Comprehensive molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155489 | GEO | 2020/09/08
REPOSITORIES: GEO
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Project description:Objective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis. Design: Prospective case - control study. Setting: University Hospital. Patients: 25 patients undergoing IVF-ICSI treatment. Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean). Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients. Conclusions: Different molecular pathways are associated with PCOS in Lean and Obese individuals, as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS. We used microarrays to study the gene expression of human cultured cumulus cells. We compared the genes expression of lean PCOS, Obese PCOS, lean controls and obese controls. Different molecular pathways are associated with PCOS in Lean and Obese patients. Keywords: disease state analysis
2008-03-27 | GSE10946 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that is characterized by increased circulating androgen levels, anovulatory infertility, and frequently, insulin resistance and hyperinsulinemia.The abnormity of oocyte nuclear maturity is the main reason for anovulatory infertility and pregnancy loss in PCOS patients.The bidirectional exchanges between oocyte and contiguous CCs are important for oocyte competence acquisition, early embryonic development and CC expansion.Gene expression profiles of CCs has been suggested to predict embryo development and pregnancy outcome. We used microarrays to detail the global programme of gene expression of CCs isolated from oocytes at metaphase I (CCMI) and metaphase II (CCMII) stage under controlled ovarian stimulation (COS) cycle in PCOS patients. Cumulus cells were isolated from oocyte at stage metaphase 1(MI)and stage metaphase II (MII) of PCOS patients for RNA extraction and hybridization on Affymetrix microarrays. For microarray analysis, we used three chips for each CC category. That is, CCMI1,CCMI2,CCMI3,CCMII1,CCMII2 and CCMII3.
2013-06-05 | E-GEOD-40400 | biostudies-arrayexpress
Project description:Polycystic ovary syndrome (PCOS) is the most common and heterogeneous endocrine disorder in women of reproductive age.Depending on different criteria and populations,the prevalence of PCOS ranges from 6 to 8% with the NIH criteria, and up to 20% with the Rotterdam criteria.Further, it accounts for approximately 75% of anovulatory infertility.Circular RNAs (circRNAs) mediate the posttranscriptional regulation of multiple genes by functioning as microRNA (miRNA) sponges. This study aimed to detect the novel expression of circRNAs in the cumulus cells (CCs) of PCOS patients and their potential significance in the pathogenesis of PCOS.
2020-02-14 | GSE145296 | GEO
Project description:Objective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis. Design: Prospective case - control study. Setting: University Hospital. Patients: 25 patients undergoing IVF-ICSI treatment. Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean). Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients. Conclusions: Different molecular pathways are associated with PCOS in Lean and Obese individuals, as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS. We used microarrays to study the gene expression of human cultured cumulus cells. We compared the genes expression of lean PCOS, Obese PCOS, lean controls and obese controls. Different molecular pathways are associated with PCOS in Lean and Obese patients. Experiment Overall Design: Cumulus cells obtained from woman undergoing IVF/ICSI. Following oocyte retrieval, cumulus cells were stripped from the oocyte, in preparation for the ICSI process, with a micropipette. After 48h in culture the cumulus cells were collected for RNA extraction and hybridization on Affymetrix microarrays. We compered the expression profile of 4 groups - lean PCOS, obese PCOS, lean controls and obese controls.
2008-06-11 | E-GEOD-10946 | biostudies-arrayexpress
Project description:Purpose:To examine different expression profiles of lncRNAs and mRNAs in ovarian granulosa cells (GCs) in PCOS patients and controls Patients:6 GCs samples in each group were subjected to high-thoughput sequencing Results:54,615 lncRNAs and 123,141 mRNAs were detected in this high-thoughput sequencing, and we identified 1049 differential expressed lncRNAs and 3246 mRNAs (fold-change≧2, P-value<0.05). So far, we found 7 lncRNAs and 3mRNAs were validated consistent with sequence profile which were selected, randomly. There is still a large part that we have not verified yet. Conclusion: Our study provides the detail analysis of GCs transcriptomes, generated by high-thoughput technology. This report also provides a framework for comparative investigations of PCOS. Our results revealed the expression of lncRNAs, mRNAs and part of circRNAs in PCOS, after more in-depth research in future, it can provide basic datas for studying the pathogenesis of PCOS.
2023-04-20 | GSE173160 | GEO
Project description:Polycystic ovary syndrome (PCOS) is the most common complex endocrine and metabolic disease in women of reproductive age. It is characterized by anovulatory infertility, hormone disorders, and polycystic ovarian morphology. Regarding the importance of granulosa cells (GCs) in the pathogenesis of PCOS, few studies have investigated the etiology at a single “omics” level, such as with an mRNA expression array or methylation profiling assay, but this can provide only limited insights into the biological mechanisms. Here, genome-wide DNA methylation together with lncRNA-miRNA-mRNA profiles were simultaneously detected in GCs of PCOS cases and controls. A total of 3579 lncRNAs, 49 miRNAs, 669 mRNAs, and 890 differentially methylated regions (DMR)-associated genes were differentially expressed between PCOS cases and controls. Pathway analysis indicated that these differentially expressed genes were commonly associated with steroid biosynthesis and metabolism-related signaling, such as glycolysis/gluconeogenesis. In addition, we constructed ceRNA networks and identified some known ceRNA axes, such as lncRNAs-miR-628-5p-CYP11A1/HSD17B7. We also identified many new ceRNA axes, such as lncRNAs-miR-483-5p-GOT2. Interestingly, most ceRNA axes were also closely related to steroid biosynthesis and metabolic pathways. These findings suggest that it is important to systematically consider the role of reproductive and metabolic genes in the pathogenesis of PCOS.
