title: Assessment of nuclear transfer techniques to prevent the transmission of heritable mitochondrial disorders without compromising embryonic development competence in mice.
abstract: To evaluate and compare mitochondrial DNA (mtDNA) carry-over and embryonic development potential between different nuclear transfer techniques we performed germinal vesicle nuclear transfer (GV NT), metaphase-II spindle-chromosome-complex (MII-SCC) transfer and pronuclear transfer (PNT) in mice. No detectable mtDNA carry-over was seen in most of the reconstructed oocytes and embryos. No significant differences were seen in mtDNA carry-over rate between GV NT (n=20), MII-SCC transfer (0.29 ± 0.63; n=21) and PNT (0.29 ± 0.75; n=25). Blastocyst formation was not compromised after either PNT (88%; n=18) or MII-SCC transfer (86%; n=27). Further analysis of blastomeres from cleaving embryos (n=8) demonstrated undetectable mtDNA carry-over in all but one blastomere. We show that NT in the germ line is potent to prevent transmission of heritable mtDNA disorders with the applicability for patients attempting reproduction.
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: jitesh.neupane@ugent.be.
authors.forename: Jitesh
authors.initials: J
authors.lastname: Neupane
authors.affiliation: Laboratory for Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium. Electronic address: mado.vandewoestyne@gmail.com.
authors.forename: Mado
authors.initials: M
authors.lastname: Vandewoestyne
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: sabitri.ghimire@ugent.be.
authors.forename: Sabitri
authors.initials: S
authors.lastname: Ghimire
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: yuechao.lu@ugent.be.
authors.forename: Yuechao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: chenqian48928@gmail.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium. Electronic address: Rudy.vancoster@ugent.be.
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: Jan.Gerris@uzgent.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerris
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: tom.deroo@ugent.be.
authors.forename: Tom
authors.initials: T
authors.lastname: Deroo
authors.affiliation: Laboratory for Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium. Electronic address: dieter.deforce@ugent.be.
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: petra.desutter@ugent.be.
authors.forename: Petra
authors.initials: P
authors.lastname: De Sutter
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: bjorn.heindryckx@ugent.be.
authors.forename: Björn
authors.initials: B
authors.lastname: Heindryckx
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000502:physiology; D001757:Blastomeres / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000032:analysis; D047108:Embryonic Development; D005260:Female; D008297:Male; D051379:Mice; D028361:Mitochondrial Diseases / Q000517:prevention & control*; D053652:Nuclear Transfer Techniques / Q000009:adverse effects*; D011247:Pregnancy
chemical_list: D004272:DNA, Mitochondrial
keywords: Embryonic development potential; Mitochondrial DNA (mtDNA); Nuclear transfer (NT); mtDNA carry-over