Format

Send to

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

Functional Human Oocytes Generated by Transfer of Polar Body Genomes.

Author information

1
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
2
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Bioinformatics Program, University of California at San Diego, La Jolla, CA 92093, USA.
3
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
IviGen Los Angeles, Torrance, CA 90501, USA.
5
Department of Molecular and Medical Genetics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
6
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
7
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: ecker@salk.edu.
8
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: mitalipo@ohsu.edu.

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.

KEYWORDS:

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

PMID:
27840020
PMCID:
PMC5218919
DOI:
10.1016/j.stem.2016.10.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center