Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice

  1. Nuno Costa-Borges  Is a corresponding author
  2. Katharina Spath
  3. Irene Miguel-Escalada
  4. Enric Mestres
  5. Rosa Balmaseda
  6. Anna Serafín
  7. Maria Garcia-Jiménez
  8. Ivette Vanrell
  9. Jesús González
  10. Klaus Rink
  11. Dagan Wells
  12. Gloria Calderón
  1. Embryotools SL, Spain
  2. University of Oxford, United Kingdom
  3. Centre for Genomic Regulation, Spain
  4. Parc Cientific de Barcelona, Spain

Abstract

The developmental potential of early embryos is mainly dictated by the quality of the oocyte. Here, we explore the utility of the maternal spindle transfer (MST) technique as a reproductive approach to enhance oocyte developmental competence. Our proof-of-concept experiments show that replacement of the entire cytoplasm of oocytes from a sensitive mouse strain overcomes massive embryo developmental arrest characteristic of non-manipulated oocytes. Genetic analysis confirmed minimal carryover of mtDNA following MST. Resulting mice showed low heteroplasmy levels in multiple organs at adult age, normal histology and fertility. Mice were followed for 5 generations (F5), revealing that heteroplasmy was reduced in F2 mice and was undetectable in the subsequent generations. This pre-clinical model demonstrates the high efficiency and potential of the MST technique, not only to prevent the transmission of mtDNA mutations, but also as a new potential treatment for patients with certain forms of infertility refractory to current clinical strategies.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Nuno Costa-Borges

    R&D Department, Embryotools SL, Barcelona, Spain
    For correspondence
    nuno.borges@embryotools.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2073-7515
  2. Katharina Spath

    Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Irene Miguel-Escalada

    Genomics and Bioinformatics, Centre for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3461-6404
  4. Enric Mestres

    R&D Department, Embryotools SL, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6140-6416
  5. Rosa Balmaseda

    Animal's Alliance Facility, Parc Cientific de Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Anna Serafín

    Animal's Alliance Facility, Parc Cientific de Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Maria Garcia-Jiménez

    R&D Department, Embryotools SL, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3321-8869
  8. Ivette Vanrell

    R&D Department, Embryotools SL, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Jesús González

    Animal's Alliance Facility, Parc Cientific de Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Klaus Rink

    R&D Department, Embryotools SL, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  11. Dagan Wells

    Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Gloria Calderón

    R&D Department, Embryotools SL, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3235-0323

Funding

European Regional Development Fund (RD-15-1-0011)

  • Nuno Costa-Borges

National Institutes of Health (1R01HD092550-01)

  • Dagan Wells

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal care and procedures were conducted according to protocols approved by the Ethics Committee on Animal Research (DAMM-7436) of the Parc Cientific of Barcelona (PCB), Spain.

Reviewing Editor

  1. Martin Pera, The Jackson Laboratory, United States

Version history

  1. Received: May 20, 2019
  2. Accepted: April 29, 2020
  3. Accepted Manuscript published: April 29, 2020 (version 1)
  4. Version of Record published: May 29, 2020 (version 2)

Copyright

© 2020, Costa-Borges et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nuno Costa-Borges
  2. Katharina Spath
  3. Irene Miguel-Escalada
  4. Enric Mestres
  5. Rosa Balmaseda
  6. Anna Serafín
  7. Maria Garcia-Jiménez
  8. Ivette Vanrell
  9. Jesús González
  10. Klaus Rink
  11. Dagan Wells
  12. Gloria Calderón
(2020)
Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice
eLife 9:e48591.
https://doi.org/10.7554/eLife.48591

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