Identify urinary exosome microRNAs that are unique to premature ovarian insufficiency
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205700 | GEO | 2022/09/28
REPOSITORIES: GEO
Similar Datasets
Project description:Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone (FSH). Though POI affects many aspects of women’s health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch chain amino acid (BCAA) insufficiency related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57 B6 mice. A mechanism study revealed that the BCAA insufficiency induced POI is associated with abnormal activation of the ceramide-ROS axis and consequent impairment of ovarian granulosa cell function. Significantly, dietary supplement of BCAA prevented the development of ROS-induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.
2023-03-28 | GSE215358 | GEO
Project description:Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism. Premature ovarian insufficiency has few known genetic causes but in familial cases a genetic link is often suspected. A large consanguineous family with three female affected with POI was investigated. All samples including 3 affected and 5 unaffecd underwent whole genome SNP genotyping using Affymetric Axiom_GW_Hu_SNP array. Linkage analysis was carried out using HomozygosityMapper and Allegro softwares.Linkage analysis mapped the disease phenotype to long arm of chromosome 20. Sequence data analysis of potential candidate genes failed to detect any pathogenic variant.
2014-03-20 | GSE56043 | GEO
Project description:Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism. Premature ovarian insufficiency has few known genetic causes but in familial cases a genetic link is often suspected. A large consanguineous family with three female affected with POI was investigated. All samples including 3 affected and 5 unaffecd underwent whole genome SNP genotyping using Affymetric Axiom_GW_Hu_SNP array. Linkage analysis was carried out using HomozygosityMapper and Allegro softwares.Linkage analysis mapped the disease phenotype to long arm of chromosome 20. Sequence data analysis of potential candidate genes failed to detect any pathogenic variant. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. DNA of eight individuals including three affected subjects was used for homozygosity mapping. Genotyping was performed using the Affymetrix Axiom_GW_Hu_SNP array. Briefly, 250 ng genomic DNA was digested with Digestion Master Mix containing 2 µl NE buffer 2 (10X), 0.5 µl BSA (100X; 10 mg/ml) and 1 µl Nsp1. Digested DNA sample was ligated to Nsp1 adaptor using T4 DNA ligase and amplified by 2 µl of TITANIUM Taq DNA polymerase (50X) and 100 µM PCR primer. PCR products were purified on a Clean-Up plate (Clontech Lab, Madison, USA) and eluted by RB buffer. Purified PCR products were fragmented using Fragmentation Reagent (0.05U/µl DNase 1) for 35 minutes at 37°C followed by labeling of fragmented samples with Labeling Master Mix (30 mM GeneChip DNA Labeling Reagent, 30 U/µl Terminal Deoxynucleotidyl Transferase) for 4 hours at 37°C. Labeled samples were hybridized to Axiom_GW_Hu_SNP array by mixing the sample with Hybridization Master Mix, denatured on thermoblock and loaded on to Array. Array was then placed in a hybridization oven (GeneChip Hybridization Oven 640, USA) for 16-18 hours. After hybridization, array was washed and stained on an automated Fluidic Station 450 followed by scanning on GeneChip Scanner 3000 7G using GeneChip Operating Software (GCOS).
2014-03-20 | E-GEOD-56043 | biostudies-arrayexpress
Project description:Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone (FSH). Though POI affects many aspects of women’s health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch chain amino acid (BCAA) insufficiency related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57 B6 mice. A mechanism study revealed that the BCAA insufficiency induced POI is associated with abnormal activation of the ceramide-ROS axis and consequent impairment of ovarian granulosa cell function. Significantly, dietary supplement of BCAA prevented the development of ROS-induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.
2022-10-13 | PXD037353 |
Project description:Identify urinary exosome microRNAs that are unique to premature ovarian insufficiency
| PRJNA847205 | ENA
Project description:The aim of this study is to identify the expression profile of mRNA in granulosa cells of POI We performed gene expression profiling analysis using data obtained from RNA-seq of the GCs in 6 POI patients and 5 control patients.This study provides a better understanding of molecular mechanism of POI and identifies the possible biomarkers of POI.
2023-10-31 | GSE201276 | GEO
Project description:Primary ovarian insufficiency (POI) is a complex disorder that affects many genes and the underlying molecular mechanisms remain to be fully elucidated. In this study, a homozygous point mutation, c.808C>T, in the DAZL gene of a POI patient was identified. This homozygous variant causes a C-terminal truncation of DAZL and down-regulation of germ-line gene NANOS3 expression, among other dysregulated genes, in human primordial germ cells (hPGCs) in vitro. Mechanistically, we discovered that the truncated DAZL had defects in regulating mRNA translation for NANOS3, VASA, and SYCP3 - all essential for gametogenesis. Additionally, the truncated DAZL showed impaired interaction with Poly(A)-binding proteins (PABPs), a crucial component of the translation initiation complex. At the cellular level, the truncated mutation resulted in increased apoptosis of in vitro hPGCs. Our findings reveal that the c.808C>T mutation in DAZL causes dysregulated expressions of many genes, increases germ cell apoptosis and ultimately leads to POI.
2023-10-18 | GSE245155 | GEO
Project description:Premature ovarian insufficiency (POI) is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40. It represents a significant detriment to female fertility. However, the known POI-causative genes currently account for only a fraction of cases. To elucidate the genetic factors underlying POI, we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111. In a subsequent replication study involving 1030 POI patients, this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants. These variants collectively account for eight cases, representing 0.78% of the study cohort. A further study involving 500 patients with diminished ovarian reserves also identified two additional RNF111 variants. Notably, RNF111 encodes an E3-ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway. Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice, monkeys, and humans. To further investigate the functional implications of RNF111 variants, we generated two mouse models: one with a heterozygous missense mutation (Rnf111+/M) and another with a heterozygous null mutation (Rnf111+/−). Both mouse models exhibited impaired female fertility, characterized by reduced litter sizes and small ovarian reserve. Additionally, RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries. In conclusion, our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.
2024-06-11 | GSE252791 | GEO
Project description:Our study is designed to demonstrate altered profiles of lncRNAs in the granulosa cells from patients with bPOI. Functional studies will be further confirmed. This study will provide new viewpoint for understanding the roles of non-coding RNA for GCs function, as well as potential etiologic mechanism for POI.
2020-02-17 | GSE135697 | GEO
Project description:Women diagnosed with primary ovarian insufficiency (POI) cannot produce oocytes and therefore are not candidates for the majority of current assisted reproductive technology treatments. POI can in some cases arise due to errors in primordial germ cell (PGC) specification and PGC differentiation into oogonia and oocytes. To address the ability to reverse germ cell loss in infertile women through induced reprogramming followed by germ cell differentiation, we derived hiPSCs from monozygotic (MZ) twins discordant for POI. hiPSC lines derived from all research participants successfully differentiated into primordial germ cell-like cells (hPGCLCs), as determined by flow cytometry, immunofluorescence, and 10x single-cell RNA sequencing. Therefore, we demonstrate that after epigenetic reprogramming, infertile women with POI can re-specify germ cells. The research presented here advances efforts of fertility restoration and understanding of the germ cell lineage.
2022-10-20 | GSE181205 | GEO