Functional Human Oocytes Generated by Transfer of Polar Body Genomes

Hong Ma, Ryan C. O'Neil, Nuria Marti Gutierrez, Manoj Hariharan, Zhuzhu Z. Zhang, Yupeng He, Cengiz Cinnioglu, Refik Kayali, Eunju Kang, Yeonmi Lee, Tomonari Hayama, Amy Koski, Joseph Nery, Rosa Castanon, Rebecca Tippner-Hedges, Riffat Ahmed, Crystal Van Dyken, Ying Li, Susan Olson, David BattagliaDavid M. Lee, Diana H. Wu, Paula Amato, Don P. Wolf, Joseph R. Ecker, Shoukhrat Mitalipov

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalCell Stem Cell
Volume20
Issue number1
DOIs
StatePublished - Jan 5 2017

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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  • Cite this

    Ma, H., O'Neil, R. C., Marti Gutierrez, N., Hariharan, M., Zhang, Z. Z., He, Y., Cinnioglu, C., Kayali, R., Kang, E., Lee, Y., Hayama, T., Koski, A., Nery, J., Castanon, R., Tippner-Hedges, R., Ahmed, R., Van Dyken, C., Li, Y., Olson, S., ... Mitalipov, S. (2017). Functional Human Oocytes Generated by Transfer of Polar Body Genomes. Cell Stem Cell, 20(1), 112-119. https://doi.org/10.1016/j.stem.2016.10.001