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Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq mouse oocyte]

ABSTRACT: The mechanisms of oocyte meiotic defects and low competence during ovarian aging remains elusive for decades. Using Hi-C (genome-wide chromatin conformation capture) and Smart RNA-seq of oocytes from 6- weeks or 10- months aged ovaries, the abnormal loose chromatin structures and disturbing expression of meiosis associated genes at metaphase I phase were disclosed. Furthermore, the transcriptomic landscape of granulosa cells (GCs) surrounding oocytes from young and aged ovaries reveled that oocyte meiotic maturation was accompanied with a robust increased expression of genes involved with the mevalonate (MVA) pathway in GCs from young ovaries but these genes expression was not upregulated to counterpart level in GCs from aged ovaries.The inhibitor of MVA pathway of GCs, Statins significantly decreased polar body extrusion rate and increased the rate of irregularly assembled spindles and misaligned chromosomes remarkably in oocytes of culumus-oocyte complex (COCs) from young ovaries . Correspondingly, the activitor of MVA pathway of GCs, Geranylgeraniol ameliorated ovarian reserve and reduced meiotic defects in oocytes of COCs from aged ovaries. Mechanistically, MVA pathway activation in GCs culminated oocyte meiotic maturation by upregulating EGF signaling via LH receptor on GCs surrounding oocytes. Together, MVA pathway is a promising therapeutic target for prompting quality of oocytes from aged ovaries.

ORGANISM(S): Mus musculus

PROVIDER: GSE175835 | GEO | 2023/02/26

REPOSITORIES: GEO

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Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq mouse GC]

Project description:The mechanisms of oocyte meiotic defects and low competence during ovarian aging remains elusive for decades. Using Hi-C (genome-wide chromatin conformation capture) and Smart RNA-seq of oocytes from 6- weeks or 10- months aged ovaries, the abnormal loose chromatin structures and disturbing expression of meiosis associated genes at metaphase I phase were disclosed. Furthermore, the transcriptomic landscape of granulosa cells (GCs) surrounding oocytes from young and aged ovaries reveled that oocyte meiotic maturation was accompanied with a robust increased expression of genes involved with the mevalonate (MVA) pathway in GCs from young ovaries but these genes expression was not upregulated to counterpart level in GCs from aged ovaries.The inhibitor of MVA pathway of GCs, Statins significantly decreased polar body extrusion rate and increased the rate of irregularly assembled spindles and misaligned chromosomes remarkably in oocytes of culumus-oocyte complex (COCs) from young ovaries . Correspondingly, the activitor of MVA pathway of GCs, Geranylgeraniol ameliorated ovarian reserve and reduced meiotic defects in oocytes of COCs from aged ovaries. Mechanistically, MVA pathway activation in GCs culminated oocyte meiotic maturation by upregulating EGF signaling via LH receptor on GCs surrounding oocytes. Together, MVA pathway is a promising therapeutic target for prompting quality of oocytes from aged ovaries.

2023-02-26 | GSE175834 | GEO

Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq Human oocytes]

2023-02-26 | GSE175833 | GEO

Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq Human Granulosa cells]

2023-02-26 | GSE175832 | GEO

Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [Hi-C]

2023-02-26 | GSE175830 | GEO

Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [HiC GGOH-treatment]

Project description:The mechanisms of aging-related oocyte aneuploidy remain elusive. Hi-C and SMART-seq revealed aging-related decreases in chromosome condensation, particularly for genomic regions proximal to the centromeres, accompanied with disrupted meiosis-associated gene expression in metaphase I (MI) aged oocytes. Further transcriptomic analysis showed that oocyte meiotic maturation was correlated with robust increases in mevalonate (MVA) pathway gene expression in young oocyte-surrounding granulosa cells (GCs), which was largely downregulated in aged GCs. Inhibtion of MVA metabolism in GCs by statins resulted in marked meiotic defects and aneuploidy in young cumulus-oocyte complexes (COCs). Conversely, supplementation with the MVA isoprenoid geranylgeraniol ameliorated meiotic defects and aneuploidy in aged COCs. Meanwhile, geranylgeraniol also activated LHR/EGF signaling in aged GCs and then enhanced the meiosis-associated gene expression in oocytes. Generally, the MVA pathway in GCs is a critical regulator of meiotic maturation and euploidy in oocytes.

