Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE181106 | GEO | 2022/04/01
REPOSITORIES: GEO
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Project description:Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve
| PRJNA750720 | ENA
Project description:LncRNAs and mRNAs profiling of gonadotropin-stimulated granulosa cells from PCOS patients and controls (women with normal ovarian reserve)
2020-03-05 | GSE95728 | GEO
Project description:BackgroundIn recent years, the prevalence of Alzheimer's disease (AD) has increased, which places a great burden on society and families and creates considerable challenges for medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA) adenine methylation is a novel biomarker and is abundant in the brain, but less common in AD. We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls (NCs) in China.AimTo analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.MethodsA total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and 147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age- and sex-matched were included in our study. All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination. Apolipoprotein E (APOE) genotypes were measured through agarose gel electrophoresis. Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patients with 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.ResultsOur ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs (P = 0.002; < 0.05). And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting. There were significant differences between the two groups, which indicated that the leukocyte m6A DNA levels were different (P = 0.005; < 0.05). The m6A level was approximately 8.33% lower in AD patients than in NCs (mean 0.011 ± 0.006 vs 0.012 ± 0.005). A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population (r = 0.143, P = 0.01; < 0.05). However, no relationship was found with APOE ε4 (P = 0.633, > 0.05). Further studies should be performed to validate these findings.ConclusionOur results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33% in China.
| S-EPMC8771380 | biostudies-literature
Project description:PURPOSE:To evaluate the relationship between apoptosis of granulosa cells in women with normal ovarian reserve versus diminished ovarian reserve, and relate that to follicular fluid hormones, and to clinical outcomes. METHODS:A prospective cohort study was initiated between October 2015 and June 2016 involving a total of 164 women undergoing IVF/ICSI cycles at a single IVF center. Mural and cumulus granulosa cells, and follicularfluid were collected during oocyte retrieval. Annexin V-FITC/PI apoptosis staining and flow cytometryanalysis were performed to evaluate apoptosis rate of mural granulosa cells and cumulus cells. Follicularfluid hormones were measured by ECLIA. Laboratory and clinical outcomes were analyzed. RESULTS:In mural granulosa cells, early, late and total apoptosis rates were significantly increased in women with diminished ovarian reserve when compare to women with normal ovarian reserve, along with lower AMHand progesterone levels (but higher estradiol levels) in follicular fluid. Early apoptosis rate of cumulus cellswas significantly higher in the non-pregnant group. The apoptosis rate of mural cells was negativelycorrelated with parameters related to ovarian response, oocyte yield, MII egg number, 2pn cleavagenumber, D3 good embryos number, blastocyst formation rate and frozen embryos number. A positivecorrelation was found between mural granulosa cell apoptosis and age. CONCLUSION:A significantly higher apoptosis rate of mural granulosa cells was correlated with worse ovarian response, with fewer egg and embryo numbers in IVF/ICSI, as well as with age. Early apoptosis rate of cumulus cellsmight also have influence on clinical pregnancy.
| S-EPMC6602993 | biostudies-literature
Project description:Limited research has explored the associations between microRNAs (miRNA) and diminished ovarian reserve (DOR). The study aimed to identify differentially expressed miRNAs in follicular fluid exosomes from women with DOR compared to normal ovarian reserve (NOR) and investigate their role in the proliferation and apoptosis of the human ovarian granulosa tumor cell line KGN.
2024-06-01 | GSE238177 | GEO
Project description:Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and 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 during an IVF cycle (n = 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n = 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RT-PCR (qRT-PCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRT-PCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value = 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value = 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology.
| S-EPMC3378309 | biostudies-literature
Project description:Objective(s)To evaluate the association between neighborhood disadvantage and ovarian reserve stratified by body mass index (BMI).DesignCross-sectional cohort study.SettingSingle academic medical center.Patient(s)A total of 193 healthy reproductive-age women with regular menstrual cycles in the St. Louis, Missouri metropolitan area.Intervention(s)Residence in a disadvantaged neighborhood.Main outcome measure(s)Ovarian reserve as assessed by ovarian antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) concentration.Result(s)Women (n = 193) ranged from 20 to 44 years. The majority had overweight or obesity (59%, n = 117) with mean BMI of 28±7 kg/m2. Forty-eight women lived in the most disadvantaged neighborhood quartile, of which 75% had overweight or obesity, compared with 54% of the 145 women living in the 3 less disadvantaged neighborhood quartiles. When controlling for age, race, and smoking status, women with overweight or obesity living in the most disadvantaged neighborhoods had significantly lower AMH compared with those living in the less disadvantaged neighborhoods. Antral follicle count did not differ among women with overweight or obesity by neighborhood of residence. Neighborhood disadvantage was not associated with ovarian reserve by AFC or AMH in women with normal weight or underweight status.Conclusion(s)Living in a socioeconomically deprived area is associated with lower markers of ovarian reserve among women with an elevated BMI.
| S-EPMC10079614 | biostudies-literature
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:BackgroundInfertility is a global reproductive-health problem, and diminished ovarian reserve (DOR) is one of the common causes of female infertility. Long noncoding RNAs (lncRNAs) are crucial regulators of numerous physiological and pathological processes in humans. However, whether lncRNAs are involved in the development of DOR remains to be elucidated.MethodsOvarian granulosa cells (OGCs) extracted from infertile women with DOR and from women with normal ovarian reserve (NOR) were subjected to high-throughput sequencing. Comprehensive bioinformatics analysis was conducted to identify the differential expression of messenger RNAs (mRNAs) and lncRNAs. Sequencing results were validated by the selection of lncRNAs and mRNAs using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsCompared with the NOR group, a total of 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 mRNAs had differential expression between the two groups. Of these, 169 were upregulated and 288 were downregulated. Bioinformatics analysis revealed that the differentially expressed genes of mRNA and lncRNAs were considerably enriched in "cell adhesion and apoptosis", "steroid biosynthesis", and "immune system". A co-expression network comprising lncRNAs and their predicted target genes revealed the possible involvement of the "thyroid hormone signaling pathway" and "protein binding, digestion and absorption" in DOR pathogenesis. The expression of SLC16A10 was positively regulated by multiple lncRNAs. After RT-qPCR validation of seven differentially expressed lncRNAs and mRNAs, respectively, the expression of lncRNA NEAT1, GNG12, ZEB2-AS1, and mRNA FN1, HAS3, RGS4, SUOX were in accordance with RNA-sequencing.ConclusionsWe presented the first data showing that the expression profiles of lncRNA and mRNA in OGCs between NOR and DOR patients using RNA sequencing. The lncRNAs and mRNAs that we identified may serve as novel diagnostic biomarkers for patients with DOR.
| S-EPMC9617369 | biostudies-literature
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