Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HEP14 treatment improves ovarian function in aged mice through mitophagy enhancement and oxidative stress reducton

ABSTRACT: Ovarian senescence impacts reproductive health and accelerates the overall aging process. Despite extensive research in this area there is still a dearth of effective therapeutic strategies. We here report the rejuvenating effects of HEP14, a natural activator of PKC pathway, on aged ovarian function. Further, we detail a method to fabricate HEP14-loaded PLGA microspheres designed for controlled and sustained drug release in vivo. Transcriptomic analysis revealed a significant overlap between the transcriptional profiles of HEP14-treated aged ovaries and those of adult ovaries, suggesting molecular rejuvenation process. Histopathological evaluations following treatment demonstrated that HEP14 not only enhances mitophagy but also exhibits antioxidative properties and promotes follicular regeneration. As a result, ovarian endocrine function was ultimately restored in aged mice, evident in raised serum levels of E2, AMH, Inhibin A/B and lowered FSH levels. In vitro studies further showcased restorative effect of HEP14 on enhancement of mitophagy and mitochondrial function by the activation of the PKC-ERK1/2 pathway in senescent GCs, which are integral to the action mechanism of HEP14. These findings pave the way for new therapeutic approaches for developing therapeutic strategies aimed at improving reproductive health in aging individuals.

ORGANISM(S): Mus musculus

PROVIDER: GSE273724 | GEO | 2025/07/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Polyamine metabolite spermidine rejuvenates the oocyte quality by enhancing mitophagy during female reproductive aging

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

Inflammatory Bowel Disease Leads to Long-Term Ovarian Dysfunction via Immune-Mediated Follicular Aging

Project description:The rising global incidence of inflammatory bowel disease (IBD) is associated with reduced levels of anti-Müllerian hormone (AMH), a key biomarker for premature ovarian insufficiency (POI), highlighting reproductive risks for women of childbearing age. To investigate the connection between IBD and ovarian aging, we used a dextran sodium sulfate (DSS)-induced mouse model of IBD and assessed reproductive outcomes, including ovarian reserve, folliculogenesis, hormone profiles, and estrous cyclicity. Transcriptomic analysis of ovarian tissue showed that IBD upregulates genes associated with aging. Gene Ontology enrichment pointed to signaling pathways involved in cellular senescence, oxidative stress response, and senescence-associated secretory phenotypes. By integrating our ovarian transcriptomic data with single-cell RNA-seq datasets from young (3-month) and aged (9-month) mouse ovaries, we found significant parallels between IBD-induced transcriptional changes and natural ovarian aging. Flow cytometry confirmed elevated levels of T cells, CD8+ T cells, and macrophages in the ovaries, indicating localized immune activation. Similar systemic immune changes were observed in peripheral blood mononuclear cells, with expanded T cell and macrophage populations. TUNEL assays and qPCR further validated accelerated ovarian aging in IBD mice, showing increased granulosa cell apoptosis and upregulated aging-related markers. Notably, even after an 89-day recovery period following DSS treatment, persistent deficits in follicular counts, hormonal balance, and estrous regularity indicated irreversible ovarian dysfunction. Our findings demonstrate that IBD triggers ovarian inflammation, depletes ovarian reserve, and accelerates aging processes, leading to long-term reproductive impairment. This study elucidates the mechanistic links between IBD and POI, providing insights for therapeutic strategies to mitigate fertility risks in affected women.

2025-02-17 | GSE289404 | GEO

Transcriptional profiling by array of ovaries from aged mice

Project description:We transcriptionally profiled ovaries harvested from young and middle-aged outbred CD1 mice to elucidate mechanisms and identify novel markers of ovarian aging.

2018-12-15 | E-MTAB-7493 | biostudies-arrayexpress

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 [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

Single-Cell Transcriptomic Atlas of Primate Ovarian Aging

Project description:Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species and apoptosis were observed in granulosa cells from aged women. This study provides comprehensive understanding of the cell type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.

2020-01-28 | GSE130664 | GEO

Single cell RNA sequencing reveals the aging associated change of ovarian macrophage populations

Project description:Macrophages are important modulators of the ovarian tissue microenvironment, and are associated with the ovarian aging process. To dissect the changes of macrophages during ovarian aging, we used a combination of single cell RNA sequencing (scRNAseq) and flow cytometry to inspect the CD45+ CD11b+ myeloid cells in young (3 months old) and aged (15 months old) murine ovaries, which mainly consists of macrophages, monocytes and dendritic cells.

2025-05-31 | GSE236712 | 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