Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA397184 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5898360_1.fastq.gz | Fastqsanger.gz | |||
| SRR5898360_2.fastq.gz | Fastqsanger.gz | |||
| SRR5898370_1.fastq.gz | Fastqsanger.gz | |||
| SRR5898370_2.fastq.gz | Fastqsanger.gz | |||
| SRR5898361_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:The peptidase ClpP is conserved from bacteria to human. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder. Because of its known relevance for the mitochondrial unfolded protein response during cell stress, we characterized two ClpP knock-out mouse founder lines and documented similar phenotypes. Ubiquitously, ClpP absence led to accumulation of its interactor protein ClpX without transcript upregulation. Interestingly, most wild-type tissues with substantial ClpP amounts had no detectable ClpX. This inverse correlation suggests that ClpX levels and degradation are regulated by ClpP. The expectation of similar protein levels, in view of a reported association of heptameric ClpP rings with hexameric ClpX rings, was confirmed only in testis of wild-type animals. Germline tissue was exceptional also in its vulnerability to ClpP deletion, with both founder lines showing complete infertility for males and females. Otherwise, ubiquitous mitochondrial dysfunction was apparent from severe growth retardation and reduced spontaneous motor activity of the animals, and from a pronounced decrease in pre-/postnatal survival. Spermatogenesis was found aborted at the spermatid stage, acrosomes and axonemes were not formed. Overall, tissue-specific roles of ClpP were evident by this massive effect for germ cells, mild bioenergetic deficits in muscle and liver tissues, and excellent compensation in brain. ClpX was previously reported to chaperone unfolded proteins and also DNA condensation in mitochondria, so it is likely that this pathway is particularly susceptible in germ cells. In conclusion, our study indicates that the role of ClpP in quality control is indispensable during development for cells with rapid changes of mitochondrial numbers, and is relevant during aging for growth and survival of the organism. Factorial design comparing ClpP knock-out mice with wild type littermates in five different tissues (brain, testis, liver, skeletal and heart muscle)
2013-07-17 | E-GEOD-40207 | biostudies-arrayexpress
Project description:We investigated the contentious role of mitochondrial reactive oxygen species (ROS) on mitochondrial DNA (mtDNA) quality and quantity in female reproductive aging. By conditionally knocking out the Sod2 gene in female mouse germline, we observed increased mitochondrial ROS and decreased oocyte quality, primarily due to impacts on OXPHOS complex II and mtDNA encoded mRNA levels. Interestingly, we found no increased mtDNA mutations, but alterations in mtDNA quantity, indicating the susceptibility of mtDNA to the mitochondrial ROS during reproductive aging. Notably, when we further decreased the basal level of mtDNA quantity by deactivating the mtSSB protein in Sod2 conditional knockout females, we observed an exacerbation of reproductive aging effects. This highlights the crucial role of mtDNA quantity in mitigating the impact of oxidative stress on fertility.
2024-09-09 | GSE251734 | GEO
Project description:The peptidase ClpP is conserved from bacteria to human. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder. Because of its known relevance for the mitochondrial unfolded protein response during cell stress, we characterized two ClpP knock-out mouse founder lines and documented similar phenotypes. Ubiquitously, ClpP absence led to accumulation of its interactor protein ClpX without transcript upregulation. Interestingly, most wild-type tissues with substantial ClpP amounts had no detectable ClpX. This inverse correlation suggests that ClpX levels and degradation are regulated by ClpP. The expectation of similar protein levels, in view of a reported association of heptameric ClpP rings with hexameric ClpX rings, was confirmed only in testis of wild-type animals. Germline tissue was exceptional also in its vulnerability to ClpP deletion, with both founder lines showing complete infertility for males and females. Otherwise, ubiquitous mitochondrial dysfunction was apparent from severe growth retardation and reduced spontaneous motor activity of the animals, and from a pronounced decrease in pre-/postnatal survival. Spermatogenesis was found aborted at the spermatid stage, acrosomes and axonemes were not formed. Overall, tissue-specific roles of ClpP were evident by this massive effect for germ cells, mild bioenergetic deficits in muscle and liver tissues, and excellent compensation in brain. ClpX was previously reported to chaperone unfolded proteins and also DNA condensation in mitochondria, so it is likely that this pathway is particularly susceptible in germ cells. In conclusion, our study indicates that the role of ClpP in quality control is indispensable during development for cells with rapid changes of mitochondrial numbers, and is relevant during aging for growth and survival of the organism.
2013-07-17 | GSE40207 | GEO
Project description:Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that spermidine level was reduced in aged ovaries and supplementation of spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By micro-transcriptomic analysis, we further discovered that recovery of oocyte quality by spermidine was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this action mechanism was conserved in porcine oocytes under oxidative stress. Altogether, our findings demonstrate that spermidine supplementation is a potentially effective strategy to ameliorate oocyte quality and reproductive outcome of women at an advanced age.
