Functional Human Oocytes Generated by Transfer of Polar Body Genomes

Cell Stem Cell. 2017 Jan 5;20(1):112-119. doi: 10.1016/j.stem.2016.10.001. Epub 2016 Nov 10.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blastocyst / metabolism
  • DNA Methylation / genetics
  • Embryonic Development / genetics
  • Epigenesis, Genetic
  • Female
  • Fertilization in Vitro
  • Gene Expression Profiling
  • Genome, Human*
  • Genomic Instability
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Male
  • Metaphase
  • Nuclear Transfer Techniques*
  • Oocytes / metabolism*
  • Ploidies
  • Polar Bodies / metabolism*
  • Sequence Analysis, RNA
  • Spermatozoa / metabolism
  • Spindle Apparatus / metabolism
  • Transcription, Genetic