2021-03-08 | GSE168404 | GEO
Project description:Aberration in miRNA expression or DNA methylation is a causal factor for numerous pathological conditions including polycystic ovarian syndrome PCOS, a common endocrine disorders and leading cause of infertility. The epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. Our study identifies epigenetic alternation in ovarian granulosa cells from PCOS patients and helps to reveal the pathogenesis of PCOS.
2019-10-09 | GSE138573 | GEO
Project description:Polycystic ovary syndrome (PCOS) is typically characterized by a polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction, and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes; however, the poor quality of oocytes leads to lower fertilization and implantation rates, decreased pregnancy rates, and increased miscarriage rates. The complex molecular mechanisms underlying PCOS and the poor quality of oocytes remain to be elucidated. We obtained matched oocytes and cumulus cells (CCs) from PCOS patients, compared them with age-matched controls, and performed RNA sequencing analysis to explore the transcriptional characteristics of their oocytes and CCs. Moreover, we validated our newly confirmed candidate genes for PCOS by immunofluorescence. Unsupervised clustering analysis showed that the overall global gene expression patterns and transposable element (TE) expression profiles of PCOS patients tightly clustered together, clearly distinct from those of controls. Abnormalities in functionally important pathways are found in PCOS oocytes. Notably, genes involved in microtubule processes, TUBB8 and TUBA1C, are overexpressed in PCOS oocytes. The metabolic and oxidative phosphorylation pathways are also dysregulated in both oocytes and CCs from PCOS patients. Moreover, in oocytes, differentially expressed TEs are not uniformly dispersed in human chromosomes. Endogenous retrovirus 1 (ERV1) elements located on chromosomes 2, 3, 4, and 5 are rather highly upregulated. Interestingly, these correlate with the most highly expressed protein-coding genes, including tubulin-associated genes TUBA1C, TUBB8P8, and TUBB8, linking the ERV1 elements to the occurrence of PCOS. Our comprehensive analysis of gene expression in oocytes and CCs, including TE expression, revealed the specific molecular features of PCOS. The aberrantly elevated expression of TUBB8 and TUBA1C and ERV1 provides additional markers for PCOS and may contribute to the compromised oocyte developmental competence in PCOS patients. Our findings may also have implications for treatment strategies to improve oocyte maturation and the pregnancy outcomes for women with PCOS.
| S-EPMC8450412 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by increased ovarian androgen production, arrested follicle development, and is frequently associated with insulin resistance. These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. To examine whether the perturbations in follicle growth and the intrafollicular environment affects development of the mature PCOS oocyte, genes that are differentially expressed in PCOS compared to normal oocytes were defined using microarray analysis. This analysis detected approximately 8000 transcripts. Hierarchical clustering and principal component analysis revealed differences in global gene expression profiles between normal and PCOS oocytes. 374 genes had a statistically-significant increase or decrease in mRNA abundance in PCOS oocytes. A subset of these genes was associated with chromosome alignment and segregation during mitosis and/or meiosis, suggesting that increased mRNAs for these proteins may negatively affect oocyte maturation and/or early embryonic development. Of the 374 differentially expressed genes, 68 contained putative androgen receptor, retinoic acid receptor, and/or peroxisome proliferating receptor gamma binding sites, including 9 of the genes involved in chromosome alignment and segregation. These analyses demonstrated that normal and PCOS oocytes that are morphologically indistinguishable and of high quality exhibit different gene expression profiles. Furthermore, altered mRNA levels in the PCOS oocyte may contribute to defects in meiosis and/or mitosis which might impair oocyte competence for early development and therefore contribute to poor pregnancy outcome in PCOS. Experiment Overall Design: A single MII oocyte, defined by one polar body in the perivitelline space and no visible nuclear structure in the cytoplasm, was collected from 6 individual NL and 6 individual PCOS ovaries, placed immediately in TRIzol (Sigma, St. Louis MO), and stored at -80 C until further study. Total RNA was isolated from each oocyte and subjected to three rounds of linear amplification with the Ovation Biotin RNA Amplification and Labeling System (NuGen Technologies, San Carlos CA) per the manufacturerâs instructions. RNA from the GeneChip Eukaryotic Poly-A RNA Control Kit (Affymetrix, Santa Clara CA) was amplified and labeled under the same conditions for a positive control. Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray chips (Affymetrix, Santa Clara, CA) were hybridized at the University of Pennsylvania Microarray Core Facility. Briefly, the linear-amplified, biotin-labled cDNA from 6 NL (N1-N6) and 6 PCOS (P1-P6) oocytes was hybridized to individual Affymetrix U133 chips. The fluorescence intensity of each chip was normalized to a trimmed mean signal of 150. Each transcript on the U133 chip was defined as present or absent in each oocyte sample using the Affymetrix Microarray Suite 5.0.
2008-06-14 | E-GEOD-5850 | biostudies-arrayexpress
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