2023-11-10 | GSE239551 | GEO
Project description:We performed RNAseq analysis to determine the effect of ClpP-deletion on cumulus cells global gene expression profile in mature (3 month-old) and (6 month-old) mice. RNA sequencing revealed about 13,000 genes (FPKM > 0.1) expressed in cumulus cells. A total of 1025 genes were significantly differentially expressed (p<0.05) in 3-month ClpP-/- cumulus cells compared to WT (548 up-regulated and 477 down-regulated). At 6-month, a total of 555 genes were significantly differentially expressed in ClpP-/- cumulus cells compared to WT (464 up-regulated and 91 down-regulated). In addition, 1012 and 1034 genes were significantly differentially expressed in both 6 month ClpP-/- and WT cumulus cells compared to younger ClpP-/- cumulus cells, respectively. In this study, we assessed the effect of ClpP global deletion on cumulus cells gene expression. Our findings provide new insight into the role of CLPP in the cumulus cells, and may help understand the potential mechanism of infertility and reproductive aging associated with ClpP-deficiency.
2020-08-15 | GSE102756 | GEO
Project description:We performed RNAseq analysis to determine the effect of ClpP-deletion on cumulus cells global gene expression profile in mature (3 month-old) and (6 month-old) mice. RNA sequencing revealed about 13,000 genes (FPKM > 0.1) expressed in cumulus cells. A total of 1025 genes were significantly differentially expressed (p<0.05) in 3-month ClpP-/- cumulus cells compared to WT (548 up-regulated and 477 down-regulated). At 6-month, a total of 555 genes were significantly differentially expressed in ClpP-/- cumulus cells compared to WT (464 up-regulated and 91 down-regulated). In addition, 1012 and 1034 genes were significantly differentially expressed in both 6 month ClpP-/- and WT cumulus cells compared to younger ClpP-/- cumulus cells, respectively. In this study, we assessed the effect of ClpP global deletion on cumulus cells gene expression. Our findings provide new insight into the role of CLPP in the cumulus cells, and may help understand the potential mechanism of infertility and reproductive aging associated with ClpP-deficiency.
2017-12-01 | GSE102269 | GEO
Project description:The mechanisms contributing to age-related deterioration of the female reproductive system are complex but aberrant protein homeostasis is a major contributor. We elucidated the exceptionally stable proteins, structures, and macromolecules that persist in ovaries and gametes throughout the reproductive aging timeline in mammals. Ovaries exhibit localized structural and cell-type specific enrichment of stable macromolecules throughout both the follicular and extrafollicular environments. Moreover, both ovaries and oocytes harbor a panel of exceptionally long-lived proteins, including cytoskeletal components, mitochondrial, and oocyte-derived proteins. The exceptional persistence of these long-lived molecules might play a critical role in both lifelong maintenance and age-dependent deterioration of reproductive tissues.
2023-06-20 | MSV000092217 | MassIVE
Project description:Aging has many effects on female reproductive system, among which declined oocyte quality and impaired embryo developmental potential are the most important factors affecting female fertility. However, the mechanisms of oocyte aging have not yet been fully understood due to the complex and multifactorial nature of this physiological process. Here, we selected normal reproductively aging female mice as research object and constructed protein expression profile of metaphase II (MII) oocytes from three age groups. A total of 187 differentially expressed (DE) proteins were identified, and bioinformatics analysis showed that these DE proteins were highly enriched in the RNA splicing. Next, RNA-seq was performed on 2-cell embryos from these three age groups, splicing analysis showed that there were a total of 1375 differentially spliced genes (DSGs) and 2363 differentially spliced events (DSEs). DSGs in the reproductive aging groups versus the younger group were enriched in biological processes related to DNA damage repair/response. Binding motif analysis suggested PUF60 may be the core splicing factor that causes the decline of the developmental potential of oocytes in reproductive aging mice, and changing the splicing pattern of its potential downstream DSG Cdk9 could partially mimic phenotypes in the reproductive aging groups. Taken together, our study suggested the abnormal expression of splicing regulation protein in aging MII oocytes will affect the splicing of nascent RNA after zygotic genome activation in 2-cell embryos, leading to the production of abnormally spliced transcripts of some key genes associated with DNA damage repair/response, thus affected the developmental potential of aged oocytes.
2021-11-03 | GSE163724 | GEO
Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology, and its disruption results in infertility. In an effort to identify the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the regulation of ovarian steroidogenic acute regulator (StAR) and its role in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis leads to lower levels of StAR mRNA, and lower progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants results in 100% fertility. Our study suggests that ovarian Bmal1 is an essential peripheral clock governing implantation and fertility in female mice. Ten week old female Bmal1fxfx mice positive or negative for Cre-recombinase driven by the sf-1 promoter, housed in 12 hour light:12 dark, ad lib feeding and drinking conditions were sacrificed at ZT12 on 3.5dpc (3.5 days post copulation). For each array analysis, a pool of 3 RNA samples from 3 individual Bmal1fx/fxCresf-1 ovaries labeled with cy3 were co-hybridized with a pool of 3 RNA samples from Bmal1fx/fx ovaries labeled with cy5, according to Agilent protocols.
2013-02-01 | E-GEOD-38365 | biostudies-arrayexpress
Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology, and its disruption results in infertility. In an effort to identify the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the regulation of ovarian steroidogenic acute regulator (StAR) and its role in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis leads to lower levels of StAR mRNA, and lower progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants results in 100% fertility. Our study suggests that ovarian Bmal1 is an essential peripheral clock governing implantation and fertility in female mice.
2013-02-01 | GSE38365 | GEO