Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1057590 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27365415_1.fastq.gz | Fastqsanger.gz | |||
| SRR27365415_2.fastq.gz | Fastqsanger.gz | |||
| SRR27365416_1.fastq.gz | Fastqsanger.gz | |||
| SRR27365416_2.fastq.gz | Fastqsanger.gz | |||
| SRR27365417_1.fastq.gz | Fastqsanger.gz |
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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:Mitochondrial DNA quantity Counteracts ROS damage in oocytes during female reproductive aging
| PRJNA1055145 | ENA
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:Copper (Cu) is not only one of the essential trace elements for animal body, but also an important nutrient component for normal physiology and metabolism of animal reproductive system. Lack or excess of copper will directly or indirectly affect animal reproductive activities. However, the effect of copper on reproductive performance of boars and sows has not been studied and the effect of excessive Copper addition on reproductive performance of sows is even less, and the molecular mechanism is poorly understood. Here, we document that copper has the negative effects on the oocyte maturation and Organelle function. We show that copper exposure perturbs the porcine oocyte meiotic maturation and impair the spindle/chromosome structure, displaying an obviously defective spindle assembly, and abnormal distribution of actin dynamics and cortical granules. In addition, single-cell transcriptome analysis identifies target effectors of copper in porcine oocytes, which was further demonstrated that copper exposure affects the distribution and function of mitochondria, and high ROS levels, DNA damage, and early apoptosis in porcine oocytes. Collectively, we demonstrate that copper exposure causes abnormalities in mitochondrial function and distribution, resulting in increased oxidative stress ROS levels, DNA damage and apoptosis, ultimately leading to decreased quality of porcine oocytes.
2021-06-28 | GSE168867 | GEO
Project description:In our study, scWES was employed on oocytes from female mice with different reproductive ages. We also performed whole exome sequencing on bluk blood samples in trios to detect de novo germline variations in oocytes. Both natural aging and accelerated reproductive aging were involved. We demonstrated that genetic alterations, including base variants and structural variations, occurred in mouse oocytes during aging. Genes harboring natural aging or accelerated aging-related de novo germline variants (DNGVs) were almost involved in Ugt1a, V2R, and Mucin gene families. A copy number variant (CNV) associated with chromatin modeling were detected in natural aging oocytes. More importantly, we shortlisted various critical biological functions, like calcium binding pathway and p53 pathways, affected by these aging-related genetic alterations. Our work is the first study to identify genetic alterations in mouse oocytes with in vivo aging and offers a new direction of dissecting the aging mechanisms in oocytes and clarifying genetic causes of lower fertility at advanced maternal age.
2019-08-01 | PRJEB28344 | EVA
Project description:Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI). Here, we demonstrate that the conditional knockout of eukaryotic translation initiation factor 5 (Eif5) in both mouse primordial and growing oocytes resulted in the apoptosis of oocytes within the early growing follicles. The further studies revealed that Eif5 deletion in oocytes downregulated the levels of mitochondrial fission-related proteins (FIS1, MFF, MTFR2 and p-DRP1) and upregulated the levels of the integrated stress response (ISR)-related proteins (SLC7A1, SHMT2 and AARS1) and genes (Atf4, Ddit3 and Fgf21). Consistent with this, Eif5 deletion in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased ATP content and mtDNA copy number, and excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Meanwhile, Eif5 deletion in oocytes led to a significant increase in the levels of DNAdamageresponse proteins (γH2AX, p-CHK2, and p53) and proapoptotic proteins (PUMA and BAX), as well as a significant decrease in the levels of anti-apoptotic protein BCL-xL. Collectively, these findings indicate that Eif5 deletion in mouse oocytes results in the apoptosis of oocytes within the early growing follicles via mitochondrial fission defect and excessive ROS-induced DNA damage. This study provides new insights into pathogenesis and genetic diagnosis for POI.
