Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27268410", "kind": "science-record", "revision": 2, "content_hash": "sha256:b8a6f3346917babb6c96b81ccc65b4109f53cba9f383ade71e537b9d60d7182f", "created_at": "2026-11-01T15:40:18Z", "updated_at": "2026-11-01T18:48:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.", "doi": "10.1093/molehr/gaw038", "pmid": "27268410", "authors": ["E Molinari", "H Bar", "A M Pyle", "P Patrizio"], "journal": "Molecular human reproduction", "year": 2016, "abstract": "STUDY QUESTION: Can RNA sequencing of human cumulus cells (CC) reveal molecular pathways involved in the physiology of reproductive aging?\nSTUDY FINDING: Senescent but not young CC activate gene pathways associated with hypoxia and oxidative stress.\nWHAT IS KNOWN ALREADY: Shifts in socioeconomic norms are resulting in larger numbers of women postponing childbearing. The reproductive potential is sharply decreased with aging, and the reasons are poorly understood. Since CCs play an integral role in oocyte maturation and direct access to human oocytes is limited, we used whole transcriptome analysis of these somatic cells to gain insights into the molecular mechanisms playing a role in follicular senescence.\nSTUDY DESIGN, SAMPLES/MATERIALS, METHODS: Twenty CC samples (from a total of 15 patients) were obtained from oocytes of either male factor or egg donor patients. RNA sequencing and bioinformatic tools were used to identify differentially expressed genes between CCs from seven aged and eight young patients (<35 (years old) y.o. vs >40 y.o.). Quantitative-PCR and immunoflourescent staining were used for validation.\nMAIN RESULTS AND THE ROLE OF CHANCE: RNA sequencing identified 11 572 genes expressed in CC of both age cohorts, 45 of which were differentially expressed. In CC collected from patients >40 y.o., genes involved in the hypoxia stress response (NOS2, RORA and NR4A3), vasculature development (NR2F2, PTHLH), glycolysis (RALGAPA2 and TBC1D4) and cAMP turnover (PDE4D) were significantly overexpressed when compared with CC of patients younger than 35 y.o.\nLIMITATIONS, REASONS FOR CAUTION: This study focused almost exclusively on assessing the genetic differences in CC transcriptome between young and older women. These genetic findings were not fully correlated with embryonic development and clinical outcome.\nWIDER IMPLICATIONS OF THE FINDINGS: Our data provide a new hypothesis-follicular hypoxia-as the main mechanism leading to ovarian follicular senescence and suggest a link between cumulus cell aging and oocyte quality decay. If specific molecular findings of hypoxia would be confirmed also in oocytes, genetic platforms could screen CC for hypoxic damage and identify healthier oocytes. Protocols of ovarian stimulation in older patients could also be adjusted to diminish oocyte exposure time to hypoxic follicles.\nLARGE SCALE DATA: GEO accession number: GSE81579 STUDY FUNDING AND COMPETING INTERESTS: Funded in part by EMD Serono Grant for Fertility Innovation (GFI).", "claims": [{"id": "claim-target-result", "statement": "RNA sequencing and bioinformatic tools were used to identify differentially expressed genes between cumulus-cell samples from aged and young patients; the source data are available under GEO accession GSE81579. 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