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Chapter 14 - Germline Nuclear Transfer Technology to Overcome Mitochondrial Diseases and Female Infertility

Published online by Cambridge University Press:  02 December 2021

By
Mao-Xing Tang ,
Annekatrien Boel ,
Paul Couke  and
Björn Heindryckx
Edited by
Gianpiero D. Palermo  and
Zsolt Peter Nagy
Gianpiero D. Palermo
Affiliation:
Cornell Institute of Reproductive Medicine, New York
Zsolt Peter Nagy
Affiliation:
Reproductive Biology Associates, Atlanta, GA
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Summary

Mitochondrial (mt)DNA mutations can cause a broad range of severely debilitating or fatal disorders. There is no cure available and the only available treatments have purely symptomatic effects. Preventing mitochondrial disease transmission is therefore a major priority. Germline nuclear transfer (NT), such as maternal spindle (ST), pronuclear (PNT) or polar body (PBT) transfer, has been proposed as a possible strategy to prevent mother-to-child transmission of mtDNA mutations. This technology involves nuclear genome transfer from an oocyte or zygote carrying mtDNA mutations to an enucleated donor counterpart with healthy mtDNA. In addition, the technology has also been considered as a treatment option for certain infertility indications, such as women experiencing poor embryo development, with the expectation of improving in vitro treatment outcomes. Here, we provide an overview on recent developments in the field of NT, either with the aim to avoid mtDNA diseases or to overcome certain forms of female infertility.

Keywords

germline nuclear transfermitochondrial diseasesinfertilitymitochondrial DNAembryo development
Type
Chapter
Information
Manual of Intracytoplasmic Sperm Injection in Human Assisted Reproduction
With Other Advanced Micromanipulation Techniques to Edit the Genetic and Cytoplasmic Content of the Oocyte
 , pp. 141 - 147
Publisher: Cambridge University Press
Print publication year: 2021

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References

Craven, L, Tang, MX, Gorman, GS, De Sutter, P, Heindryckx, B. Novel reproductive technologies to prevent mitochondrial disease. Hum Reprod Update 2017; 23(5): 501–19.CrossRefGoogle ScholarPubMed
Neupane, J, Ghimire, S, Vandewoestyne, M, et al. Cellular heterogeneity in the level of mtDNA heteroplasmy in mouse embryonic stem cells. Cell Rep 2015; 13(7): 1304–9.CrossRefGoogle ScholarPubMed
Tachibana, M, Sparman, M, Sritanaudomchai, H, et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature 2009; 461(7262): 367–72.CrossRefGoogle ScholarPubMed
Tachibana, M, Amato, P, Sparman, M, et al. Towards germline gene therapy of inherited mitochondrial diseases. Nature 2013; 493(7434): 627–31.CrossRefGoogle ScholarPubMed
Paull, D, Emmanuele, V, Weiss, KA, et al. Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants. Nature 2013; 493(7434): 632–7.CrossRefGoogle ScholarPubMed
Yamada, M, Emmanuele, V, Sanchez-Quintero, MJ, et al. Genetic drift can compromise mitochondrial replacement by nuclear transfer in human oocytes. Cell Stem Cell 2016; 18(6): 749–54.Google Scholar
Kang, E, Wu, J, Gutierrez, NM, et al. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature 2016; 540(7632): 270–5.CrossRefGoogle ScholarPubMed
Zhang, J, Liu, H, Luo, S, et al. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online 2017; 34(4): 361–8.CrossRefGoogle ScholarPubMed
Sato, A, Kono, T, Nakada, K, et al. Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear transplantation. Proc Natl Acad Sci USA 2005; 102(46): 16765–70.CrossRefGoogle ScholarPubMed
Neupane, J, Vandewoestyne, M, Ghimire, S, et al. Assessment of nuclear transfer techniques to prevent the transmission of heritable mitochondrial disorders without compromising embryonic development competence in mice. Mitochondrion 2014; 18: 27–33.Google Scholar
Craven, L, Tuppen, HA, Greggains, GD, et al. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 2010; 465(7294): 82–9.CrossRefGoogle ScholarPubMed
Hyslop, LA, Blakeley, P, Craven, L, et al. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature 2016; 534(7607): 383–6.Google Scholar
Wu, K, Chen, T, Huang, S, et al. Mitochondrial replacement by pre-pronuclear transfer in human embryos. Cell Res 2017; 27(6): 834–7.Google Scholar
Wang, T, Sha, H, Ji, D, et al. Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases. Cell 2014; 157(7): 1591–604.Google Scholar
Ma, H, O’Neil, RC, Marti Gutierrez, N, et al. Functional human oocytes generated by transfer of polar body genomes. Cell Stem Cell 2017; 20(1): 112–9.Google Scholar
Wu, K, Zhong, C, Chen, T, et al. Polar bodies are efficient donors for reconstruction of human embryos for potential mitochondrial replacement therapy. Cell Res 2017; 27(8): 1069–72.Google Scholar
Tang, M, Guggilla, RR, Gansemans, Y, et al. Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants. Mol Hum Reprod 2019; 25(12): 797–810.Google Scholar
Wei, W, Tuna, S, Keogh, MJ, et al. Germline selection shapes human mitochondrial DNA diversity. Science 2019; 364(6442).Google Scholar
Eyre-Walker, A. Mitochondrial replacement therapy: are mito-nuclear interactions likely to be a problem? Genetics 2017; 205(4): 1365–72.CrossRefGoogle ScholarPubMed
Dobler, R, Dowling, DK, Morrow, EH, Reinhardt, K. A systematic review and meta-analysis reveals pervasive effects of germline mitochondrial replacement on components of health. Hum Reprod Update 2018; 24(5): 519–34.CrossRefGoogle ScholarPubMed
Rishishwar, L, Jordan, IK. Implications of human evolution and admixture for mitochondrial replacement therapy. BMC Genomics 2017; 18(1): 140.CrossRefGoogle ScholarPubMed
Zhang, J, Zhuang, GL, Zeng, Y, et al. Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF. Reprod Biomed Online 2016; 33(4): 529–33.Google Scholar
Labarta, E, de Los Santos, MJ, Herraiz, S, et al. Autologous mitochondrial transfer as a complementary technique to intracytoplasmic sperm injection to improve embryo quality in patients undergoing in vitro fertilization-a randomized pilot study. Fertil Steril 2019; 111(1): 86–96.CrossRefGoogle ScholarPubMed

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