Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oocyte-specific deletion of Eif5 causes apoptosis of mouse oocytes within the early growing follicles by mitochondrial fission defect and DNA damage

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE263785 | GEO | 2024/08/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Oocyte-specific deletion of Eif5 causes apoptosis of mouse oocytes within the early growing follicles by mitochondrial fission defect and DNA damage

Project description:Oocyte-specific deletion of Eif5 causes apoptosis of mouse oocytes within the early growing follicles by mitochondrial fission defect and DNA damage

| PRJNA1099237 | ENA

Theophylline derivatives promote the activation of primordial follicles and ameliorate fertility deficits in naturally aged mice

Project description:The residual dormant primordial follicles in aged women and patients with premature ovarian insufficiency (POI) are difficult to activate in vivo. In this study, we found that PDE1A, PDE2A and PDE6D were expressed mainly in mouse primordial follicle oocytes and that PDE1A and PDE2A levels were significantly decreased during the activation of primordial follicles. The specific inhibitors of PDE1 (nimodipine), PDE2 (EHNA) and PDE5/6 (zaprinast) and the nonspecific PDE inhibitors theophylline derivatives (including aminophylline, dyphylline, enprofylline, choline theophyllinate, doxofylline, arofylline and lisofylline) activated mouse primordial follicles. These inhibitors also increased the levels of cyclic adenosine monophosphate (cAMP) and phosphorylated protein kinase B (p-Akt) in cultured mouse ovaries. Moreover, the administration of aminophylline, dyphylline and enprofylline to neonatal mice by intraperitoneal injection and to adolescent mice by oral treatment increased the number of growing follicle and the levels of p-Akt in the ovaries. Importantly, the oral administration of aminophylline increased the quantity and quality of ovulated oocytes and the number of offspring in naturally aged mice. In addition, aminophylline, dyphylline and enprofylline activated human primordial follicles and increased p-Akt levels. Thus, theophylline derivatives activate primordial follicles by increasing cAMP levels and activating the PI3K/Akt pathway, and the oral administration of aminophylline increases fertility in naturally aged female mice. As oral medications, theophylline derivatives may be used to increase fertility in aged women and patients with POI.

2024-05-30 | GSE263843 | GEO

Prolonged pause during follicle growth contributes to offspring throughout reproductive lifespan

Project description:Ovulation results from cyclical recruitment of quiescent oocytes for growth, hence the primordial follicles established during development comprise the lifelong reserve. In mouse fetal oocytes, we lineage traced a subset with earlier onset and slower progression through meiotic prophase using Sycp3CreERT2/+; Rosa26nT-nG/+ females. Initially GFP labeled first meiotic entrants survived at elevated rates and contributed to primordial follicles as well as the first wave of growing follicles in neonates. However, by puberty, only oocytes in the first wave of growing follicles remained. To identify the transcriptional signature of GFP+ oocytes in growing follicles, we performed Bulk RNA sequencing, which revealed remarkable similarity between the transcriptomes of GFP+ (first meiotic entrants) and RFP+ (the rest of the oocytes), with only 12 genes showing differential expression.

2024-10-08 | GSE272099 | GEO

oocyte miRNA profiling by array

Project description:This study compares miRNA expression profiles in mouse oocytes as young oocytes vs aged oocytes, and growing oocytes vs small oocytes from primordial follicles.

2012-09-04 | GSE17966 | GEO

RNA-Seq Facilitates Quantitative Analysis of Wild Type and Bnc1tr/tr ovary Transcriptomes

Project description:Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, serious daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We have previously identified Basonuclin1 (BNC1) mutation from a large Chinese POI pedigree and find the targeted Bnc1 mutation mouse exhibites POI. In this study, we find that BNC1 plays a key role in the dynamic balance of ovarian reserve, and maintaining lipid metabolism and redox homeostasis in oocytes during follicular development. Deficiency of BNC1 results in premature follicular activation and accelerated follicular atresia, but doesn’t affect the ovarian primordial follicle reserve. Mechanistically, BNC1 targets the NF2-YAP pathway to trigger oocyte ferroptosis. Inhibition of ferroptosis significantly rescues POI. These findings uncover a novel pathologic mechanism of POI based on BNC1 deficiency and is the first report showing ferroptosis involved in oocyte death.