2024-08-15 | GSE263785 | GEO
Project description:Exercise is a fundamental component of human health that is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of endurance exercise on human health are well established, the molecular mechanisms responsible for these observations remain unclear. Endurance exercise reduces the accumulation of mitochondrial DNA (mtDNA) mutations, alleviates multisystem pathology, and increases the lifespan of the mtDNA mutator mouse model of aging, in which the proof-reading capacity of mitochondrial polymerase gamma (POLG1) is deficient. Clearly, exercise recruited a POLG1-independent mtDNA repair pathway to induce these adaptations, a novel finding as POLG1 is canonically considered to be the sole mtDNA repair enzyme. Here we investigate the identity of this pathway, and show that endurance exercise prevents mitochondrial oxidative damage, attenuates telomere erosion, and mitigates cellular senescence and apoptosis in mtDNA mutator mice. Unexpectedly, we observe translocation of tumour suppressor protein p53 to mitochondria in response to endurance exercise that facilitates mtDNA mutation repair. Indeed, endurance exercise failed to prevent mtDNA mutations, induce mitochondrial biogenesis, preserve mitochondrial morphology, reverse sarcopenia, and mitigate premature mortality in mtDNA mutator mice with muscle-specific deletion of p53. Our data establish an exciting new role for p53 in exercise-mediated maintenance of the mtDNA genome, and presents mitochondrially-targeted p53 as a novel therapeutic modality for aging-associated diseases of mitochondrial etiology. Microarray analysis of gene expression from skeletal muscle (quadriceps femoris) from Mus musculus. N=23 samples per treatment were analysed for whole transcriptiome gene expression profile using NimbleGen Arrays. The treatment groups included wild-type C57Bl/6J mice as the control group, then two treatment groups which both contained homozygous knock-in mtDNA mutator mice (PolG; PolgAD257A/D257A). Once group of these heterozygous knock out mice received regular endurance exercise sessions while the other group remained sedentraty for 6 months. The control group specimens were wild-type litter mates to the transgenic knockout mice.
2015-12-11 | E-GEOD-75869 | biostudies-arrayexpress
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:Mitochondrial DNA (mtDNA) mutations may contribute to aging and age-related disorders. Previously, we created mice expressing a proofreading-deficient version of the mtDNA polymerase gamma (Polg) which accumulate age-related mtDNA mutations and display premature aging. Here we performed microarray gene expression profiling to identify mtDNA mutation-responsive genes in the cochlea of aged mitochondrial mutator mice. Age-related accumulation of mtDNA mutations was associated with transcriptional alternations consistent with reduced inner ear function, mitochondrial dysfunction, neurodegeneration, and reduced cell structural modulation. Hearing assessment and histopathological results confirmed that aged PolgD257A/D257A (D257A) mice exhibited moderate hearing loss and severe cochlear degenerations. Age-related accumulation of mtDNA mutations also resulted in alternations in gene expression consistent with induction of apoptosis, proteolysis, stress response, and reduced DNA repair. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay confirmed that the cochleae from aged D257A mice showed significantly more TUNEL positive cells compared to wild-type (WT) mice. The levels of cleaved caspase-3 were also found to increase in the cochleae of aged D257A mice. These observations provide evidence that age-related accumulation of mtDNA mutations is associated with apoptotic cell death in aged cochlea. Our results provide the first global view of molecular events associated with mtDNA mutations in postmitotic tissue, and suggest that apoptosis is the major mechanism of mtDNA mediated cell death in the development of age-related hearing disorder. Experiment Overall Design: To determine the effects of age-related accumulation of mtDNA mutations, each WT sample (n = 5) was compared to each D257A sample (n = 5), generating a total of twenty-five pairwise comparisons. Genes with significantly altered expression levels were sorted into gene ontology biological process categories. Experiment Overall Design: Gene expression change was called statistically significant when at least one gene was called present in a group, the P value was < 0.0500, FC was > 1.1, and FDR was > 30.00 for identification of mtDNA mutations-induced genes. Experiment Overall Design: Affymetrix standard spike controls were used in all experiments (eukaryotic hybridization control kit). Quality control measures were not used. No replicates were done. Dye swap was not used.
2008-11-07 | E-GEOD-4866 | biostudies-arrayexpress
Project description:Exercise is a fundamental component of human health that is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of endurance exercise on human health are well established, the molecular mechanisms responsible for these observations remain unclear. Endurance exercise reduces the accumulation of mitochondrial DNA (mtDNA) mutations, alleviates multisystem pathology, and increases the lifespan of the mtDNA mutator mouse model of aging, in which the proof-reading capacity of mitochondrial polymerase gamma (POLG1) is deficient. Clearly, exercise recruited a POLG1-independent mtDNA repair pathway to induce these adaptations, a novel finding as POLG1 is canonically considered to be the sole mtDNA repair enzyme. Here we investigate the identity of this pathway, and show that endurance exercise prevents mitochondrial oxidative damage, attenuates telomere erosion, and mitigates cellular senescence and apoptosis in mtDNA mutator mice. Unexpectedly, we observe translocation of tumour suppressor protein p53 to mitochondria in response to endurance exercise that facilitates mtDNA mutation repair. Indeed, endurance exercise failed to prevent mtDNA mutations, induce mitochondrial biogenesis, preserve mitochondrial morphology, reverse sarcopenia, and mitigate premature mortality in mtDNA mutator mice with muscle-specific deletion of p53. Our data establish an exciting new role for p53 in exercise-mediated maintenance of the mtDNA genome, and presents mitochondrially-targeted p53 as a novel therapeutic modality for aging-associated diseases of mitochondrial etiology.
2015-12-11 | GSE75869 | GEO