Cumulus Cells Block Oocyte Meiotic Resumption via Gap Junctions in Cumulus Oocyte Complexes Subjected to DNA Double-Strand Breaks.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Cumulus Cells/*metabolism ; DNA/*metabolism ; Oocytes/*metabolism; Adenylyl Cyclases/genetics ; Adenylyl Cyclases/metabolism ; Animals ; Carbenoxolone/pharmacology ; Cumulus Cells/cytology ; Cyclic AMP/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 3/genetics ; Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism ; DNA/chemistry ; DNA Breaks, Double-Stranded/drug effects ; Female ; Gap Junctions/metabolism ; Gene Expression Regulation/drug effects ; Histones/metabolism ; Meiosis/drug effects ; Metaphase ; Mice, Inbred ICR ; Oocytes/cytology ; Oocytes/drug effects ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism
    • Abstract:
      During mammalian oocyte growth, genomic DNA may accumulate DNA double-strand breaks (DSBs) induced by factors such as reactive oxygen species. Recent evidence demonstrated that slight DSBs do not activate DNA damage checkpoint proteins in denuded oocytes. These oocytes, even with DNA DSBs, can resume meiosis and progress to metaphase of meiosis II. Meiotic resumption in oocytes is also controlled by the surrounding cumulus cells; accordingly, we analyzed whether cumulus-cell enclosed oocytes (CEOs) with DNA damage are able to resume meiosis. Compared with DNA-damaged denuded oocytes, we found that meiotic resumption rates of CEOs significantly decreased. To assess the mechanism by which cumulus cells block meiotic resumption in CEOs with DNA DSBs, we treated the cumulus oocyte complex with the gap junction inhibitor carbenoxolone and found that carbenoxolone can rescue the block in CEO meiosis induced by DNA DSBs. Since cumulus cell-synthesized cAMPs can pass through the gap junctions between oocyte and cumulus cell to block oocyte meiosis, we measured the expression levels of adenylate cyclase 1 (Adcy1) in cumulus cells, and G-protein coupled receptor 3 (Gpr3) and phosphodiesterase 3A (Pde3a) in oocytes, and found that the mRNA expression level of Adcy1 increased significantly in DNA-damaged cumulus cells. In conclusion, our results indicate that DNA DSBs promote cAMP synthesis in cumulus cells, and cumulus cAMPs can inhibit meiotic resumption of CEOs through gap junctions.
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    • Accession Number:
      0 (GPR3 protein, mouse)
      0 (H2AX protein, mouse)
      0 (Histones)
      0 (RNA, Messenger)
      0 (Receptors, G-Protein-Coupled)
      9007-49-2 (DNA)
      E0399OZS9N (Cyclic AMP)
      EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
      EC 3.1.4.17 (Pde3a protein, mouse)
      EC 4.6.1.1 (Adenylyl Cyclases)
      EC 4.6.1.1 (adenylyl cyclase 1)
      MM6384NG73 (Carbenoxolone)
    • Publication Date:
      Date Created: 20151118 Date Completed: 20160628 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC4648486
    • Accession Number:
      10.1371/journal.pone.0143223
    • Accession Number:
      26575642