2022-08-31 | GSE194196 | GEO

RNA-Seq Facilitates Quantitative Analysis of Wild Type and Bnc1tr/tr oocyte Transcriptomes

2022-08-31 | GSE194194 | GEO

Genome-wide maps of chromatin state in Wild Type mouse ovary

2022-08-31 | GSE194195 | GEO

Human platelet-rich plasma promotes the primordial follicle activation through the PI3K/Akt signaling pathway

Project description:The activation of dormant primordial follicles is a promising method for rescuing the infertility of aged women and premature ovarian insufficiency (POI) patients. Accumulating evidences in both human and animal suggest that human platelet-rich plasma (hPRP) has the ability to recover ovarian function and promote follicle growth, however the underlying mechanisms remain unclear. In the current study, we revealed that hPRP promoted the activation of primordial follicles and the proliferation of granulosa cells. hPRP treatments significantly increased the levels of phosphorylated protein kinase B (Akt) and forkhead Box O3a (FOXO3a), and the number of oocytes with FOXO3a nuclear export. The hPRP-induced primordial follicle activation could be blocked by LY294002, the inhibitor of PI3K/Akt. By in vivo injection newborn mice model and in vitro culture human ovarian fragments, hPRP was further proved to be effective in the activation of primordial follicles. Taken together, our results suggest that hPRP can promote the primordial follicle activation through the PI3K/Akt pathway. Our results provide a theoretical basis for the clinical application of hPRP in aged women and POI patients.

2024-09-01 | GSE263743 | GEO

Primordial follicle formation involves dynamic conversion of RNA regulatory proteins (RIP-seq data set)

Project description:Long-term reproductive ability in mammalian females is sustained by the successive consumption of the finite pool of primordial follicles, the most primitive ovarian follicles that arise from cystic-oocytes during oogenesis. However, mechanisms underlying the formation of primordial follicles are largely unknown. Here we show that dynamic conversion of RNA-regulatory proteins precedes the formation of primordial follicles in mice. We find that, whereas stress granules dominate in cystic-oocytes, those are replaced by processing-bodies prior to the formation of primordial follicles that coincide with the expression of an evolutionally conserved RNA-binding protein, DDX6. Targeted deletion of Ddx6 disrupts processing-body assembly and perturbs cyst-breakdown. Furthermore, these events are orchestrated by an RNA-binding protein, ELAVL2. Our data suggest that cystic-oocytes switch post-transcriptional mechanism for upcoming formation of primordial follicles.

2018-09-30 | GSE113304 | GEO

Early Postnatal Alterations in Follicular Stress Response and Survival in a Mouse Model of Classic Galactosemia

Project description:Primary ovarian insufficiency (POI) is characterized by accelerated loss of primordial follicles, which results in ovarian failure and concomitant menopause before age 40. 1-3% of females in the general population are diagnosed with POI and 80% of females with the inherited disease Classic Galactosemia (CG) will develop POI. CG is caused by mutations in the GALT gene encoding the enzyme galactose-1-phosphate uridylyltransferase. While dietary restriction of galactose is lifesaving in the neonatal period, the development of severe complications including POI is not mitigated. Additionally, the pattern of follicle loss have not been completely characterized. The chronic accumulation of aberrant metabolites such as galactose-1 phosphate and galactitol are the suspected culprits in the development of the sequelae, yet the mechanisms remain elusive. Our group uses a GalT gene-trapped mouse model to study the pathophysiology of CG. Recently, we showed that alterations in the Integrated Stress Response pathway occur in the ovaries of these mice, likely contributing to the POI phenotype. Using immunofluorescent staining in whole-ovary histology at progressive ages, we saw evidence of altered Integrated Stress Response activity in granulosa cells and primordial oocytes leading to accelerated primordial follicle growth, aberrant DNA damage repair, and increased cellular stress/death. RNA-sequencing of whole ovary revealed significant alterations in cholesterol/lipid metabolism and transcriptional regulation. Overall, our findings indicate abnormal stress response results in accelerated primordial follicle activation or “burnout,” which may explain the POI phenotype of fewer primordial follicles at later ages.

2023-02-01 | GSE196454 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data