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Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants.
Tang, M; Guggilla, R R; Gansemans, Y; Van der Jeught, M; Boel, A; Popovic, M; Stamatiadis, P; Ferrer-Buitrago, M; Thys, V; Van Coster, R; Deforce, D; De Sutter, P; Van Nieuwerburgh, F; Heindryckx, B.
Afiliación
  • Tang M; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Guggilla RR; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Gansemans Y; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
  • Van der Jeught M; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Boel A; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Popovic M; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Stamatiadis P; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Ferrer-Buitrago M; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Thys V; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Van Coster R; Department of Pediatric Neurology and Metabolism, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Deforce D; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
  • De Sutter P; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
  • Van Nieuwerburgh F; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
  • Heindryckx B; Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
Mol Hum Reprod ; 25(12): 797-810, 2019 12 01.
Article en En | MEDLINE | ID: mdl-31651030
Prevention of mitochondrial DNA (mtDNA) diseases may currently be possible using germline nuclear transfer (NT). However, scientific evidence to compare efficiency of different NT techniques to overcome mtDNA diseases is lacking. Here, we performed four types of NT, including first or second polar body transfer (PB1/2T), maternal spindle transfer (ST) and pronuclear transfer (PNT), using NZB/OlaHsd and B6D2F1 mouse models. Embryo development was assessed following NT, and mtDNA carry-over levels were measured by next generation sequencing (NGS). Moreover, we explored two novel protocols (PB2T-a and PB2T-b) to optimize PB2T using mouse and human oocytes. Chromosomal profiles of NT-generated blastocysts were evaluated using NGS. In mouse, our findings reveal that only PB2T-b successfully leads to blastocysts. There were comparable blastocyst rates among PB1T, PB2T-b, ST and PNT embryos. Furthermore, PB1T and PB2T-b had lower mtDNA carry-over levels than ST and PNT. After extrapolation of novel PB2T-b to human in vitro matured (IVM) oocytes and in vivo matured oocytes with smooth endoplasmic reticulum aggregate (SERa) oocytes, the reconstituted embryos successfully developed to blastocysts at a comparable rate to ICSI controls. PB2T-b embryos generated from IVM oocytes showed a similar euploidy rate to ICSI controls. Nevertheless, our mouse model with non-mutated mtDNAs is different from a mixture of pathogenic and non-pathogenic mtDNAs in a human scenario. Novel PB2T-b requires further optimization to improve blastocyst rates in human. Although more work is required to elucidate efficiency and safety of NT, our study suggests that PBT may have the potential to prevent mtDNA disease transmission.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN Mitocondrial / Enfermedades Mitocondriales / Técnicas de Transferencia Nuclear / Cuerpos Polares / Terapia de Reemplazo Mitocondrial Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Hum Reprod Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA REPRODUTIVA Año: 2019 Tipo del documento: Article País de afiliación: Bélgica

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN Mitocondrial / Enfermedades Mitocondriales / Técnicas de Transferencia Nuclear / Cuerpos Polares / Terapia de Reemplazo Mitocondrial Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Hum Reprod Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA REPRODUTIVA Año: 2019 Tipo del documento: Article País de afiliación: Bélgica
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