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

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): Homo sapiens

PROVIDER: GSE175832 | 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 oocyte]

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 | GSE175835 | GEO

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

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 [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

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

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

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. Oocytes were derived from the ovary of young (6-8 week-old) C57BL/6 mice and aged (41-43 week-old) mice and pooled according to whether they were 20 to 50 um or 60 to 80 um in diameter. Of oocytes with the diameter of more than 60um, oocyte from young mice are called ‘young oocytes’ and those from aged mice near the end of their reproductive life span are called ‘aged oocytes’ to analyze the miRNA profiling associated with aging. They were also each called ‘small oocytes’ or ‘large oocytes’ from the size of 60um so as to investigate miRNA profiling associated with growing. Total RNA from oocytes was isolated using mirVana miRNA Isolation Kit (Applied Biosystems). MiRNA expression was profiled using Agilent's Mouse miRNA Microarray Kit (G4472A) annotated against the Sanger miRBASE 10.1 database of miRNAs. This miRNA microarray was provided by Agilent Technologies (Santa Clara, CA). Each sample was run in duplicate.

2012-09-04 | E-GEOD-17966 | biostudies-arrayexpress

Growth hormone supplementation reduces aneuploidy and improves the quality of oocytes by activating ERK1/2 pathway in aged mice

Project description:The decline in oocyte quality is a limiting factor of female fertility; however, strategies to maintain the oocyte quality of aged women are not available. In this study, we showed that growth hormone (GH) supplementation in vivo not only alleviated the decline in oocyte number caused by aging, but also improved the quality and developmental potential of aged oocytes. Strikingly, GH supplementation reduced aneuploidy in aged oocytes. Proteomic analysis indicated that the ERK1/2 pathway was involved in the reduction in aneuploidy rate of aged oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 might be involved in the regulation of ERK1/2 by GH in aged oocytes. Collectively, our findings revealed that GH supplementation protects oocytes from aging-related aneuploidy and enhances the quality of aged oocytes, and could be used to improve the outcome of assisted reproduction in aged women.

2023-07-20 | PXD039147 | Pride

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