Ooplasmic and nuclear transfer to prevent mitochondrial DNA disorders: conceptual and normative issues.
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.


METHODS
After interviews with experts in the field, the relevant literature was searched and analyzed. Bioethical issues were divided into conceptual and normative points.


RESULTS
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.


CONCLUSIONS
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.
Bredenoord
A L
AL
Maastricht University, Health, Ethics and Society and Research Institute GROW, Maastricht, The Netherlands. a.bredenoord@hes.unimaas.nl
Pennings
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de Wert
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D019976:Cloning, Organism / Q000941:ethics; D003593:Cytoplasm / Q000637:transplantation*; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000502:physiology; D033041:Embryo Research / Q000941:ethics; D006801:Humans; D028361:Mitochondrial Diseases / Q000517:prevention & control*; D053652:Nuclear Transfer Techniques / Q000941:ethics*; D018587:Oocyte Donation / Q000941:ethics; D009865:Oocytes / Q000637:transplantation / Q000648:ultrastructure*
D004272:DNA, Mitochondrial