Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice
- Embryotools SL, Spain
- University of Oxford, United Kingdom
- Centre for Genomic Regulation, Spain
- 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
Irene Miguel-Escalada
Maria Garcia-Jiménez
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.
Reviewing Editor
- Martin Pera, The Jackson Laboratory, United States
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.
Version history
- Received: May 20, 2019
- Accepted: April 29, 2020
- Accepted Manuscript published: April 29, 2020 (version 1)
- 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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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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