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Functional Human Oocytes Generated by Transfer of Polar Body Genomes.
Ma, Hong; O'Neil, Ryan C; Marti Gutierrez, Nuria; Hariharan, Manoj; Zhang, Zhuzhu Z; He, Yupeng; Cinnioglu, Cengiz; Kayali, Refik; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Koski, Amy; Nery, Joseph; Castanon, Rosa; Tippner-Hedges, Rebecca; Ahmed, Riffat; Van Dyken, Crystal; Li, Ying; Olson, Susan; Battaglia, David; Lee, David M; Wu, Diana H; Amato, Paula; Wolf, Don P; Ecker, Joseph R; Mitalipov, Shoukhrat.
Afiliação
  • Ma H; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • O'Neil RC; 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.
  • Marti Gutierrez N; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Hariharan M; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Zhang ZZ; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • He Y; 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.
  • Cinnioglu C; IviGen Los Angeles, Torrance, CA 90501, USA.
  • Kayali R; IviGen Los Angeles, Torrance, CA 90501, USA.
  • Kang E; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Lee Y; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Hayama T; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Koski A; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Nery J; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Castanon R; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Tippner-Hedges R; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Ahmed R; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Van Dyken C; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Li Y; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Olson S; Department of Molecular and Medical Genetics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
  • Battaglia D; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Lee DM; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Wu DH; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Amato P; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Wolf DP; Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
  • Ecker JR; 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.
  • Mitalipov S; 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.
Cell Stem Cell ; 20(1): 112-119, 2017 01 05.
Article em En | MEDLINE | ID: mdl-27840020
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oócitos / Genoma Humano / Técnicas de Transferência Nuclear / Corpos Polares Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oócitos / Genoma Humano / Técnicas de Transferência Nuclear / Corpos Polares Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article