Bredenoord A L, Pennings G, de Wert G
Maastricht University, Health, Ethics and Society and Research Institute GROW, Maastricht, The Netherlands.
Hum Reprod Update. 2008 Nov-Dec;14(6):669-78. doi: 10.1093/humupd/dmn035. Epub 2008 Sep 4.
BACKGROUND; Mitochondrial DNA (mtDNA) disorders are an important cause of human diseases. In view of the limitations of prenatal diagnosis and preimplantation genetic diagnoses, alternatives such as ooplasmic transfer (OT) and nuclear transfer (NT) have been proposed to prevent the transmission of mtDNA mutations. Both OT and NT are radical in the sense that they do not entail genetic selection, but genetic intervention to correct the genetic cause of the disease.
After interviews with experts in the field, the relevant literature was searched and analyzed. Bioethical issues were divided into conceptual and normative points.
OT is the transfer of normal mitochondria to a carrier's oocyte containing mutant mtDNA. In case of NT, a donated oocyte is enucleated and replaced with the nuclear DNA from a woman carrying a mtDNA mutation. NT can be performed both before and after in vitro fertilization, respectively, with the nucleus of an unfertilized oocyte, with the pronuclei of the zygote, or with the nucleus of a blastomere of an embryo. Conceptual questions regard whether these techniques amount to germ-line modification and human cloning. Normative questions concern, among others, the significance of intervening in the mtDNA, the implications of having 'three genetic parents', the ethics of oocyte donation and the health and safety risks for children conceived as a result of one of these techniques.
Further interdisciplinary debate and research is needed to determine whether a clinical application of OT and NT can be morally justified, and if so, under which conditions.
背景；线粒体DNA（mtDNA）疾病是人类疾病的一个重要病因。鉴于产前诊断和植入前基因诊断的局限性，已提出诸如卵质转移（OT）和核转移（NT）等替代方法来防止mtDNA突变的传递。OT和NT从某种意义上来说都是激进的，因为它们不是进行基因选择，而是进行基因干预以纠正疾病的遗传病因。
在采访该领域专家后，检索并分析了相关文献。生物伦理问题分为概念性和规范性要点。
OT是将正常线粒体转移到含有突变mtDNA的携带者卵母细胞中。在NT的情况下，将捐赠的卵母细胞去核，并用携带mtDNA突变的女性的核DNA进行替换。NT可分别在体外受精之前和之后进行，分别用未受精卵母细胞的细胞核、受精卵的原核或胚胎卵裂球的细胞核进行操作。概念性问题涉及这些技术是否等同于生殖系修饰和人类克隆。规范性问题尤其包括干预mtDNA的意义、拥有“三个遗传父母”的影响、卵母细胞捐赠的伦理以及因这些技术之一受孕的儿童的健康和安全风险。
需要进一步开展跨学科辩论和研究，以确定OT和NT的临床应用在道德上是否合理，如果合理，在何种条件下合理。
