Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA193681 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:During female reproductive life, the reserve of ovarian follicles is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. We asked if overexpression of a constitutively active FOXO3 protein can increase long-lasting ovarian reproductive capacity in mice. Trangenic vs non-transgenic mice onto Foxo3+/- vs Foxo3-/- genotype
2013-06-08 | E-GEOD-45389 | biostudies-arrayexpress
Project description:During female reproductive life, the reserve of ovarian follicles is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. We asked if overexpression of a constitutively active FOXO3 protein can increase long-lasting ovarian reproductive capacity in mice.
2013-06-08 | GSE45389 | GEO
Project description:Although it is well established that the ovarian reserve diminishes with increasing age, and that a woman’s age is correlated to lower oocyte quality, the interplay of a diminished reserve and age on oocyte developmental competence is not clear. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activation (EGA) relies on maternal RNA and proteins. Age and ovarian reserve both affects oocyte developmental competence, however, their relative importance in this process are difficult to tease out, as ageing is accompanied by a decrease in ovarian reserve. Oocytes store large quantities of RNA, including several noncoding transcripts (ncRNAs) involved in early development transcription and translation modulation. Despite the central role of ncRNAs in maternal to zygote transition, no characterization of the ncRNA transcriptome in human oocytes has been reported. This study aims at identifying how the human oocyte transcriptome changes across reproductive ages and ovarian reserve levels, with the goal of identifying candidate markers of developmental competence, and to assess the independent relevance of age and ovarian reserve in the changes of the transcriptome
2017-08-29 | GSE87201 | GEO
Project description:The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.
2022-06-26 | GSE184208 | GEO
Project description:We have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis. We sought to determine the transcriptional differences in forebrains from E12.5 mice expressing a constitutively active alleleof FoxO3 under the control of the forebrain-specific CaMKIIa promoter. To this end two time-pregnant dams were sacrificed 12 days after the vaginal plug was detected, and the embryos were prepared. Visual staging of the embryos confirmed their age. Genotyping and luciferase measurements were performed in order to assess presence and acitivity of the transgenes.
2012-09-13 | E-GEOD-21089 | biostudies-arrayexpress
Project description:Expression of constitutively active FOXO3 in murine forebrain leads to a loss of neural progenitors
| PRJNA126707 | ENA
Project description:In mammals, most immature oocytes remain dormant in the primordial follicles in order to ensure the longevity of female reproductive life. A precise understanding of mechanisms underlying the dormancy is important for reproductive biology and medicine. In this study, by comparing mouse oogenesis in vivo and in vitro, the latter of which bypasses the primordial follicle stage, we defined the gene expression profile representing the dormant state of oocytes. Overexpression of constitutively active FOXO3 partially reproduced the dormant state in vitro. Based on further gene expression analysis, we found that a hypoxic condition efficiently induced the dormant state in vitro. The effect of hypoxia was severely diminished by disruption of the Foxo3 gene and inhibition of hypoxia-inducible factors. Our findings provide insights into the importance of environmental conditions and their effectors for establishing the dormant state.
2019-05-28 | GSE128305 | GEO
Project description:In the nervous system, neural stem cells (NSC) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3-/- mice have fewer NSC in vivo than wild type counterparts. NSC isolated from adult FoxO3-/- mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSC suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSC might have important implications for counteracting brain aging in long-lived species. Experiment Overall Design: mRNA expression from secondary neurospheres cultured from cells taken from mouse forebrains was compared between FoxO3+/+ (wildtype) and FoxO3-/- (null mutant) mice from the FVB/N background.
2009-12-05 | E-GEOD-18326 | biostudies-arrayexpress
Project description:We have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis.
2012-09-13 | GSE21089 | GEO
Project description:Following proliferation of oogonia inmammals, great numbers of germ cells are discarded, primarily by apoptosis, while the remainder form primordial follicles (the ovarian reserve) that determine fertility and reproductive lifespan. More massive, rapid, and essentially total loss of oocytes, however, occurs when the transcription factor Lhx8 is ablated—though the cause and mechanism of germ cell loss from the Lhx8-/- ovaries has been unknown. We found that Lhx8−/− ovaries maintain the same number of germ cells throughout embryonic development; rapid decrease in the pool of oocytes starts shortly before birth. The loss results from activation of autophagy, which becomes overwhelming within the first postnatal week, with extracellular matrix proteins filling the space previously occupied by follicles to produce a fibrotic ovary. Associated with this process, as early as a few days before birth, Lhx8-/- oocytes failed to repair DNA damage—which normally occurs when meiosis is initiated during embryonic development; and DNA damage repair genes were downregulated throughout the oocyte short lifespan. Based on gene expression analyses and morphological changes, we propose a model in which lineage-restricted failure of DNA repair triggers germ cell autophagy, causing premature depletion of the ovarian reserve in Lhx8-/- mice
2019-01-22 | GSE109473 | GEO