2023-02-26 | GSE212860 | GEO

Rejuvenation of aged oocyte through exposure to young follicular microenvironment

Project description:Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and competence. Follicular somatic cells play crucial roles in the growth and development of the oocyte by providing nutrients and regulatory factors. Here we investigated how oocyte quality is affected by its somatic cell environment by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed. Somatic cells within the chimeric follicle re-establish connections with the oocyte and support oocyte growth and maturation in a three-dimensional (3D) culture system. We show that young oocytes transplanted into aged follicles exhibited reduced meiotic maturation and developmental potential, whereas the young follicular environment significantly improved the rates of maturation, blastocyst formation and live birth of aged oocytes. Aged oocytes cultured within young follicles exhibited enhanced interaction with somatic cells, more youth-like transcriptome, remodelled metabolome, improved mitochondrial function, and enhanced fidelity of meiotic chromosome segregation. These findings provide the basis for a future follicular somatic cell-based therapy to treat age-associated female infertility.

2024-07-22 | GSE270016 | GEO

Cooperation of estrogen and oocytes on gene expression in mouse cumulus cells

Project description:Oocyte-derived paracrine factors and estrogens cooperate to regulate the function and development of mouse cumulus cells. Cumulus oocyte complexes (COCs) were isolated from ovaries of mice. Oocytes were removed from some complexes (OOX). Groups were cultured with/without oocytes with/without estrogen and then cumulus cell transcriptome analyzed by microarrays.

2013-12-31 | E-GEOD-47967 | biostudies-arrayexpress

BDNF secreted by mesenchymal stem cells improves the quality and development potential of aged oocytes by activating the ERK1/2 signaling pathway

Project description:Decreased oocyte quality is a major determinant of age-associated fertility decline which lacks an effective treatment strategy. The secretome of mesenchymal stem cells (MSC-sec) contains various bioactive factors and has the potential to improve oocyte quality. In this study, MSC-sec treatment significantly increased first polar body emission, improved spindle assembly, reduced aneuploidy rate, and promoted maternal mRNA degradation in aged mouse oocytes, whereas the addition of BDNF antibody blocked the effects of MSC-sec. Furthermore, BDNF treatment alone also improved the oocyte quality from aged mice. Mechanistically, both MSC-sec and BDNF activated the ERK1/2 signaling pathway to increase the expression of DAZL and BTG4 in aged oocytes. Furthermore, injection of MSC-sec or BDNF into aged mouse ovaries significantly improved oocyte quality and early embryonic development. Finally, we demonstrated that BDNF treatment increased both the fertilization rate and blastocyst formation of aged human oocytes. Our study identified BDNF as the functional component of MSC-sec to improve the quality and development potential of aged oocytes by activating the ERK1/2 signaling pathway, suggesting that BDNF has the potential to mitigate age-related decline in oocyte quality.

2025-04-02 | GSE263864 | GEO

Inactivation of Exosc10 in the oocyte impairs oocyte development and maturation, leading to a depletion of the ovarian reserve in mice.

Project description:EXOSC10 is a catalytic subunit of the nuclear RNA exosome with an exoribonuclease activity. The enzyme processes and degrades different classes of RNAs. To delineate the role of EXOSC10 during oocyte growth, specific Exosc10 inactivation was performed in the oocytes from the primordial follicle stage onward using the Gdf9-iCre; Exosc10f/- mouse model (Exosc10cKO(Gdf9)). Exosc10cKO(Gdf9) female mice are infertile. The onset of puberty and the estrus cycle in mutants are initially normal and ovaries contain all follicle classes. By the age of eight weeks, vaginal smears reveal irregular estrus cycles and mutant ovaries display a complete depletion of follicles. Mutant oocytes retrieved from the oviduct are degenerated, sometimes showing an enlarged polar body which may reflect a defective first meiotic division. Under fertilization conditions, the mutant oocytes do not enter into an embryonic development process. Furthermore, we conducted a comparative proteome analysis of wild type and Exosc10 knockout mouse ovaries and identified EXOSC10-dependent proteins involved in many biological processes, such as meiotic cell cycle progression and oocyte maturation. Our results unambiguously demonstrate an essential role for EXOSC10 in oogenesis and may serve as a model for primary ovarian insufficiency in humans.

2023-05-10 | PXD039417 | Pride

Expression data from different stages and types of oocytes and cumulus cells (CCs)

Project description:The bidirectional communication between bovine oocytes and CCs is vital for functioning and development of both cell types. We used microarray to identify genes which are differentially expressed between germinal vesicle (GV)- and metaphase II (MII)-stage oocytes and CCs and those differentially expressed when oocytes mature with or without the other. We also identified genes differentially expressed between CCs at GV and MII stages. Slaughterhouse ovaries were collected and GV-stage cumulus oocyte complexes (COCs) were aspirated. Different stages and types of oocytes and CCs were used for total RNA isolation and hybridisation on Affymetrix microarray.

2010-03-23 | E-GEOD-21005 | biostudies-arrayexpress

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