Escuela de Medicina Veterinaria, Universidad San Francisco de Quito USFQ, Quito, Ecuador; Instituto de Investigaciones en Biomedicina iBioMed, Universidad San Francisco de Quito USFQ, Quito, Ecuador; University of Montpellier, France, Institute of Regenerative Medicine and Biotherapies, IRMB, Center Hospitalier Universitaire, Montpellier, France; Mito-Act Research Consortium, Quito, Ecuador.
Instituto de Investigaciones en Biomedicina iBioMed, Universidad San Francisco de Quito USFQ, Quito, Ecuador; Mito-Act Research Consortium, Quito, Ecuador; Biología, Colegio de Ciencias Biológicas y Ambientales COCIBA, Universidad San Francisco de Quito USFQ, Quito, Ecuador.
Mitochondrion. 2022 Jul;65:102-112. doi: 10.1016/j.mito.2022.05.006. Epub 2022 May 23.
Oocytes may carry mutations in their mitochondrial DNA (mtDNA) which affect fertility and embryo development leading to hereditary diseases or rejection. Mitochondrial replacement therapies (MRTs) such as polar body transfer, spindle transfer and pronuclear transfer, aim to change dysfunctional to normal mitochondria inside oocytes and zygotes resulting in healthier offspring. Even with promising results, MRTs techniques are invasive to oocytes and may negatively affect their viability and the success of the procedure. This article shows early evidence of the use of MitoCeption, a mitochondria transfer/transplant (AMT/T) technique to possibly induce the internalization of exogenous mitochondria in a dose-dependent manner to recipient oocytes in comparison to coincubation. By using human isolated mitochondria in a mix obtained from different donors we were able to identify their mtDNA in murine oocytes by qPCR. Fluorescence microscopy showed that exogenous and transferred mitochondria (MitoTracker ® Red) by MitoCeption were internalized in oocytes and zygotes (CellTracker® Green). After maintaining mitocepted zygotes to two-cell embryos, we transferred them to subrogate female mice and obtained healthy mice pups; however, without clear evidence of the maintenance of human mtDNA in the tissues of mice pups. These early results are puzzling, and they open the path to generate more research regarding the use of MitoCeption in comparison to coincubation in order to transfer mitochondria to oocytes using less invasive procedures.
卵母细胞可能携带线粒体 DNA（mtDNA）突变，这些突变会影响生育能力和胚胎发育，导致遗传疾病或排斥。线粒体替代疗法（MRTs），如极体转移、纺锤体转移和原核转移，旨在改变卵母细胞和受精卵内功能失调的线粒体为正常线粒体，从而产生更健康的后代。尽管 MRTs 技术取得了有希望的结果，但这些技术对卵母细胞具有侵入性，可能会对其活力和手术成功率产生负面影响。本文展示了使用 MitoCeption 的早期证据，MitoCeption 是一种线粒体转移/移植（AMT/T）技术，可能以剂量依赖的方式诱导外源性线粒体内化到受体卵母细胞中，与共孵育相比。通过使用来自不同供体的混合物中分离的人线粒体，我们能够通过 qPCR 鉴定在鼠卵母细胞中的 mtDNA。荧光显微镜显示，通过 MitoCeption 内化的外源性和转移的线粒体（MitoTracker®Red）进入卵母细胞和受精卵（CellTracker®Green）。在将 mitocepted 受精卵维持到 2 细胞胚胎后，我们将其转移到替代雌性小鼠中，并获得了健康的小鼠幼崽；然而，没有明确的证据表明人类 mtDNA 在小鼠幼崽的组织中得到了维持。这些早期结果令人费解，它们为使用 MitoCeption 与共孵育进行比较，以使用侵入性更小的程序将线粒体转移到卵母细胞中，开辟了更多研究的道路。
