ArticleOncotarget2015
DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3'-end GC density.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 77 citations in OpenAlex.
- Bioengineering Ovarian Endocrine Function: From Follicle Modeling to Cell-Based Hormone Therapy.Advanced healthcare materials · 2026Review
- Mapping ovarian cellular and molecular landscape across the lifespan of women: a scoping review.Human reproduction update · 2026Article
- DNMT/TET Imbalance and Network-Level DNA Methylation Remodeling in Ovarian Aging: Mechanistic Perspectives.Biology · 2026Review
- Epigenetic regulation by DNA methylation in PCOS and POI: mechanisms of ovarian dysfunction and implications for clinical research.Journal of ovarian research · 2026Review
- Dynamic Changes of Selected Signaling Molecules in Ovaries Following Early-Life Exposure to Fumonisin B1 in Wistar Rats in Association With DNA Methylation.Physiological research · 2025Article
- Epigenomic Landscape of Human Cumulus Cells in Premature Ovarian Insufficiency Using Single-Base Resolution Methylome and Hydroxymethylome.Journal of cellular and molecular medicine · 2024Article
- Review
- Conservative Hypomethylation of Mesenchymal Stem Cells and Their Secretome Restored the Follicular Development in Cisplatin-Induced Premature Ovarian Failure Mice.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- DNA methylation as a window into female reproductive aging.Epigenomics · 2024Review
- A DNA Methylation Perspective on Infertility.Genes · 2023Review
- Paxillin knockout in mouse granulosa cells increases fecundity†.Biology of reproduction · 2023Article
- The Role of Advanced Parental Age in Reproductive Genetics.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Pathomechanisms of Prenatally Programmed Adult Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- DNA methylation abnormalities induced by advanced maternal age in villi prime a high-risk state for spontaneous abortion.Clinical epigenetics · 2023Article
- The Role of L-Arginine-NO System in Female Reproduction: A Narrative Review.International journal of molecular sciences · 2022Review
- The process of ovarian aging: it is not just about oocytes and granulosa cells.Journal of assisted reproduction and genetics · 2022Review
- Epigenetic regulation in premature ovarian failure: A literature review.Frontiers in physiology · 2022Review
- Dnmt3aa but Not Dnmt3ab Is Required for Maintenance of Gametogenesis in Nile Tilapia (International journal of molecular sciences · 2021Article
- Article
- Molecular characterisation of ILRUN, a novel inhibitor of proinflammatory and antimicrobial cytokines.Heliyon · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Diminished ovarian function occurs early and is a primary cause for age-related decline in female fertility; however, its underlying mechanism remains unclear. This study investigated the roles that genome and epigenome structure play in age-related changes in gene expression and ovarian function, using human ovarian granulosa cells as an experimental system. DNA methylomes were compared between two groups of women with distinct age-related differences in ovarian functions, using both Methylated DNA Capture followed by Next Generation Sequencing (MethylCap-seq) and Reduced Representation Bisulfite Sequencing (RRBS); their transcriptomes were investigated using mRNA-seq. Significant, non-random changes in transcriptome and DNA methylome features are observed in human ovarian granulosa cells as women age and their ovarian functions deteriorate. The strongest correlations between methylation and the age-related changes in gene expression are not confined to the promoter region; rather, high densities of hypomethylated CpG-rich regions spanning the gene body are preferentially associated with gene down-regulation. This association is further enhanced where CpG regions are localized near the 3'-end of the gene. Such features characterize several genes crucial in age-related decline in ovarian function, most notably the AMH (Anti-Müllerian Hormone) gene. The genome-wide correlation between the density of hypomethylated intragenic and 3'-end regions and gene expression suggests previously unexplored mechanisms linking epigenome structure to age-related physiology and pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.