@article{1943d61687534fc4a6d8e6f8e1b3c1d6,
title = "Functional Human Oocytes Generated by Transfer of Polar Body Genomes",
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",
author = "Hong Ma and O'Neil, {Ryan C.} and {Marti Gutierrez}, Nuria and Manoj Hariharan and Zhang, {Zhuzhu Z.} and Yupeng He and Cengiz Cinnioglu and Refik Kayali and Eunju Kang and Yeonmi Lee and Tomonari Hayama and Amy Koski and Joseph Nery and Rosa Castanon and Rebecca Tippner-Hedges and Riffat Ahmed and {Van Dyken}, Crystal and Ying Li and Susan Olson and David Battaglia and Lee, {David M.} and Wu, {Diana H.} and Paula Amato and Wolf, {Don P.} and Ecker, {Joseph R.} and Shoukhrat Mitalipov",
note = "Funding Information: The authors acknowledge the OHSU Embryonic Stem Cell Research Oversight Committee and the Institutional Review Board for providing oversight and guidance. We thank all study participants for tissue donations and the Women's Health Research Unit staff at the Center for Women's Health, University Fertility Consultants, and Reproductive Endocrinology and Infertility Division in the Department of Obstetrics and Gynecology of Oregon Health and Science University for their support and procurement of human gametes. We are grateful to Dr. Cecilia Penedo for microsatellite analysis and to Dr. Stefanie Kaech and Aurelie Snyder in the Advanced Light Microscopy Core at OHSU for imaging studies. This investigation was supported by grants from the Leducq Foundation and OHSU institutional funds. Z.Z.Z. was supported by the Dan and Martina Lewis Biophotonics Fellows Program. Transcriptome, methylome, and physical mapping studies were supported by the Salk International Council Chair fund endowment and the Mary K. Chapman Foundation to J.R.E. J.R.E. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jan,
day = "5",
doi = "10.1016/j.stem.2016.10.001",
language = "English (US)",
volume = "20",
pages = "112--119",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",
}