Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA98279 | ENA |
REPOSITORIES: ENA
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Project description:Mouse oocytes control cumulus cell metabolic processes that are deficient in the oocytes themselves and this delegation is necessary for oocyte development. Oocyte-derived bone morphogenetic factor 15 (BMP15) and growth differentiation factor 9 (GDF9) appear to be key regulators of follicular development. The effect of these factors on cumulus cell function before the preovulatory surge of luteinizing hormone (LH) was assessed by analysis of the transcriptomes of cumulus cells from wildtype (WT), Bmp15-/-, and Bmp15-/- Gdf9+/- double mutant (DM) mice using microarray analysis. The biological themes associated with the most highly-affected transcripts were identified using bioinformatic approaches, IPA and GenMAPP/MAPPFinder. There were 5,332, 7,640, and 2,651 transcripts identified to be significantly changed in the comparisons of Bmp15-/- vs. WT, DM vs. WT, and DM vs. Bmp15-/- respectively by the criteria of FC (fold change) p <0.01. Among theses changed transcripts, 744 were commonly changed in all three pair-wise comparisons, and hence were considered to be the most highly affected transcripts by mutation of Bmp15 and Gdf9. IPA Analyses revealed that metabolism was the major theme associated with the most highly-changed transcripts: glycolysis and sterol biosynthesis were the two most significantly affected pathways. Most of the transcripts encoding enzymes for sterol biosynthesis were down-regulated in both mutant cumulus cells and in WT cumulus cell after oocytectomy. Similarly, there was a reduction of de novo-synthesized cholesterol in these cumulus cells. This suggests that oocytes regulate cumulus cell metabolism, particularly sterol biosynthesis, by promoting the expression of corresponding transcripts. Furthermore, in WT-mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol, and Ebp, which encode enzymes in the sterol biosynthetic pathway, were found to be expressed robustly in cumulus cells, but expression was barely detectable in oocytes. Levels of de novo-synthesized cholesterol were significantly higher in cumulusâenclosed oocytes than denuded oocytes. These results indicate that mouse oocytes are deficient in their ability to synthesize cholesterol and require cumulus cells to provide them with products of the sterol biosynthetic pathway. Oocyte-derived BMP15 and GDF9 may promote this metabolic pathway in cumulus cells as compensation for their own deficiencies. Experiment Overall Design: Three sets of independent cumulus cell samples were collected for each genotype (wild type, Bmp15-/-, and Bmp15-/-Gdf9+/-) of mice, and were used for the array study as shown below. Experiment Overall Design: Array Genotype Sample Experiment Overall Design: GC_430_2_GES05_0161_033105_1.CEL WT 1 Experiment Overall Design: GC_430_2_GES05_0162_033105_1.CEL WT 2 Experiment Overall Design: GC_430_2_GES05_0163_033105_1.CEL WT 3 Experiment Overall Design: GC_430_2_GES05_0164_033105_1.CEL Bmp15-/- 4 Experiment Overall Design: GC_430_2_GES05_0165_033105_1.CEL Bmp15-/- 5 Experiment Overall Design: GC_430_2_GES05_0166_033105_1.CEL Bmp15-/- 6 Experiment Overall Design: GC_430_2_GES05_0167_033105_1.CEL DM 7 Experiment Overall Design: GC_430_2_GES05_0168_033105_1.CEL DM 8 Experiment Overall Design: GC_430_2_GES05_0169_033105_1.CEL DM 9
2008-06-15 | E-GEOD-7225 | biostudies-arrayexpress
Project description:Mouse oocytes control cumulus cell metabolic processes that are deficient in the oocytes themselves and this delegation is necessary for oocyte development. Oocyte-derived bone morphogenetic factor 15 (BMP15) and growth differentiation factor 9 (GDF9) appear to be key regulators of follicular development. The effect of these factors on cumulus cell function before the preovulatory surge of luteinizing hormone (LH) was assessed by analysis of the transcriptomes of cumulus cells from wildtype (WT), Bmp15-/-, and Bmp15-/- Gdf9+/- double mutant (DM) mice using microarray analysis. The biological themes associated with the most highly-affected transcripts were identified using bioinformatic approaches, IPA and GenMAPP/MAPPFinder. There were 5,332, 7,640, and 2,651 transcripts identified to be significantly changed in the comparisons of Bmp15-/- vs. WT, DM vs. WT, and DM vs. Bmp15-/- respectively by the criteria of FC (fold change) p <0.01. Among theses changed transcripts, 744 were commonly changed in all three pair-wise comparisons, and hence were considered to be the most highly affected transcripts by mutation of Bmp15 and Gdf9. IPA Analyses revealed that metabolism was the major theme associated with the most highly-changed transcripts: glycolysis and sterol biosynthesis were the two most significantly affected pathways. Most of the transcripts encoding enzymes for sterol biosynthesis were down-regulated in both mutant cumulus cells and in WT cumulus cell after oocytectomy. Similarly, there was a reduction of de novo-synthesized cholesterol in these cumulus cells. This suggests that oocytes regulate cumulus cell metabolism, particularly sterol biosynthesis, by promoting the expression of corresponding transcripts. Furthermore, in WT-mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol, and Ebp, which encode enzymes in the sterol biosynthetic pathway, were found to be expressed robustly in cumulus cells, but expression was barely detectable in oocytes. Levels of de novo-synthesized cholesterol were significantly higher in cumulus–enclosed oocytes than denuded oocytes. These results indicate that mouse oocytes are deficient in their ability to synthesize cholesterol and require cumulus cells to provide them with products of the sterol biosynthetic pathway. Oocyte-derived BMP15 and GDF9 may promote this metabolic pathway in cumulus cells as compensation for their own deficiencies. Keywords: Gdf9, Bmp15, cumulus cells, transcriptome, metabolism, sterol biosynthesis, genotype comparison, microarray, ingenuity pathways analyses.
