Female Infertility: Primary Ovarian Insufficiency
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PROVIDER: PRJNA330891 | ENA |
REPOSITORIES: ENA
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Project description:<p>Premature ovarian failure, or primary ovarian insufficiency (POI) is a phenotype of diminished or absent ovarian function occurring in 1-2% of reproductive aged women. Most cases occur spontaneously. Evaluation of the gametes in women with POI is difficult and invasive. Practitioners must often rely on indirect biomarkers of ovarian function and oocyte health, making it difficult to identify patients who may benefit from therapies allowing them to achieve pregnancy utilizing their own oocytes. This study will generate exome sequences from POI patients in an effort to elucidate the causes of unexplained POI and to better understand the normal processes of ovarian aging. A better understanding of the genetics of ovarian function may lead to new non-invasive tools for managing women's reproductive health, and direct better use of existing biomarkers in diagnosis, screening and predicting clinical outcomes. </p>
| phs001174 | dbGaP
Project description:Female Infertility: Primary Ovarian Insufficiency
| PRJNA330892 | ENA
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:Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female to male sex conversion in adult mature zebrafish prior to or after 90 days post fertilization (dpf); however, primary sex determination was not affected in early juveniles of adamts9 KO at 35 dpf. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicle) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex in zebrafish, and loss of adamts9 in zebrafish leads to ovarian follicle arrest, female infertility, and sex conversion in late juveniles and mature adults.
2024-04-16 | GSE264143 | GEO
Project description:Primary ovarian insufficiency (POI) is an early decline in ovarian function that leads to infertility. Conventional treatments for chemotherapy-induced POI are unsatisfactory. Mesenchymal stem cells (MSCs) have emerged as a therapeutic option, but the impact of estrogen niche-respond MSC secretome on ovarian regeneration and circadian rhythm remains unknown. This study revealed that the secretome of ER+pcMSCs (conditioned medium [CM] and E2-CM, respectively) significantly reduced the CTX-induced defects in ovarian folliculogenesis and circadian rhythm. The CM/E2-CM also reduced granulosa cell apoptosis and rescued angiogenesis in POI ovarian tissues. E2-CM presented a better effect than the CM. Cytokine array analysis showed a significant increase in cytokine/growth factors associated with immunomodulation and angiogenesis (including angiogenin). Neutralizing angiogenin in the CM/E2-CM significantly decreased its ability to promote HUVEC tube formation in vitro. Importantly, the ER+pcMSC secretome restored the CTX-induced circadian rhythm defects, including the expression of both the genes and proteins associated with ovarian circadian clock (such as Rora, E4bp4, Rev-erbα, and Dbp) and the locomotor activity. Further exosomal miRNA analysis showed the involved miRNAs in targeting the genes associated with POI rescue (Pten and Pdcd4), Caspase-3, estrogen synthesis (Cyp19a1), and importantly the ovarian clock regulation (E4bp4, Rev-erbα and Rev-erbβ).
2024-10-23 | GSE247568 | 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:Primary ovarian insufficiency (POI) refers to the loss of ovarian function under the age of 40 and results in amenorrhea and infertility. Our previous studies have shown that transplantation of mesenchymal stem cells (MSCs) and MSC-derived exosomes in chemotherapy-induced POI mouse ovaries can reverse the POI and eventually achieve pregnancy. Based on our recent studies, MSC-derived exosomes have almost equal therapeutic potentials as transplanted MSCs. However, it is still unclear whether exosomes can completely replace MSCs in POI treatment. In this study, we induced POI in C57/BL6 mice by chemotherapy (CXT) using a standard protocol. We compared the RNA expression pattern in ovarian tissue after MSC or exosome treatment. our data suggest that a minimal 10-fold increase, and ideally 100-fold increase, in the exosome concentration is required to generate more analogous results to MSC treatment.
2023-05-30 | GSE233743 | 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: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:Specification of the Germline in Monozygotic Twins with Discordant Primary Ovarian Insufficiency
| PRJNA751051 | ENA