YTHDF2 mediates the action of BDNF stimulating proliferation of porcine follicle granulosa cells
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PROVIDER: PRJNA1039737 | ENA |
REPOSITORIES: ENA
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Project description:Total RNA of porcine follicle granulosa cells from different groups was extracted and RNA purity and quality control were performed.
2023-11-30 | GSE247561 | GEO
Project description:FSH is considered as the most critical regulatory factor for follicle growth and development. It is widely acknowledged that exogenous administration of FSH can effectively stimulate ovulation.However, these techniques have several drawbacks such as high cost and detrimental effects on hormone balance and embryo implantation.Sulforaphane (SFN) is a naturally occurring compound that belongs to the isothiocyanate group, which is predominant in cruciferous vegetables.Our previous research demonstrated SFN could inhibit hypoxia-evoked apoptosis in porcine GCs. Intriguingly, SFN exhibits a biphasic dose-response, stimulating cell growth at low doses in various mammalian cells. Therefore,to investigate the functional implications of sulforaphane in the regulation of granulosa cell proliferation, we conducted a gene expression profiling analysis using RNA-seq data, comparing SFN to follicle stimulating hormone (FSH).
2024-10-01 | GSE233365 | GEO
Project description:PKA activation by FSH is essential to transduce FSH-mediated effects on granulosa cell proliferation, differentiation and steroidogenesis. However, It is unknown whether activation of PKA is sufficient to account for the entire program of granulosa cell responses to FSH. We addressed this question by conducting a comprehensive comparative analysis of signaling pathways and gene expression profiles of granulosa cells stimulated with FSH or expressing a constitutively active PKA mutant, PKA-CQR.
2016-10-01 | GSE73955 | GEO
Project description:BackgroundWomen with anovulatory polycystic ovary syndrome (PCOS) are generally insulin-resistant and as a consequence are often treated with the biguanide metformin. Results with metformin have, however, been variable with some studies demonstrating induction of regular cycles and an increase in ovulation, whereas others do not. Hence more understanding is needed regarding the mechanism of metformin's actions in ovarian granulosa cells especially in light of previous demonstrations of direct actions.ObjectiveThe aim of this study was to investigate metformin's interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary.MethodsThe effect of metformin on FSH and forskolin-stimulated aromatase expression in human granulosa cells was measured by quantitative real-time PCR. Activity was assessed after transfection with a promoter II-luciferase construct, and by an RIA measuring conversion of androgen to estrogens. The effect on FSH receptor (FSHR) mRNA was assessed by quantitative PCR. Levels of phosphorylated cAMP response element binding protein (CREB) and CREB-regulated transcription coactivator 2 (CRTC2) were measured by Western blotting and cAMP by a bioluminescent assay.ResultsMetformin markedly reduced FSH but not forskolin-stimulated aromatase expression and activity. This effect was exerted by inhibition of basal and ligand-induced up-regulation of FSHR expression. Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene. This is mediated in an AMP-activated protein kinase-independent manner, and does not involve alteration of cAMP levels.ConclusionThese finding have implications for the use of metformin in the treatment of anovulation in women with PCOS.
| S-EPMC3784648 | biostudies-literature
Project description:Gene expression analysis of porcine granulosa cells treated in virtro with sulforaphane or follicle stimulating hormone
| PRJNA975908 | ENA
Project description:Purpose of reviewTo review the current knowledge of genetic variants in the two genes affecting the individual responsiveness to follicle-stimulating hormone (FSH) action-the FSH beta-subunit (FSHB) and the FSH receptor (FSHR), as well as the pharmacogenetic ramifications of the findings.Recent findingsFour common variants in the FSHB and the FSHR genes were shown to exhibit significant effect on FSH action: linked FSHR variants Thr307Ala and Asn680Ser determining common receptor isoforms, and gene expression affecting polymorphisms FSHR -29G/A and FSHB -211G/T. In women, the FSHR Thr307Ala/Asn680Ser polymorphisms show consistent predictive value for estimating the most optimal recombinant FSH dosage in controlled ovarian hyperstimulation (COH). The same variants exhibit a potential for the pharmacogenetic assessment of the treatment of polycystic ovarian syndrome. The FSHR -29G/A variant was also shown to contribute to ovarian response to COH. Pilot studies have suggested the FSHB -211 TT homozygous oligozoospermic men with genetically determined low concentration of FSH, as potentially the best responders to FSH treatment; furthermore, modulation of this response by FSHR polymorphisms is possible.SummaryGenetic variants in FSHB and FSHR exhibit a potential for pharmacogenetic applications in selecting appropriate treatment options (timing and dosage) in male and female conditions requiring or benefiting from FSH therapy.
