| Literature DB >> 27840020 |
Hong Ma1, Ryan C O'Neil2, Nuria Marti Gutierrez1, Manoj Hariharan3, Zhuzhu Z Zhang3, Yupeng He2, Cengiz Cinnioglu4, Refik Kayali4, Eunju Kang1, Yeonmi Lee1, Tomonari Hayama1, Amy Koski1, Joseph Nery3, Rosa Castanon3, Rebecca Tippner-Hedges1, Riffat Ahmed1, Crystal Van Dyken1, Ying Li1, Susan Olson5, David Battaglia6, David M Lee6, Diana H Wu6, Paula Amato6, Don P Wolf1, Joseph R Ecker7, Shoukhrat Mitalipov8.
Abstract
Oocyte defects lie at the heart of some forms of infertility and could potentially be addressed therapeutically by alternative routes for oocyte formation. Here, we describe the generation of functional human oocytes following nuclear transfer of first polar body (PB1) genomes from metaphase II (MII) oocytes into enucleated donor MII cytoplasm (PBNT). The reconstructed oocytes supported the formation of de novo meiotic spindles and, after fertilization with sperm, meiosis completion and formation of normal diploid zygotes. While PBNT zygotes developed to blastocysts less frequently (42%) than controls (75%), genome-wide genetic, epigenetic, and transcriptional analyses of PBNT and control ESCs indicated comparable numbers of structural variations and markedly similar DNA methylation and transcriptome profiles. We conclude that rescue of PB1 genetic material via introduction into donor cytoplasm may offer a source of oocytes for infertility treatment or mitochondrial replacement therapy for mtDNA disease.Entities:
Keywords: haploid; infertility treatment; meiosis; mitochondrial replacement therapy; polar body nuclear transfer; reconstructed human oocytes
Mesh：
Year: 2016 PMID： 27840020 PMCID： PMC5218919 DOI： 10.1016/j.stem.2016.10.001
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633