Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck

被引:99
作者
Lee, Hyo-Sang [1 ]
Ma, Hong [1 ]
Juanes, Rita Cervera [1 ]
Tachibana, Masahito [1 ]
Sparman, Michelle [1 ]
Woodward, Joy [1 ]
Ramsey, Cathy [1 ]
Xu, Jing [1 ]
Kang, Eun-Ju [1 ]
Amato, Paula [2 ,3 ]
Mair, Georg [4 ]
Steinborn, Ralf [4 ]
Mitalipov, Shoukhrat [1 ,2 ,3 ,5 ,6 ]
机构
[1] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod & Dev Sci, Beaverton, OR 97006 USA
[2] Oregon Hlth & Sci Univ, Dept Obstet, Beaverton, OR 97006 USA
[3] Oregon Hlth & Sci Univ, Dept Gynecol, Beaverton, OR 97006 USA
[4] Univ Vet Med, VetCore Facil Res VetOm, A-1210 Vienna, Austria
[5] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Beaverton, OR 97006 USA
[6] Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, Beaverton, OR 97006 USA
来源
CELL REPORTS | 2012年 / 1卷 / 05期
基金
美国国家卫生研究院;
关键词
CELL NUCLEAR TRANSFER; GENETIC DIAGNOSIS; HUMAN-DISEASE; D-LOOP; MTDNA; HETEROPLASMY; MUTATIONS; OOCYTES; MOUSE; REDUCTION;
D O I
10.1016/j.celrep.2012.03.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The timing and mechanisms of mitochondrial DNA (mtDNA) segregation and transmission in mammals are poorly understood. Genetic bottleneck in female germ cells has been proposed as the main phenomenon responsible for rapid intergenerational segregation of heteroplasmic mtDNA. We demonstrate here that mtDNA segregation occurs during primate preimplantation embryogenesis resulting in partitioning of mtDNA variants between daughter blastomeres. A substantial shift toward homoplasmy occurred in fetuses and embryonic stem cells (ESCs) derived from these heteroplasmic embryos. We also observed a wide range of heteroplasmic mtDNA variants distributed in individual oocytes recovered from these fetuses. Thus, we present here evidence for a previously unknown mtDNA segregation and bottleneck during preimplantation embryo development, suggesting that return to the homoplasmic condition can occur during development of an individual organism from the zygote to birth, without a passage through the germline.
引用
收藏
页码:506 / 515
页数:10
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