Li Ruiqi, Wen Bingqiang, Zhao Haijing, Ouyang Nengyong, Ou Songbang, Wang Wenjun, Han Jianyong, Yang Dongzi
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, People's Republic of China.
J Assist Reprod Genet. 2017 Aug;34(8):1027-1033. doi: 10.1007/s10815-017-0948-9. Epub 2017 Jun 1.
The purpose of this study was to evaluate the effects of mitochondrial supplementation (MS) on early embryonic development and to assess the safety of MS treatments using induced pluripotent stem cells (iPSCs) as the mitochondrial donor.
In this study, we evaluated the effect of MS on early embryonic development using induced pluripotent stem cells (iPSCs) as the donor. Mouse zygotes were injected with either mitochondria from iPSCs or a vehicle solution. Several parameters were evaluated, including the rates of blastocyst formation and implantation, the weight of E13.5 embryos and placentas, the distribution of the donor mitochondrial DNA (mtDNA), and the pattern of methylation in the differentially methylated regions (DMRs) of the H19 and Snrpn genes.
We found that neither the rates of blastocyst formation and implantation nor the weights of E13.5 embryos and placentas were significantly different between the MS and control groups. Additionally, the mtDNA from the iPSC donors could be detected in the muscle tissue of four fetuses and all placentas in the MS group. Finally, the methylation patterns of H19 and Snrpn DMRs remained unchanged by MS.
iPSC-derived mtDNA was directly involved in the process of embryonic development after MS. No adverse effects were seen when using iPSCs as a mitochondrial donor, but it remains to be seen whether this method can improve embryonic development, especially in older mice.
本研究旨在评估线粒体补充（MS）对早期胚胎发育的影响，并评估以诱导多能干细胞（iPSC）作为线粒体供体进行MS治疗的安全性。
在本研究中，我们以诱导多能干细胞（iPSC）作为供体，评估了MS对早期胚胎发育的影响。将来自iPSC的线粒体或赋形剂溶液注射到小鼠受精卵中。评估了几个参数，包括囊胚形成率和着床率、E13.5胚胎和胎盘的重量、供体线粒体DNA（mtDNA）的分布以及H19和Snrpn基因差异甲基化区域（DMR）的甲基化模式。
我们发现，MS组和对照组之间的囊胚形成率和着床率以及E13.5胚胎和胎盘的重量均无显著差异。此外，在MS组的四个胎儿的肌肉组织和所有胎盘中都能检测到来自iPSC供体的mtDNA。最后，MS并未改变H19和Snrpn DMR的甲基化模式。
MS后，iPSC来源的mtDNA直接参与胚胎发育过程。以iPSC作为线粒体供体未见不良反应，但该方法能否改善胚胎发育，尤其是在老年小鼠中，仍有待观察。
