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

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

PROVIDER: PRJNA1099237 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28628921_1.fastq.gz	Fastqsanger.gz
	SRR28628921_2.fastq.gz	Fastqsanger.gz
	SRR28628922_1.fastq.gz	Fastqsanger.gz
	SRR28628922_2.fastq.gz	Fastqsanger.gz
	SRR28628923_1.fastq.gz	Fastqsanger.gz

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

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

Oocyte-specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early-growing follicles by mitochondrial fission defect-reactive oxygen species-DNA damage.

Project description: Not available

| S-EPMC11306288 | biostudies-literature

A Tale of Two Follicles: Proteomic Clues to Oocyte Success and Failure

Project description:Women are born with thousands of follicles in their ovaries but less than 1% will produce a mature oocyte. What distinguishes the 99% of ovarian follicles destined for demise from the rare 1% that succeed? Here, we leveraged a unique clinical opportunity, paired follicular fluid samples from small antral follicles containing viable and atretic oocytes, to uncover the proteomic determinants governing oocyte fate. Our analysis identified nearly 1,500 proteins, revealing that healthy follicular fluid is enriched with proteins crucial for energy metabolism, antioxidative defense, structural integrity, and robust signaling networks, supporting successful oocyte survival and maturation. In contrast, atretic follicles exhibited a distinct inflammatory signature characterized by acute-phase and immune activation proteins, indicative of active degeneration. These novel proteomic insights deepen our understanding of follicle biology and open new avenues for biomarker development, optimization of assisted reproductive technologies, and targeted therapeutic strategies to preserve and enhance female fertility.

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Proteome of fluid from human small antral follicles reveals insights in folliculogenesis and oocyte maturation.

Project description:Human ovarian follicles develop a fluid-filled antrum when they reach a diameter of around 250 µm. The antrum contains follicular fluid (FF) composed of secretions from cells in the follicle and from circulation. The composition of FF undergoes massive changes in relation to follicular development. Previously, only FF from large pre-ovulatory follicles aspirated just prior to ovulation, has been analyzed by proteomics; resulting in a high proportion of plasma proteins being detected due to diffusion of proteins through the increasingly leaky basal membrane in larger follicles. We present the first proteomics analysis of FF from normal unstimulated human small antral ovarian follicles (diameter: 3-8mm) identifying the largest number of proteins reported in human FF to date: 2,050 proteins of which 1,151 were identified for the first time in human FF by mass spectrometry. Furthermore, an identified growth factor, midkine, was shown to impact follicular regulatory processes including enhancement of nuclear maturation of immature human oocytes.

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Dynamic changes in gene expression of growing nonhuman primate antral follicles

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Bovine granulosa cells of dominant follicles; comparison of growing vs atretic

Project description:Granulosa cells originating from two different phases of antral follicle growth (growing and atresia) were compared in follicles with a diameter of 9mm or more. Growing follicle is the reference.

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Bovine granulosa cells of dominant follicles; comparison of growing vs plateau

Project description:Granulosa cells originating from two different phases of antral follicle growth (growing and plateau) were compared in follicles with a diameter of 9mm or more. Growing follicle is the reference.

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Proteome of fluid from human ovarian small antral follicles reveals insights in folliculogenesis and oocyte maturation.

Project description:Protein composition of human ovarian follicular fluid (FF) constitutes the microenvironment for oocyte development. Several proteomics studies of FF from pre-ovulatory follicles have revealed insights on oocyte maturation, however, there is a lack of knowledge on changes produced at protein levels in the FF of human small antral follicles (hSAF) related to the upcoming oocyte maturation. Using mass spectrometry-based proteomics, we evaluated the protein composition of FF that surrounds oocytes capable to reach metaphase II (MII) after IVM with the protein profile of FF that surrounds immature oocytes. The samples were collected from small antral follicles (size 6.0 ± 1.5 mm) extracted from six women, from which two or three samples were extracted. The comparison was based on both, a multivariate (sPLS-DA) and univariate analyses (t-test).

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Transcriptional profiling of somatic cells differentiation throughout oocyte competence acquisition in the xenopus ovarian follicles.

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