BioOne.org will be down briefly for maintenance on 17 December 2024 between 18:00-22:00 Pacific Time US. We apologize for any inconvenience.
How to translate text using browser tools
17 October 2019 Deleterious mtDNA mutations are common in mature oocytes
Hong Ma, Tomonari Hayama, Crystal Van Dyken, Hayley Darby, Amy Koski, Yeonmi Lee, Nuria Marti Gutierrez, Satsuki Yamada, Ying Li, Michael Andrews, Riffat Ahmed, Dan Liang, Thanasup Gonmanee, Eunju Kang, Mohammed Nasser, Beth Kempton, John Brigande, Trevor J. McGill, Andre Terzic, Paula Amato, Shoukhrat Mitalipov
Author Affiliations +
Abstract

Heritable mitochondrial DNA (mtDNA) mutations are common, yet only a few recurring pathogenic mtDNA variants account for the majority of known familial cases in humans. Purifying selection in the female germline is thought to be responsible for the elimination of most harmful mtDNA mutations during oogenesis. Here we show that deleterious mtDNA mutations are abundant in ovulated mature mouse oocytes and preimplantation embryos recovered from PolG mutator females but not in their live offspring. This implies that purifying selection acts not in the maternal germline per se, but during post-implantation development. We further show that oocyte mtDNA mutations can be captured and stably maintained in embryonic stem cells and then reintroduced into chimeras, thereby allowing examination of the effects of specific mutations on fetal and postnatal development.

Summary sentence

Our studies show that high heteroplasmy deleterious mtDNA mutations presenting in mature mouse oocytes are eliminated during post-implantation development. The occurrence of purifying selection against deleterious mtDNA mutations during fetal development plays an important role in preventing the accumulation of pathogenic mutations that would cause consequences to species survival.

© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Hong Ma, Tomonari Hayama, Crystal Van Dyken, Hayley Darby, Amy Koski, Yeonmi Lee, Nuria Marti Gutierrez, Satsuki Yamada, Ying Li, Michael Andrews, Riffat Ahmed, Dan Liang, Thanasup Gonmanee, Eunju Kang, Mohammed Nasser, Beth Kempton, John Brigande, Trevor J. McGill, Andre Terzic, Paula Amato, and Shoukhrat Mitalipov "Deleterious mtDNA mutations are common in mature oocytes," Biology of Reproduction 102(3), 607-619, (17 October 2019). https://doi.org/10.1093/biolre/ioz202
Received: 8 August 2019; Accepted: 15 October 2019; Published: 17 October 2019
KEYWORDS
mitochondria
mtDNA
oocyte
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top