| S-EPMC3348539 | biostudies-literature
Project description:CCR4-NOT deadenylase is a major regulator of mRNA turnover in eukaryotes. It contains 2 heterogeneous catalytic subunits encoded by Cnot7/8 and Cnot6/6l genes in vertebrates, respectively. The physiological function of each catalytic subunit was unclear due to potential gene redundancy in vivo. In this study Cnot6/6l double knockout mice were generated. These mice were viable and generally healthy, but females were infertile with irregular estrus cycle and poor ovarian responses to gonadotropins. Follicle-stimulating hormone (FSH) stimulated transcription and translation of mRNAs encoding CNOT6 and CNOT6L in ovarian granulosa cells through the activity of phosphoinositide 3-kinase signaling pathway. Results of transcriptome analyses indicated that FSH downregulated a large number of transcripts in granulosa cells during the transition from pre-antral to antral follicles in a CNOT6/6L-dependent manner. These two deadenylases functioned as key effectors of FSH in altering the developmental programs in granulosa cells and triggered clearance of specific transcripts in growing follicles, particularly those encoding repressing factors of granulosa cell proliferation and steroidogenesis. These results demonstrated that FSH modulates granulosa cells function by stimulating selective translational activation and degradation of existed mRNAs, in additional to inducing de novo gene transcription. Meanwhile, this study provides in vivo evidence that CCR4-NOTCNOT6/6L-mediated mRNA deadenylation is dispensable in most somatic cell types, but is essential for the female reproductive endocrine regulation.
2021-11-04 | GSE158773 | GEO
Project description:To study the role of the protein YTHDF2 during female gametogenesis, its gene was conditionally deleted in oocytes. Total RNA samples from YTHDF2 deficient GV and MII oocytes (and control oocytes) were subjected to array profiling.
2018-02-12 | E-MTAB-5576 | biostudies-arrayexpress
Project description:The FSH microarray was performed to identify new genes to be regulated by FSH in granulosa cells, in order to ultimately find genes potentially important in oocyte maturation and development.
2010-03-31 | E-MEXP-1763 | biostudies-arrayexpress
Project description:Using recombinant DNA technologies, a new chimeric gene containing the coding sequences of the follicle stimulating hormone (FSH) β-subunit and the C-terminal peptide of the human chorionic gonadotrophin (hCG) β-subunit have been designed to generate a new gonadotrophin named corifollitrophin alfa. Corifollitrophin alfa has longer elimination half-life and a slower rate of absorption compared with FSH, which makes corifollitrophin alfa a long-acting hormone employed as a substitute of the recombinant FSH (recFSH) in the controlled ovarian stimulation (COS). The purpose of this study is to compare the gene expression profiles elicited by bioequivalent doses of corifollitrophin alfa or recFSH in primary cultures of human granulosa cells (hGCs). Both gonadotrophins exert their functions by binding FSH receptors (FSHRs), activating signaling pathways that increase the cyclic adenosine monophosphate (cAMP) intracellular content. Bioequivalence has been defined as the dose/duration of gonadotrophin treatment able to promote the same amount of intracellular cAMP. Primary cultured hGCs were treated with different doses of either gonadotrophin and the cAMP was measured after different incubation times to establish the bioequivalence. Results obtained by comparing the bioequivalent treatments, showed that corifollitrophin alfa is more effective than recFSH in inducing aromatase gene expression after 6 and 24 hours from the initial stimulation in agreement with its long-acting characteristic’s.
2020-06-01 | GSE115846 | GEO