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      Loss of Ikbkap/Elp1 in mouse oocytes causes spindle disorganization, developmental defects in preimplantation embryos and impaired female fertility

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          Abstract

          Elongator complexes are well known to be involved in a wide variety of cellular processes; however, their functions in mammalian oocytes have not been characterized. Here, we demonstrated in mice that specific deletion of one of the core subunits, Ikbkap/Elp1, in oocytes resulted in spindle defects and chromosome disorganization without affecting folliculogenesis. In accordance with these findings, we observed that Ikbkap mutant female mice are subfertile. Further analyses uncovered that kinetochore–microtubule attachments are severely compromised in Ikbkap-deficient oocytes. Moreover, we revealed that Ikbkap modulates the acetylation status of α-tubulin in oocytes, which may at least in part mediate the meiotic phenotypes described above by affecting microtubule dynamics and kinetochore function. Finally, we showed that embryos derived from Ikbkap-deficient oocytes exhibit an increased frequency of aneuploidy, digyny, progressive delays in preimplantation development, and severe degeneration before reaching the blastocyst stage. In summary, we identify Ikbkap as an important player in regulating oocyte meiosis by modulating tubulin acetylation for chromosome/spindle organization.

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          Author and article information

          Contributors
          fujlin@ntu.edu.tw
          Journal
          Sci Rep
          Sci Rep
          Scientific Reports
          Nature Publishing Group UK (London )
          2045-2322
          11 December 2019
          11 December 2019
          2019
          : 9
          : 18875
          Affiliations
          [1 ]ISNI 0000 0000 9767 1257, GRID grid.412083.c, Department of Animal Science, , National Pingtung University of Science and Technology, ; 91201 Pingtung, Taiwan
          [2 ]ISNI 000000041936754X, GRID grid.38142.3c, Howard Hughes Medical Institute, Harvard Medical School, ; 02115, Boston, USA
          [3 ]ISNI 0000 0004 0378 8438, GRID grid.2515.3, Program in Cellular and Molecular Medicine, , Boston Children’s Hospital, ; Boston, 02115 USA
          [4 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Genetics, , Harvard Medical School, ; Boston, MA 02115 USA
          [5 ]ISNI 000000041936754X, GRID grid.38142.3c, Harvard Stem Cell Institute, , Harvard Medical School, ; Boston, MA 02115 USA
          [6 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Institute of Molecular and Cellular Biology, , National Taiwan University, ; Taipei, 10617 Taiwan
          [7 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Department of Biochemical Science and Technology, , National Taiwan University, ; Taipei, 10617 Taiwan
          [8 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Research Center for Development Biology and Regenerative Medicine, , National Taiwan University, ; Taipei, 10617 Taiwan
          [9 ]Present Address: RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045 Japan
          Author information
          http://orcid.org/0000-0003-4065-0983
          Article
          55090
          10.1038/s41598-019-55090-1
          6906334
          31827135
          42d96fc0-8862-4920-9bc3-5e2c7f6f670a
          © The Author(s) 2019

          Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

          History
          : 30 July 2019
          : 23 November 2019
          Funding
          Funded by: FundRef https://doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan);
          Award ID: NSC 102-2320-B-007 -012 -MY2
          Award Recipient :
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          © The Author(s) 2019

          Uncategorized
          developmental biology,germline development
          Uncategorized
          developmental biology, germline development

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