La prévention des maladies mitochondriales par mutation de l'ADNmt : de la clinique au transfert de pronoyaux

Mitochondria have the unique characteristic of possessing their own genome, mitochondrial DNA (mtDNA), which is exclusively transmitted by the mother through the cytoplasm of the oocyte. Pathogenic mutations in mtDNA are responsible for mitochondrial diseases. Pronuclear transfer (PNT), not authorized in France, is a technique proposed by the United Kingdom since 2016 to replace the mutated mitochondrial genome of a zygote with a non-mutated one. This method remains widely debated internationally regarding its efficacy and safety. The aim of our work was to evaluate the clinical and and technical feasibility of PNT. Our research confirmed that women carrying a pathogenic variant of mtDNA exhibited ovarian response criteria to stimulationcomparable to a control group. Through a sociological study, we also showed that this technique received support from the majority of women surveyed, primarily because it maintains a genetic link between a woman and her child. Subsequently, we developed the PNT technique using triploid zygotes (3PN) donated for research, following authorization from the Biomedicine Agency. Finally, we assessed the relevance of using 3PN and demonstrated their limitations in terms of development and chromosomal status, even when diploidy was restored. This work opens up perspectives on the feasibility and acceptance of PNT. Future research is necessary to explore the safety of this technique.