Analysis of Bone Morphogenetic Protein 15 (BMP15)-induced transcriptome in human granulosa cells for the identification of novel candidate genes for Primary Ovarian Insufficiency
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PROVIDER: PRJNA738453 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of primary cultures of human granulosa cells (hGCs) stimulated with recombinant human BMP15 (rhBMP15) at gene expression level. The hypothesis tested in the present study was that rhBMP15 regulates genes and processes of maturation and differenti
2021-06-17 | GSE178302 | GEO
Project description:Granulosa cells abnormalities are one of the characteristics of premature ovarian insufficiency (POI). Abnormal expression of serine/arginine-rich splicing factor 1 (SRSF1) can causes a variety of diseases, but the role of SRSF1 in mouse granulosa cells has been poorly reported. In this study, we found that SRSF1 was expressed in the nuclei of both mouse oocytes and granulosa cells. Specific knockout of SRSF1 in granulosa cells was performed using Foxl2-creERT2 mice, and morphological staining showed that follicular development was blocked. In addition, granulosa cell proliferation decreased and cell apoptosis increased. The differential gene Gene Ontology (GO) analysis of RNA-Seq results showed abnormal expression of DNA repair, cell killing and other signaling pathways. Alternative splicing (AS) analysis showed that SRSF1 affected DNA damage in granulosa cells by regulating genes related to DNA repair. In conclusion, SRSF1 in granulosa cells affects female reproduction by controlling the development of follicles through regulating granulosa cell DNA repair related genes.
2024-01-01 | GSE228975 | GEO
Project description:BackgroundBone morphogenetic protein 15 (BMP15) is expressed in oocytes and plays a crucial role in the reproduction of mono-ovulating species. In humans, BMP15 gene mutations lead to imperfect protein function and premature ovarian insufficiency. Here we investigated the BMP15 gene variants in a population of Iranian women with premature ovarian insufficiency. We conducted predictive bioinformatics analysis to further study the outcomes of BMP15 gene alterations.MethodsTwenty-four well-diagnosed premature ovarian insufficiency cases with normal karyotype participated in this study. The entire coding sequence and exon-intron junctions of the BMP15 gene were analyzed by direct sequencing. In-silico analysis was applied using various pipelines integrated into the Ensembl Variant Effect Predictor online tool. The clinical interpretation was performed based on the approved guidelines.ResultsBy gene screening of BMP15, we discovered p.N103K, p.A180T, and p.M184T heterozygous variants in 3 unrelated patients. The p.N103K and p.M184T were not annotated on gnomAD, 1000 Genome and/or dbSNP. These mutations were not identified in 800 Iranians whole-exome sequencing that is recorded on Iranom database. We identified the p.N103K variant in a patient with secondary amenorrhea at the age of 17, elevated FSH and atrophic ovaries. The p.M184T was detected in a sporadic case with atrophic ovaries and very high FSH who developed secondary amenorrhea at the age of 31.ConclusionsHere we newly identified p.N103K and p.M184T mutation in the BMP15 gene associated with idiopathic premature ovarian insufficiency. Both mutations have occurred in the prodomain region of protein. Despite prodomain cleavage through dimerization, it is actively involved in the mature protein function. Further studies elucidating the roles of prodomain would lead to a better understanding of the disease pathogenesis.
| S-EPMC8886931 | biostudies-literature
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:WNT4 is required for normal ovarian follicle development and female fertility in mice, but how its signal is transduced remains unknown. Fzd1 encodes a WNT receptor whose expression is markedly induced in both mural granulosa cells and cumulus cells during the preovulatory period, in a manner similar to Wnt4. To study the physiological roles of FZD1 in ovarian physiology and to determine if it serves as receptor for WNT4, Fzd1-null mice were created by gene targeting. Whereas rare Fzd1-/- females were sterile due to uterine fibrosis and ovarian tubulostromal hyperplasia, the majority were subfertile, producing M-bM-^IM-^H1 less pup per litter on average relative to controls. Unlike WNT4-deficient mice, ovaries from Fzd1-/- mice had normal weights, numbers of follicles, steroid hormone production and WNT4 target gene expression levels. Microarray analyses of granulosa cells from periovulatory follicles revealed few genes whose expression was altered in Fzd1-/- mice. However, gene expression analyses of cumulus-oocyte complexes (COCs) revealed a blunted response of both oocyte (Zp3, Dppa3, Nlrp5, Bmp15) and cumulus (Btc, Ptgs2, Sema3a, Ptx3, Il6, Nts, Alcam, Cspg2) genes to the ovulatory signal, whereas the expression of these genes was not altered in WNT4-deficient COCs from Wnt4tm1.1Boer/tm1.1Boer;Tg(CYP19A1-cre)1Jri mice. Despite altered gene expression, cumulus expansion appeared normal in Fzd1-/- COCs both in vitro and in vivo. Together, these results indicate that Fzd1 is required for normal female fertility and may act in part to regulate oocyte maturation and cumulus cell function, but is unlikely to function as the sole ovarian WNT4 receptor. Triplicate RNA samples from granulosa cells of Fzd1 KO mice are compared to triplicate RNA samples from granulosa cells of control Fzd1 WT mice
2012-09-01 | E-GEOD-38315 | biostudies-arrayexpress
Project description:The lipid metabolism of granulosa cells plays a pivotal role in the development of goose follicles. However, the mechanisms by which lipid droplet-associated proteins regulate lipid droplets and influence cellular lipid metabolism remain poorly understood. To address this, our study systematically identified lipid droplet-associated proteins in goose follicular granulosa cells and analyzed these proteins at five distinct time points, in both pre-hierarchical granulosa cells and hierarchical granulosa cells, thereby obtaining relevant information on lipid droplet-associated proteins.
2025-03-26 | PXD061272 | Pride
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:mRNA expression profiling in human granulosa cell tumor cell line and normal granulosa cells
2012-01-26 | E-MTAB-957 | biostudies-arrayexpress
Project description:Although the existence of a regulatory paracrine feedback system between oocytes and follicular somatic cells has been postulated for some time, there has not yet been any definitive evidence that such a communication system exists. Herein we present a previously undescribed oocyte-granulosa cell (GC) feedback communication system involving an oocyte-derived factor, bone morphogenetic protein-15 (BMP-15) and a GC-derived factor, kit ligand (KL), both of which have been shown to be crucial regulators of female reproduction. We used a coculture system of rat oocytes and GCs and found that BMP-15 stimulates KL expression in GCs, whereas KL inhibits BMP-15 expression in oocytes, thus forming a negative feedback loop. Moreover, KL, like BMP-15, exhibited mitotic activity on GCs in the presence of oocytes. Because c-kit (KL receptor) is expressed in oocytes but not GCs, the oocytes must be involved in mediating the KL-induced GC mitosis. Furthermore, the blockage of c-kit signaling in oocytes by using a c-kit neutralizing antibody markedly suppressed BMP-15-induced GC mitosis, suggesting that the oocyte must play a role in the GC responses to BMP-15. In contrast, the c-kit antibody had no effect on the mitotic activities of two other known GC mitogens, activin-A and BMP-7. Altogether, this study presents direct evidence of a negative feedback system governed by oocyte-derived BMP-15 and GC-derived KL, and demonstrates that the mitotic activities of BMP-15 and KL for GCs depend on this oocyte-GC communication system. We hypothesize that the negative feedback system most likely plays a pivotal role in early folliculogenesis.
| S-EPMC123020 | biostudies-literature