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 JC polyomavirus Betapolyomavirus macacae Human gammaherpesvirus 8 Homo sapiens Human immunodeficiency virus 1 Murid gammaherpesvirus 4 Human betaherpesvirus 5 Human alphaherpesvirus 2 Human alphaherpesvirus 1 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:PURPOSE:The 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. METHODS:The method of the study is prospective cohort study. RESULTS:Of 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. CONCLUSIONS:The 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-other
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: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: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:Sigma non-opioid intracellular receptor 1 (sigma-1 receptor), a non-opioid transmembrane protein, is located on cellular mitochondrial membranes and endoplasmic reticulum. Current research has demonstrated that sigma-1 receptor is related to human degenerative diseases. This study is focused on the effects of sigma-1 receptor on the pathophysiological process of diminished ovarian reserve (DOR) and granulosa cells (GCs) apoptosis. Sigma-1 receptor concentration in follicular fluid (FF) and serum were negatively correlated with basal follicle-stimulating hormone (FSH) and positively correlated with anti-mullerian hormone (AMH), antral follicle count (AFC). Sigma-1 receptor reduction in GCs was accompanied by endoplasmic reticulum stress (ERS)-mediated apoptosis in women with DOR. Plasmid transfection was used to establish SIGMAR1-overexpressed and SIGMAR1-knockdown human granulosa-like tumor (KGN) cell and thapsigargin (TG) was used to induce ERS KGN cells. We found that KGN cells treated with endogenous sigma-1 receptor ligand dehydroepiandrosterone (DHEA) and sigma-1 receptor agonist PRE-084 showed similar biological effects to SIGMAR1-overexpressed KGN cells and opposite effects to SIGMAR1-knockdown KGN cells. DHEA may improve DOR patients' pregnancy outcomes by upregulating sigma-1 receptor and downregulating ERS-mediated apoptotic genes in GCs. Thus, sigma-1 receptor may be a potential ovarian reserve biomarker, and ligand-mediated sigma-1 receptor activation could be a future approach for DOR therapy.
| S-EPMC7288944 | biostudies-literature
Project description:With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review.PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [<dehydroepiandrosterone or DHEA or androgens or testosterone > and <ovarian reserve or diminished ovarian reserve or ovarian function >]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed.Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia.Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow.
| S-EPMC3112409 | biostudies-literature