MiR-106a increases granulosa cell viability and is down-regulated in women with diminished ovarian reserve
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ABSTRACT:
ORGANISM(S): Merkel cell polyomavirus Mus musculus Rattus norvegicus Human gammaherpesvirus 8 Human alphaherpesvirus 1 JC polyomavirus Betapolyomavirus macacae Homo sapiens Human immunodeficiency virus 1 Murid gammaherpesvirus 4 Human betaherpesvirus 5 Human alphaherpesvirus 2 Betapolyomavirus hominis human gammaherpesvirus 4 Mus musculus cytomegalovirus 2 Murid betaherpesvirus 1
PROVIDER: GSE111774 | GEO | 2018/03/14
REPOSITORIES: GEO
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Project description:MiR-106a increases granulosa cell viability and is down-regulated in women with diminished ovarian reserve
| PRJNA438137 | ENA
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: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:PurposeThe study aims to determine differences in micro-RNA (miRNA) expression in granulosa (GC) and cumulus cells (CC) between young women with diminished ovarian reserve (DOR) or normal ovarian reserve (NOR). Secondary objective was to identify downstream signaling pathways that could ultimately indicate causes of lower developmental competence of oocytes from young women with DOR.MethodsThe method of the study is prospective cohort study.ResultsOf the miRNA, 125 are differentially expressed in GC between DOR and NOR. Only nine miRNA were different in CC; therefore, we focused analysis on GC. In DOR GC, miR-100-5p, miR-16-5p, miR-30a-3p, and miR-193a-3p were significantly downregulated, while miR-155-5p, miR-192-5p, miR-128-3p, miR-486-5p, miR130a-3p, miR-92a-3p, miR-17-3p, miR-221-3p, and miR-175p were increased. This pattern predicted higher cell proliferation in the DOR GC. The primary pathways include MAPK, Wnt, and TGFbeta.ConclusionsThe miRNA pattern identified critical functions in cell proliferation and survival associated with DOR. GC in women with DOR seems to respond differently to the LH surge.
| S-EPMC6150892 | biostudies-literature
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:BackgroundDuring fertility treatment, diminished ovarian reserve (DOR) is a challenge that can seriously affect a patient's reproductive potential. However, the pathogenesis of DOR is still unclear and its treatment options are limited. This study aimed to explore DOR's molecular mechanisms.MethodsWe used R software to analyze the mRNA microarray dataset E-MTAB-391 downloaded from ArrayExpress, screen for differentially expressed genes (DEGs), and perform functional enrichment analyses. We also constructed the protein-protein interaction (PPI) and miRNA-mRNA networks. Ovarian granulosa cells (GCs) from women with DOR and the control group were collected to perform untargeted metabolomics analyses. Additionally, small molecule drugs were identified using the Connectivity Map database.ResultsWe ultimately identified 138 DEGs. Our gene ontology (GO) analysis indicated that DEGs were mainly enriched in cytokine and steroid biosynthetic processes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), the DEGs were mainly enriched in the AGE (advanced glycation end-product)-RAGE (receptor for AGE) signaling pathway in diabetic complications and steroid biosynthesis. In the PPI network, we determined that JUN, EGR1, HMGCR, ATF3, and SQLE were hub genes that may be involved in steroid biosynthesis and inflammation. miRNAs also played a role in DOR development by regulating target genes. We validated the differences in steroid metabolism across GCs using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We selected 31 small molecules with potentially positive or negative influences on DOR development.ConclusionWe found that steroidogenesis and inflammation played critical roles in DOR development, and our results provide promising insights for predicting and treating DOR.
| S-EPMC7457930 | biostudies-literature
Project description:PurposeTo investigate the biological networks associated with DOR in young women and the subsequent molecular impact on preimplantation embryos.MethodsWhole peripheral blood was collected from patients: young women presenting with diminished ovarian reserve (DOR) and age-matched young women with normal ovarian reserve. Maternal exome sequencing was performed on the NovaSEQ 6000 and sequencing validation was completed using Taqman® SNP Genotyping Assays. Blastocyst global methylome and transcriptome sequencing were also analyzed.ResultsExome sequencing revealed 730 significant DNA variants observed exclusively in the young DOR patients. Bioinformatic analysis revealed a significant impact to the Glucocorticoid receptor (GR) signaling pathway and each young DOR female had an average of 6.2 deleterious DNA variants within this pathway. Additional stratification based on patient age resulted in a cut-off at 31 years for young DOR discrimination. Embryonic global methylome sequencing resulted in only a very small number of total CpG sites with methylation alterations (1,775; 0.015% of total) in the DOR group. Additionally, there was no co-localization between these limited number of altered CpG sites and significant variants, genes, or pathways. RNA sequencing also resulted in no biologically significant transcription changes between DOR blastocysts and controls.ConclusionGR signaling DNA variants were observed in women with early-onset DOR potentially compromising oocyte production and quality. However, no significant downstream effects on biological processes appear to impact the resulting blastocyst. The ability to forecast premature DOR for young women may allow for earlier identification and clinical intervention for this patient population.
