Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-04-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/48591 |
| _version_ | 1828384643980722176 |
|---|---|
| author | Nuno Costa-Borges Katharina Spath Irene Miguel-Escalada Enric Mestres Rosa Balmaseda Anna Serafín Maria Garcia-Jiménez Ivette Vanrell Jesús González Klaus Rink Dagan Wells Gloria Calderón |
| author_facet | Nuno Costa-Borges Katharina Spath Irene Miguel-Escalada Enric Mestres Rosa Balmaseda Anna Serafín Maria Garcia-Jiménez Ivette Vanrell Jesús González Klaus Rink Dagan Wells Gloria Calderón |
| author_sort | Nuno Costa-Borges |
| collection | DOAJ |
| description | 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 five 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. |
| first_indexed | 2024-12-10T05:05:43Z |
| format | Article |
| id | doaj.art-f843ab1de4354b3eaeac8a70e16c467d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:05:43Z |
| publishDate | 2020-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f843ab1de4354b3eaeac8a70e16c467d2022-12-22T02:01:15ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.48591Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in miceNuno Costa-Borges0https://orcid.org/0000-0002-2073-7515Katharina Spath1Irene Miguel-Escalada2https://orcid.org/0000-0003-3461-6404Enric Mestres3https://orcid.org/0000-0001-6140-6416Rosa Balmaseda4Anna Serafín5Maria Garcia-Jiménez6https://orcid.org/0000-0003-3321-8869Ivette Vanrell7Jesús González8Klaus Rink9Dagan Wells10Gloria Calderón11https://orcid.org/0000-0003-3235-0323Embryotools, Parc Cientific de Barcelona, Barcelona, SpainNuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom; Juno Genetics, Winchester House, Oxford Science Park, Oxford, United KingdomGenomics and Bioinformatics, Centre for Genomic Regulation, Barcelona, SpainEmbryotools, Parc Cientific de Barcelona, Barcelona, SpainPCB Animal Facility, Parc Cientific de Barcelona, Barcelona, SpainPCB Animal Facility, Parc Cientific de Barcelona, Barcelona, SpainEmbryotools, Parc Cientific de Barcelona, Barcelona, SpainEmbryotools, Parc Cientific de Barcelona, Barcelona, SpainPCB Animal Facility, Parc Cientific de Barcelona, Barcelona, SpainEmbryotools, Parc Cientific de Barcelona, Barcelona, SpainNuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom; Juno Genetics, Winchester House, Oxford Science Park, Oxford, United KingdomEmbryotools, Parc Cientific de Barcelona, Barcelona, SpainThe 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 five 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.https://elifesciences.org/articles/48591InfertilitySpindle transferoocytesmitochondrial DNAheteroplasmyembryo development |
| spellingShingle | Nuno Costa-Borges Katharina Spath Irene Miguel-Escalada Enric Mestres Rosa Balmaseda Anna Serafín Maria Garcia-Jiménez Ivette Vanrell Jesús González Klaus Rink Dagan Wells Gloria Calderón Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice eLife Infertility Spindle transfer oocytes mitochondrial DNA heteroplasmy embryo development |
| title | Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice |
| title_full | Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice |
| title_fullStr | Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice |
| title_full_unstemmed | Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice |
| title_short | Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice |
| title_sort | maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice |
| topic | Infertility Spindle transfer oocytes mitochondrial DNA heteroplasmy embryo development |
| url | https://elifesciences.org/articles/48591 |
| work_keys_str_mv | AT nunocostaborges maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT katharinaspath maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT irenemiguelescalada maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT enricmestres maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT rosabalmaseda maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT annaserafin maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT mariagarciajimenez maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT ivettevanrell maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT jesusgonzalez maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT klausrink maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT daganwells maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice AT gloriacalderon maternalspindletransferovercomesembryodevelopmentalarrestcausedbyooplasmicdefectsinmice |