identify differential genes associated with follicle development in cumulus granulosa cells in PCOS patients with insulin resistance compared with controls. Methods In this study, RNA-seq, bioinformatics analysis and reverse transcription qPCR (RT-qPCR) were used to analyze the gene expression in cumulus granulosa cells.A total of seven cDNA libraries were constructed from three PCOS samples and four control samples.3 μg of RNA was used as starting material for each sample.Ribosomal RNA was removed using the Epicentre rigo-zero ™ Gold Kit (Epicentre, Illumina, Madison, WI, USA). Results Compared with the control group, there were 2233 DEGs in the PCOS group, including 1158 up-regulated genes and 1075 down-regulated genes. Some different expression patterns were observed in the two groups.The next series of experiments verified the effect of some genes on oocyte development. Conclusion Our study showed that the differential expression of transcriptome in cumulus granulosa cells could affect the growth, development and maturation of oocytes.Meanwhile, the results of RT-PCR and Elisa showed that the expression of renin angiotensin system was changed in PCOS patients with insulin resistance, and these changes could affect oocyte maturation and excretion through cumulus granulosa cells.
2023-10-01 | GSE216609 | GEO