2007-10-22 | GSE7225 | GEO
Project description:Follicle stimulating hormone (FSH) and epidermal growth factor (EGF) are currently used on cumulus-oocyte complexes to mimic the luteinizing hormone surge in vitro and induce oocyte maturation and cumulus expansion. We have previously shown that addition of exogenous recombinant growth differentiation factor 9 (GDF9) during oocyte in vitro maturation led to an improvement of oocyte quality, as shown by an increased blastocyst percentage and fetal survival. Our objective was to characterize the effect of FSH/EGF and GDF9 treatments on mouse cumulus cells expression profile by microarray analysis. Cumulus-oocyte complexes (COCs) were recovered from 21 to 26 day old female 129/SV mice, 44 hours post equine chorionic gonadotropin treatment (eCG (5 IU)). For the microarray experiment whole COCs were treated with 293H control medium (0.125% v/v), with 20 ng/ml GDF9 or with a combination of 50 mIU/ml FSH and 10 ng/ml EGF. After 8 hours of in vitro maturation, COCs were denuded by gentle pipetting, the oocytes were removed and the cumulus cells centrifuged and extracted RNA analysed by microarray.
2011-12-10 | E-GEOD-19327 | biostudies-arrayexpress
Project description:Identification and characterization of the changed and stable transcripts during mouse oocyte maturation
| PRJNA96947 | ENA
Project description:In mammals, members of the transforming growth factor-beta (TGF-beta) superfamily are known to have key roles in the regulation of follicular growth and development. The aim of the study was to evaluate the expression of TGF-beta superfamily growth factors, their receptors and downstream SMAD signalling molecules during early human folliculogenesis. Human preantral follicles were enzymatically isolated from surplus ovarian tissue obtained from women having ovarian cortical tissue frozen for fertility preservation. A total of 348 human preantral follicles, ranging from 40 to 200 um in diameter, were isolated from ovarian tissue obtained from 15 women, aged 24M-^V34 years. Isolated preantral follicles were grouped according to diameter in five size-matched populations spanning the primordial, primary and secondary stage follicles, and analyzed by whole-genome microarray analysis. Selected proteins/genes were analysed by immunocytochemistry and quantitative RT-PCR. TGF-beta superfamily genes with overall highest mRNA expressions levels included growth differentiation factors 9 (GDF9), bone morphogenic protein-15 (BMP15), BMP6, BMP-receptor-2 (BMPR2), anti-MM-|llerian hormone receptor 2 (AMHR2), TGFbetaR3, inhibin-alpha (INHA), and intracellular SMAD3 and SMAD4. Moreover, genes which were differentially expressed from the primordial to the late secondary stage follicles included GDF9 (p<0.01), BMP15 (p<0.001), AMH (p<0.0001), INHBB (p<0.05), TGFbetaR3 (p<0.05) and SMAD4 (p<0.05). Collectively, these data indicate that the active TGF-beta superfamily pathways in early human folliculogenesis consist of primarily GDF9 combined with synergistic effects of BMP15 through the BMPR2 and intracellular activation of SMAD3 and SMAD4, and that AMH and Inhibin B are engaged in intrafollicular events from the onset of follicular growth.
2013-08-06 | E-MEXP-3783 | biostudies-arrayexpress
Project description:Follicle stimulating hormone (FSH) and epidermal growth factor (EGF) are currently used on cumulus-oocyte complexes to mimic the luteinizing hormone surge in vitro and induce oocyte maturation and cumulus expansion. We have previously shown that addition of exogenous recombinant growth differentiation factor 9 (GDF9) during oocyte in vitro maturation led to an improvement of oocyte quality, as shown by an increased blastocyst percentage and fetal survival. Our objective was to characterize the effect of FSH/EGF and GDF9 treatments on mouse cumulus cells expression profile by microarray analysis.
2011-12-10 | GSE19327 | 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 ≈1 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.
2012-09-01 | GSE38315 | 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:Purpose: The goal of this study is to compare oocyte transcriptome profiling in WT and Kat8 Gdf9 cKO mice Methods: Oocyte mRNA profiles of 2 weeks old WT and Kat8 Gdf9 cKO mice were generated by deep sequencing using Illumina HiSeq 2500. Results: Using an optimized data analysis workflow, we mapped about 54-63 million sequence reads per sample to the mouse genome (build mm10) and identified 18,468 transcripts in the oocytes of WT and Kat8 Gdf9 cKO mice. Approximately 5% of the transcripts showed differential expression between the WT and Kat8 Gdf9 cKO oocyte, with a fold change ≥1.5 and p value <0.05. Conclusions: Our study represents the first detailed analysis of oocyte transcriptomes after kat8 deletion, which is generated by RNA-seq technology.Our results show that Kat8 affects numerous gene expression in mouse oocytes.
2017-03-25 | GSE97026 | GEO
Project description:Transcriptomes of mouse mural granulosa cells were sequenced to identify transcripts expressed in mural granulosa cells of ovaries. Moreover, transcriptomes of cumulus cells were compared between those of young (2 month-old) and old mice (10 month-old) to assess the effects of ageing on cumulus cells. In addition, transcriptomes of cumulus-oocyte complexes were compared between DBA/2 and (C57BL/6 x DBA/2)F1 mice to assess the strain differences.
2016-04-15 | GSE80326 | GEO