Similar Datasets
Project description:The ovulatory LH surge induces rapid changes of transcriptome and cellular functions in granulosa cells (GCs) undergoing luteinization. However, it remains unclear how the changes in genome-wide gene expression are regulated. The changes of trimethylation of lysine 4 on histone H3 (H3K4me3) is associated with the rapid alteration of gene expression. In this study, we genome-widely investigated the changes of transcriptome and H3K4me3 status in mouse GCs undergoing luteinization during ovulation. GCs were obtained from mice treated with equine chorionic gonadotropin (eCG) before, 4 h and 12 h after human (h)CG injection. RNA-sequence identified a number of up- or down-regulated genes, which can be classified into six patterns according to the time-course changes of gene expression. A number of genes showed a transient up- or down-regulation at 4 h after hCG stimulation. Gene ontology analysis revealed that they were involved in the regulation of steroidogenesis, ovulation, COC expansion, angiogenesis, immune system, ROS metabolism, inflammatory response, and metabolisms. The newly identified cellular functions, DNA repair, autophagy and cell growth were found to be activated during ovulation. ChIP-sequence revealed a genome-wide and rapid change of H3K4me3 during ovulation. Integration of transcriptome and H3K4me3 data identified a number of H3K4me3-regulated genes, which were involved in the regulation of a lot of cellular functions for ovulation and luteinization. The present study demonstrated that genome-wide changes of H3K4me3 might contribute to the rapid change of genome-wide gene expression, which enables GCs acquire a lot of cellular functions within a short time for ovulation and luteinization.
2022-07-21 | GSE167938 | GEO
Project description:The ovulatory LH surge induces rapid changes of transcriptome and cellular functions in granulosa cells (GCs) undergoing luteinization. However, it remains unclear how the changes in genome-wide gene expression are regulated. The changes of trimethylation of lysine 4 on histone H3 (H3K4me3) is associated with the rapid alteration of gene expression. In this study, we genome-widely investigated the changes of transcriptome and H3K4me3 status in mouse GCs undergoing luteinization during ovulation. GCs were obtained from mice treated with equine chorionic gonadotropin (eCG) before, 4 h and 12 h after human (h)CG injection. RNA-sequence identified a number of up- or down-regulated genes, which can be classified into six patterns according to the time-course changes of gene expression. A number of genes showed a transient up- or down-regulation at 4 h after hCG stimulation. Gene ontology analysis revealed that they were involved in the regulation of steroidogenesis, ovulation, COC expansion, angiogenesis, immune system, ROS metabolism, inflammatory response, and metabolisms. The newly identified cellular functions, DNA repair, autophagy and cell growth were found to be activated during ovulation. ChIP-sequence revealed a genome-wide and rapid change of H3K4me3 during ovulation. Integration of transcriptome and H3K4me3 data identified a number of H3K4me3-regulated genes, which were involved in the regulation of a lot of cellular functions for ovulation and luteinization. The present study demonstrated that genome-wide changes of H3K4me3 might contribute to the rapid change of genome-wide gene expression, which enables GCs acquire a lot of cellular functions within a short time for ovulation and luteinization.
2022-07-21 | GSE167939 | GEO
Project description:Integrated analysis of transcriptome and histone modifications in granulosa cells during ovulation in female mice
| PRJNA705614 | ENA
Project description:Integrated analysis of transcriptome and histone modifications in granulosa cells during ovulation in female mice [ChIP-seq]
| PRJNA705643 | ENA
Project description:Integrated analysis of transcriptome and histone modifications in granulosa cells during ovulation in female mice [RNA-seq]
| PRJNA705644 | ENA
Project description:The ovulatory LH-surge increases Vegf gene expression in granulosa cells (GCs) undergoing luteinization during ovulation. To understand the factors involved in this increase, we examined the roles of two transcription factors and epigenetic mechanisms in rat GCs. GCs were obtained from rats treated with eCG before, 4?h, 8?h, 12?h and 24?h after hCG injection. Vegf mRNA levels gradually increased after hCG injection and reached a peak at 12?h. To investigate the mechanism by which Vegf is up-regulated after hCG injection, we focused on C/EBP? and HIF1?. Their protein expression levels were increased at 12?h. The binding activity of C/EBP? to the Vegf promoter region increased after hCG injection whereas that of HIF1? did not at this time point. The C/EBP? binding site had transcriptional activities whereas the HIF1? binding sites did not have transcriptional activities under cAMP stimulation. The levels of H3K9me3 and H3K27me3, which are transcriptional repression markers, decreased in the C/EBP? binding region after hCG injection. The chromatin structure of this region becomes looser after hCG injection. These results show that C/EBP? regulates Vegf gene expression with changes in histone modifications and chromatin structure of the promoter region in GCs undergoing luteinization during ovulation.