| S-EPMC8324723 | biostudies-literature
Project description:BackgroundMounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian reserve in young, infertile women.MethodsOur study included 2276 Korean women who attended a single fertility center in 2016-2018. Women's exposure to air pollution was assessed using concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting.ResultsThe mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM10 was associated with decrease in AMH ratio among total population (β= -0.06, 95% confidence interval: -0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM2.5 were associated with 3% (95% CI: -0.07, 0.00) and 10% (95% CI: -0.18, -0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents.ConclusionsIn a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women's fertility.
| S-EPMC7879617 | biostudies-literature
Project description:BackgroundIn our previous investigation, we revealed a significant increase in the expression of microRNA-6881-3p (miR-6881-3p) in follicular fluid granulosa cells (GCs) from women with diminished ovarian reserve (DOR) compared to those with normal ovarian reserve (NOR). However, the role of miR-6881-3p in the development of DOR remains poorly understood.ObjectiveThis study aimed to elucidate the involvement of miR-6881-3p in the regulation of granulosa cells (GCs) function and the pathogenesis of DOR.Materials and methodsInitially, we assessed the expression levels of miR-6881-3p in GCs obtained from human follicular fluid in both NOR and DOR cases and explored the correlation between miR-6881-3p expression and clinical outcomes in assisted reproduction technology (ART). Bioinformatic predictions and dual-luciferase reporter assays were employed to identify the target gene of miR-6881-3p. Manipulation of miR-6881-3p expression was achieved through the transfection of KGN cells with miR-6881-3p mimics, inhibitor, and miRNA negative control (NC). Following transfection, we assessed granulosa cell apoptosis and cell cycle progression via flow cytometry and quantified target gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Finally, we examined the correlation between target gene expression levels in GCs from NOR and DOR patients and their association with ART outcomes.ResultsOur findings revealed elevated miR-6881-3p levels in GCs from DOR patients, which negatively correlated with ovarian reserve function and ART outcomes. We identified a direct binding interaction between miR-6881-3p and the 3'-untranslated region of the SMAD4. Transfection with miR-6881-3p mimics induced apoptosis in KGN cell. Furthermore, miR-6881-3p expression negatively correlated with both mRNA and protein levels of the SMAD4. The mRNA and protein levels of SMAD4 were notably reduced in GCs from DOR patients, and SMAD4 mRNA expression positively correlated with ART outcomes. In addition, the mRNA levels of FSHR, CYP11A1 were notably reduced after transfection with miR-6881-3p mimics in KGN cell, while LHCGR notably increased. The mRNA and protein levels of FSHR, CYP11A1 were notably reduced in GCs from DOR patients, while LHCGR notably increased.ConclusionThis study underscores the role of miR-6881-3p in directly targeting SMAD4 mRNA, subsequently diminishing granulosa cell viability and promoting apoptosis, and may affect steroid hormone regulation and gonadotropin signal reception in GCs. These findings contribute to our understanding of the pathogenesis of DOR.
| S-EPMC10832098 | biostudies-literature
Project description:IntroductionInsulin resistance (IR) is found in patients with polycystic ovary syndrome (PCOS), but the effects and mechanisms of IR on diminished ovarian reserve (DOR) remain unclear. This study set out to investigate the effects of IR on ovarian reserve; to explore the effects of high concentrations of insulin on the function of ovarian cells in vitro; and to validate the hypothesis that the Gengnianchun recipe (GNC) helps to attenuate DOR caused by IR through reducing the senescence of granulosa cells.MethodsEstrus cycle, follicle count, and sex hormone levels were detected to evaluate ovarian function in mice with IR caused by feeding a high-fat diet (HFD). In addition, KGN cells (human granulosa cell line) were treated with high concentrations of insulin. The staining for senescence-associatedβ-galactosidase (SA-β-gal), cell cycle, and expression levels of mRNA and gene proteins related to cell aging were detected in KGN cells treated with high concentrations of insulin. Mice treated with an HFD were fed metformin, GNC, or saline solution for 6 weeks by oral gavage. HOMA-IR, the area under the curve (AUC) of the oral glucose tolerance test (OGTT), levels of fasting blood glucose (FBG), and fasting serum insulin (FINS) were examined to confirm the IR status. Then estrus cycle, follicle count, and sex hormone levels were detected to evaluate ovarian function. Expression levels of mRNA and gene proteins related to cell aging were detected in the ovarian tissue of mice in each group.ResultsThe results demonstrated that IR reduced murine ovarian reserves, and high doses of insulin caused granulosa cells to senesce. There was a considerable improvement in HFD-induced IR status in the metformin (Met) and GNC treatment groups. In addition, the expression levels of aging-associated biomarkers were much lower in GNC mice than Met mice; and both the latter groups had considerably lower levels than the HFD group. Moreover, higher follicle counts in different stages and shorter diestrus in the Met or GNC groups compared to the HFD group indicated that ovarian aging could be largely reversed.DiscussionThis work showed that: IR impaired ovarian reserve; high concentrations of insulin induced granulosa cell aging; and GNC attenuated ovarian function through inhibiting IR-induced cell aging.
| S-EPMC10016225 | biostudies-literature