Viable offspring derived from single unfertilized mammalian oocytes

In mammals, a new life starts with the fusion of an oocyte and asperm cell. Parthenogenesis, a way of generating offspring solelyfrom female gametes, is limited because of problems arising fromgenomic imprinting. Here, we report live mammalian offspringderived from single unfertilized oocytes, which...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 119; no. 12; p. e2115248119
Main Authors Wei, Yanchang, Yang, Cai-Rong, Zhao, Zhen-Ao
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 22.03.2022
Subjects
Animals
Biological Sciences
Demethylation
DNA Methylation
Embryos
Epigenetics
Gametes
Gametocytes
Genomic Imprinting
Mammals
Mammals - genetics
mRNA
Offspring
Oocytes
Oocytes - metabolism
Parthenogenesis
offspring
oocyte
genomic imprinting
early embryo
mammal
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Summary:In mammals, a new life starts with the fusion of an oocyte and asperm cell. Parthenogenesis, a way of generating offspring solelyfrom female gametes, is limited because of problems arising fromgenomic imprinting. Here, we report live mammalian offspringderived from single unfertilized oocytes, which was achieved by tar-geted DNA methylation rewriting of seven imprinting control regions.Oocyte coinjection of catalytically inactive Cas9 (dCas9)-Dnmt3a ordCpf1-Tet1 messenger RNA (mRNA) with single-guide RNAs (sgRNAs)targeting specific regions induced de novo methylation or demethyla-tion, respectively, of the targeted region. Following parthenogeneticactivation, these edited regions showed maintenance of methylationas naturally established regions during early preimplantation develop-ment. The transfer of modified parthenogenetic embryos into fostermothers resulted in significantly extended development andfinally inthe generation of viable full-term offspring. These data demonstratethat parthenogenesis can be achieved by targeted epigenetic rewrit-ing of multiple critical imprinting control regions.
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Edited by Elizabeth Robertson, Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; received August 18, 2021; accepted January 19, 2022
Author contributions: Y.W. designed research; Y.W., C.-R.Y., and Z.-A.Z. performed research; Y.W., C.-R.Y., and Z.-A.Z. contributed new reagents/analytic tools; Y.W., C.-R.Y., and Z.-A.Z. analyzed data; and Y.W. and C.-R.Y. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2115248119