LH/hCG regulation of circular RNA in mural granulosa cells during the periovulatory period in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE239510 | GEO | 2023/07/28
REPOSITORIES: GEO
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Project description:Ovarian follicles undergo a series of dynamic changes following the ovulatory surge of luteinizing hormone including cumulus expansion, oocyte maturation, ovulation, and luteinization. Post-transcriptional gene regulatory events are critical for mediating LH follicular responses, and among all RNA isoforms, circular RNA (circRNA) is one of the most abundant forms present in cells, yet they remain the least studied. Functionally, circRNA can act as miRNA sponges, protein sponges/decoys, and regulators of transcription and translation. In the context of ovarian follicular development, the identity and roles of circRNA are relatively unknown. In the present study, high throughput RNA sequencing of granulosa cells immediately prior to and 4-h after the LH/hCG surge identified 42,381 circRNA originating from 7712 genes. A total of 54 circRNA were identified as differentially expressed between 0-h and 4-h time points (Fold Change ± 1.5, FDR ≤ 0.1), among them 42 circRNA were upregulated and 12 circRNA were downregulated. All differentially expressed circRNA between the 0-h and 4-h groups were subjected to circinteractome analysis and identified networks of circRNA-protein and circRNA-miRNA were further subjected to "micro-RNA target filter analysis" in Ingenuity Pathway Analyses, which resulted in the identification of miRNA targeted mRNAs. A comparison of these circRNA target mRNAs with LH-induced mRNAs identified Runx2, Egfr, Areg, Sult1el, Cyp19a1, Cyp11a1, and Hsd17b1 as targets of circKif2, circVcan, circMast4, and circMIIt10. These newly identified LH/hCG-induced circRNA, their target miRNA and protein networks provide new insights into the complex interactions associated with periovulatory follicular development.
| S-EPMC10488058 | biostudies-literature
Project description:LH/hCG regulation of circular RNA in mural granulosa cells during the periovulatory period in mice
| PRJNA999617 | ENA
Project description:The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. However, the post-transcriptional gene expression studies on miRNA level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Libraries of all 6 samples were sequenced twice, generating 2 technical replicates for each sample. Differential gene expression study was performed on the pooled results of technical replicates.
2013-08-05 | E-GEOD-46489 | biostudies-arrayexpress
Project description:The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. The current study determined the mRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Differential gene expression study was performed. The identified gene expression profile was also used for predicting targets for miRNAs that were also identified from the same samples (GSE46489).
2013-08-05 | E-GEOD-46490 | biostudies-arrayexpress
Project description:The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. However, the post-transcriptional gene expression studies on miRNA level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization.
2013-08-05 | GSE46489 | GEO
Project description:The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. The current study determined the mRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization.
2013-08-05 | GSE46490 | GEO
Project description:MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3' untranslated region of messenger RNAs to either inhibit or enhance translation. The extent and hormonal regulation of miRNA expression by ovarian granulosa cells and their role in ovulation and luteinization is unknown. In the present study, miRNA array analysis was used to identify 212 mature miRNAs as expressed and 13 as differentially expressed in periovulatory granulosa cells collected before and after an ovulatory dose of hCG. Two miRNAs, Mirn132 and Mirn212 (also known as miR-132 and miR-212), were found to be highly upregulated following LH/hCG induction and were further analyzed. In vivo and in vitro temporal expression analysis by quantitative RT-PCR confirmed that LH/hCG and cAMP, respectively, increased transcription of the precursor transcript as well as the mature miRNAs. Locked nucleic acid oligonucleotides complementary to Mirn132 and Mirn212 were shown to block cAMP-mediated mature miRNA expression and function. Computational analyses indicated that 77 putative mRNA targets of Mirn132 and Mirn212 were expressed in ovarian granulosa cells. Furthermore, upon knockdown of Mirn132 and Mirn212, a known target of Mirn132, C-terminal binding protein 1, showed decreased protein levels but no change in mRNA levels. The following studies are the first to describe the extent of miRNA expression within ovarian granulosa cells and the first to demonstrate that LH/hCG regulates the expression of select miRNAs, which affect posttranscriptional gene regulation within these cells.
| S-EPMC2780477 | biostudies-literature
Project description:The LH surge induces panoply of events that are essential for ovulation and corpus luteum formation. The transcriptional responses to the LH surge of pre-ovulatory granulosa cells are complex and still poorly understood. In the present study, a genome wide bovine oligo array was used to determine how the gene expression profiles of granulosa cells are modulated by the LH surge. Granulosa cells from three different statuses were used (1) 2 h before the induction of the LH surge, (2) 6 h and (3) 22 h after the LH surge to assess the short and long term effects of this hormone on follicle differentiation. The results obtained were a list of differentially expressed transcripts for each granulosa cell group. To provide a comprehensive understanding of the processes at play, biological annotations were used to reveal the different functions of transcripts, confirming that the LH surge acts in a temporal manner. The pre-LH group is involved in typical tasks such as cell division, development and proliferation, while the short response of the LH surge included features such as response to stimulus, vascularisation and lipid synthesis, which are indicative of cells preparing for ovulation. The late response of granulosa cells revealed terms associated with protein localization and intra-cellular transport corresponding to the future secretion task that will be required for the transformation of granulosa cells into corpus luteum. Overall, results described in this study provide new insights into the different transcriptional steps that granulosa cells go through during ovulation and before luteinization. Three biological granulosa cells samples: 2 h pre-LH vs. 6 h post-LH vs. 22 h post-LH. Biological replicates: 3 with a technical dye-swap replicates (Dy 547 and Dy 647) for each biological replicate. Hybridizations were performed in a loop design for a total a 9 hybridizations.
2010-10-15 | E-GEOD-23900 | biostudies-arrayexpress
Project description:Inhibin α knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells. (2) Genotypes (WT, Inh KO) collected from 2 preovulatory granulosa cells with and without hCG, in triplicate independent samples
2011-02-01 | E-GEOD-20466 | biostudies-arrayexpress
Project description:The LH surge induces panoply of events that are essential for ovulation and corpus luteum formation. The transcriptional responses to the LH surge of pre-ovulatory granulosa cells are complex and still poorly understood. In the present study, a genome wide bovine oligo array was used to determine how the gene expression profiles of granulosa cells are modulated by the LH surge. Granulosa cells from three different statuses were used (1) 2 h before the induction of the LH surge, (2) 6 h and (3) 22 h after the LH surge to assess the short and long term effects of this hormone on follicle differentiation. The results obtained were a list of differentially expressed transcripts for each granulosa cell group. To provide a comprehensive understanding of the processes at play, biological annotations were used to reveal the different functions of transcripts, confirming that the LH surge acts in a temporal manner. The pre-LH group is involved in typical tasks such as cell division, development and proliferation, while the short response of the LH surge included features such as response to stimulus, vascularisation and lipid synthesis, which are indicative of cells preparing for ovulation. The late response of granulosa cells revealed terms associated with protein localization and intra-cellular transport corresponding to the future secretion task that will be required for the transformation of granulosa cells into corpus luteum. Overall, results described in this study provide new insights into the different transcriptional steps that granulosa cells go through during ovulation and before luteinization.
2010-10-15 | GSE23900 | GEO