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28 January 2021 Mitochondrial transfer from induced pluripotent stem cells rescues developmental potential of in vitro fertilized embryos from aging females
Chao Zhang, Li Tao, Yuan Yue, Likun Ren, Zhenni Zhang, Xiaodong Wang, Jianhui Tian, Lei An
Author Affiliations +
Abstract

Conventional heterologous mitochondrial replacement therapy is clinically complicated by “triparental” ethical concerns and limited source of healthy donor oocytes or zygotes. Autologous mitochondrial transfer is a promising alternative in rescuing poor oocyte quality and impaired embryo developmental potential associated with mitochondrial disorders, including aging. However, the efficacy and safety of mitochondrial transfer from somatic cells remains largely controversial, and unsatisfying outcomes may be due to distinct mitochondrial state in somatic cells from that in oocytes. Here, we propose a potential strategy for improving in vitro fertilization (IVF) outcomes of aging female patients via mitochondrial transfer from induced pluripotent stem (iPS) cells. Using naturally aging mice and well-established cell lines as models, we found iPS cells and oocytes share similar mitochondrial morphology and functions, whereas the mitochondrial state in differentiated somatic cells is substantially different. By microinjection of isolated mitochondria into fertilized oocytes following IVF, our results indicate that mitochondrial transfer from iPS, but not MEF cells, can rescue the impaired developmental potential of embryos from aging female mice and obtain an enhanced implantation rate following embryo transfer. The beneficial effect may be explained by the fact that mitochondrial transfer from iPS cells not only compensates for aging-associated loss of mtDNA, but also rescues mitochondrial metabolism of subsequent preimplantation embryos. Using mitochondria from iPS cells as the donor, our study not only proposes a promising strategy for improving IVF outcomes of aging females, but also highlights the importance of synchronous mitochondrial state in supporting embryo developmental potential.

Summary Sentence: Induced pluripotent stem cells are more preferred donors for mitochondrial transfer than differentiated somatic cells, for rescuing the impaired developmental potential of IVF embryos from aging females.

Graphical Abstract

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© The Author(s) 2021. 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
Chao Zhang, Li Tao, Yuan Yue, Likun Ren, Zhenni Zhang, Xiaodong Wang, Jianhui Tian, and Lei An "Mitochondrial transfer from induced pluripotent stem cells rescues developmental potential of in vitro fertilized embryos from aging females," Biology of Reproduction 104(5), 1114-1125, (28 January 2021). https://doi.org/10.1093/biolre/ioab009
Received: 9 April 2020; Accepted: 21 January 2021; Published: 28 January 2021
KEYWORDS
aging
embryos
in vitro fertilization
IPS cells
mitochondrial transfer
Oocytes
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