Chappel Scott
OvaScience, Inc., 215 First Street, Suite 240, Cambridge, MA 02142, USA.
Obstet Gynecol Int. 2013;2013:183024. doi: 10.1155/2013/183024. Epub 2013 May 16.
The oocyte requires a vast supply of energy after fertilization to support critical events such as spindle formation, chromatid separation, and cell division. Until blastocyst implantation, the developing zygote is dependent on the existing pool of mitochondria. That pool size within each cell decreases with each cell division. Mitochondria obtained from oocytes of women of advanced reproductive age harbor DNA deletions and nucleotide variations that impair function. The combination of lower number and increased frequency of mutations and deletions may result in inadequate mitochondrial activity necessary for continued embryo development and cause pregnancy failure. Previous reports suggested that mitochondrial activity within oocytes may be supplemented by donor cytoplasmic transfer at the time of intracytoplasmic sperm injection (ICSI). Those reports showed success; however, safety concerns arose due to the potential of two distinct populations of mitochondrial genomes in the offspring. Mitochondrial augmentation of oocytes is now reconsidered in light of our current understanding of mitochondrial function and the publication of a number of animal studies. With a better understanding of the role of this organelle in oocytes immediately after fertilization, blastocyst and offspring, mitochondrial augmentation may be reconsidered as a method to improve oocyte quality.
受精后,卵母细胞需要大量能量供应,以支持诸如纺锤体形成、染色单体分离和细胞分裂等关键事件。在囊胚着床之前,发育中的受精卵依赖于现有的线粒体库。每个细胞内的线粒体库大小会随着每次细胞分裂而减少。从高龄育龄女性的卵母细胞中获取的线粒体存在DNA缺失和核苷酸变异,这些会损害线粒体功能。线粒体数量减少以及突变和缺失频率增加,可能会导致胚胎持续发育所需的线粒体活性不足,进而导致妊娠失败。先前的报告表明,在卵胞浆内单精子注射(ICSI)时,通过供体细胞质转移可能会补充卵母细胞内的线粒体活性。这些报告显示取得了成功;然而,由于后代中可能存在两种不同的线粒体基因组,引发了安全担忧。鉴于我们目前对线粒体功能的理解以及一些动物研究的发表,现在重新考虑对卵母细胞进行线粒体增强。随着对这种细胞器在受精后即刻、囊胚和后代的卵母细胞中的作用有了更深入的了解,线粒体增强可能会被重新视为一种改善卵母细胞质量的方法。