| S-EPMC6345775 | biostudies-literature
Project description:Recent studies have demonstrated an essential role for insulin signaling in folliculogenesis as conditional ablation of Igf1r in primary follicles elicits defective follicle-stimulating hormone responsiveness blocking development at the preantral stage. Thus the potential role of insulin action in the periovulatory window and in the corpus luteum is unknown. To examine this, we generated conditional Insr,Igf1r, and double receptor knockout mice driven by Pgr-Cre. These models escape the preantral follicle block and in response to superovulatory gonadotropins exhibit normal distribution of ovarian follicles and corpora lutea. However, single ablation of Igf1r leads to subfertility and mice lacking both receptors are infertile. Double knockout mice have impaired oocyte development and ovulation. While some oocytes are released and fertilized, subsequent embryo development is retarded, and the embryos potentially fail to thrive due to lack of luteal support. In support of this, we found reduced expression of key enzymes in the steroid synthesis pathway and reduced serum progesterone. In addition to metabolic and steroidogenic pathways, RNA-sequencing analysis revealed transcription factor-3 as an important transcription factor downstream of insulin signaling. Collectively, these results highlight the importance of growth factors of the insulin family during two distinct windows of follicular development, ovulation, and luteinization.
| S-EPMC7781071 | biostudies-literature
Project description:It has been known that EGF-like factor secreted from LH-stimulated granuloma cells acts on granulosa cells and cumulus cells to induce ovulation process. Granulosa cells are changed the morphology with differentiating cell functions to produce progesterone. Cumulus cells are detached to make a space between the cells to accumulate hyaluronan rich matrix. LH also changes extracellular matrix (ECM) components including fibronectin in the follicular walls and granulosa cell layers. EGF like factor and fibronectin synergistically play important roles in numerous cell functions, especially cancer cell migration, estimating that fibronectin would impact on granulosa cells and cumulus cells. To clear this hypothesis, the localizations of fibronectin and its receptor integrin were observed by immunofluorescence technique. The functions were monitored by the detection of downstream signaling pathway, focal adhesion kinase (FAK). The pharmacological approach in both in vivo and in vitro were used for analyzing the physiological roles of FAK during ovulation process. The immunofluorescence staining revealed that fibronectin and integrin were observed in granulosa cells, cumulus cells and the space between cumulus cells and oocyte at 4 and 8 h after hCG injection. Concomitantly with the changes of fibronectin-integrin localization, FAK was phosphorylated in periovulatory follicles. The injection of FAK inhibitor suppressed not only ovulation but also luteinization of granulosa cells and cumulus expansion. In cultured-granulosa cells, fibronectin-integrin synergistically activated FAK with amphiregulin (AREG). Such cooperative stimulations induced a morphological change in granulosa cells, which resulted in the maximum level of progesterone production via the induction of Hsd3b. When cumulus-oocyte complexes (COCs) were cultured with AREG in the presence of serum, the maximum level of cumulus expansion was observed. The AREG-induced cumulus expansion was also suppressed by FAK inhibitor. Thus, it is concluded that fibronectin and AREG synergistically activate FAK not only in granulosa cells and cumulus cells to induce successful ovulation process.
| S-EPMC5805282 | biostudies-literature
Project description:Histone methylation is one of the most widely studied post-transcriptional modifications. It is thought to be an important epigenetic event that is closely associated with cell fate determination and differentiation. To explore the spatiotemporal expression of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3) epigenetic marks and methylation or demethylation transferases in tooth organ development, we measured the expression of SET7, EZH2, KDM5B and JMJD3 via immunohistochemistry and quantitative polymerase chain reaction (qPCR) analysis in the first molar of BALB/c mice embryos at E13.5, E15.5, E17.5, P0 and P3, respectively. We also measured the expression of H3K4me3 and H3K27me3 with immunofluorescence staining. During murine tooth germ development, methylation or demethylation transferases were expressed in a spatial-temporal manner. The bivalent modification characterized by H3K4me3 and H3K27me3 can be found during the tooth germ development, as shown by immunofluorescence. The expression of SET7, EZH2 as methylation transferases and KDM5B and JMJD3 as demethylation transferases indicated accordingly with the expression of H3K4me3 and H3K27me3 respectively to some extent. The bivalent histone may play a critical role in tooth organ development via the regulation of cell differentiation.
| S-EPMC5153591 | biostudies-literature
Project description:Adenosine deaminases acting on RNA-(ADAR) comprise one family of RNA editing enzymes that specifically catalyze adenosine to inosine (A-to-I) editing. A granulosa cell (GC) specific Adar depleted mouse model [Adar flox/flox:Cyp19a1-Cre/+ (gcAdarKO)] was used to evaluate the role of ADAR1 during the periovulatory period. Loss of Adar in GCs led to failure to ovulate at 16 h post-hCG, delayed oocyte germinal vesicle breakdown and severe infertility. RNAseq analysis of GC collected from gcAdarKO and littermate control mice at 0 and 4 h post-hCG following a super-ovulatory dose of eCG (48 h), revealed minimal differences after eCG treatment alone (0 h), consistent with normal folliculogenesis observed histologically and uterine estrogenic responses. In contrast, 300 differential expressed genes (DEGs; >1.5-fold change and FDRP < 0.1) were altered at 4 h post-hCG. Ingenuity pathway analysis identified many downstream targets of estrogen and progesterone pathways, while multiple genes involved in inflammatory responses were upregulated in the gcAdarKO GCs. Temporal expression analysis of GCs at 0, 4, 8, and 12 h post-hCG of Ifi44, Ifit1, Ifit3b, and Oas1g and Ovgp1 confirmed upregulation of these inflammatory and interferon genes and downregulation of Ovgp1 a glycoprotein involved in oocyte zona pellucida stability. Thus, loss of ADAR1 in GCs leads to increased expression of inflammatory and interferon response genes which are temporally linked to ovulation failure, alterations in oocyte developmental progression and infertility.
| S-EPMC9695778 | biostudies-literature