Role of miRNAs in glucose metabolism of mouse cumulus cells†.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0207224 Publication Model: Print Cited Medium: Internet ISSN: 1529-7268 (Electronic) Linking ISSN: 00063363 NLM ISO Abbreviation: Biol Reprod Subsets: MEDLINE
    • Publication Information:
      Publication: 2017- : New York : Oxford University Press
      Original Publication: Champaign, Ill. : Society for the Study of Reproduction
    • Subject Terms:
      Cumulus Cells*/metabolism ; MicroRNAs*/metabolism ; MicroRNAs*/genetics ; Glucose*/metabolism ; Glycolysis*/physiology; Animals ; Mice ; Female ; Pentose Phosphate Pathway ; Oocytes/metabolism
    • Abstract:
      It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: [email protected].)
    • Grant Information:
      31772599 China National Natural Science Foundation; ZR2022MC036 Natural Science Foundation of Shandong Province
    • Contributed Indexing:
      Keywords: cumulus cells; glycolysis; miRNAs; oocyte maturation; pentose phosphate pathway
    • Publication Date:
      Date Created: 20240124 Date Completed: 20240515 Latest Revision: 20240515
    • Publication Date:
      20240515
    • Accession Number:
      10.1093/biolre/ioae013
    • Accession Number:
      38267362