Cell Stem Cell
Volume 20, Issue 1, 5 January 2017, Pages 112-119
Journal home page for Cell Stem Cell

Short Article
Functional Human Oocytes Generated by Transfer of Polar Body Genomes

https://doi.org/10.1016/j.stem.2016.10.001Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Metaphase II oocytes can be reconstructed by polar body nuclear transfer (PBNT)

  • Reconstructed PBNT oocytes complete meiosis after fertilization with sperm

  • PBNT-derived blastocysts can give rise to phenotypically normal hESC lines

Summary

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.

Keywords

polar body nuclear transfer
meiosis
haploid
reconstructed human oocytes
infertility treatment
mitochondrial replacement therapy

Cited by (0)

8

Co-first author

9

Lead Contact