Intracytoplasmic injection of spermatozoa does not appear to alter the mode of mitochondrial DNA inheritance

Torroni, Antonio; D'Urbano, Leila; Rengo, Chiara; Scozzari, Rosaria; Sbracia, Marco; Manna, Claudio; Cavazzini, C; Sellitto, Daniele

doi:10.1093/humrep/13.6.1747

Cited by 18 publications

(10 citation statements)

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“…By each of the above assisted reproductive technologies (ART), foreign mitochondria are introduced into the oocyte cytoplasm, where they may reproduce autonomously unless they are recognized and properly processed by the egg's cytoplasmic machinery. Although the first reports on mtDNA inheritance after ICSI suggest that such human embryos can properly recognize and process the mtDNA of the injected sperm [61,62], other studies [63] show that even normal, let alone multipronuclear embryos generated by ART, may promote the persistence of paternal mtDNA in their cytoplasm. It is possible that the intact plasma membrane on the surface of the microinjected sperm can delay the processing of the sperm axoneme in a manner similar to the aberrant remodeling of the sperm nucleus after ICSI [31,32].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitinated Sperm Mitochondria, Selective Proteolysis, and the Regulation of Mitochondrial Inheritance in Mammalian Embryos1

Šutovský

Moreno

Ramalho‐Santos

et al. 2000

Biology of Reproduction

375

251

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The strictly maternal inheritance of mitochondria and mitochondrial DNA (mtDNA) in mammals is a developmental paradox promoted by an unknown mechanism responsible for the destruction of the sperm mitochondria shortly after fertilization. We have recently reported that the sperm mitochondria are ubiquitinated inside the oocyte cytoplasm and later subjected to proteolysis during preimplantation development (P. Sutovsky et al., Nature 1999; 402:371-372). Here, we provide further evidence for this process by showing that the proteolytic destruction of bull sperm mitochondria inside cow egg cytoplasm depends upon the activity of the universal proteolytic marker, ubiquitin, and the lysosomal apparatus of the egg. Binding of ubiquitin to sperm mitochondria was visualized by monospecific antibodies throughout pronuclear development and during the first embryonic divisions. The recognition and disposal of the ubiquitinated sperm mitochondria was prevented by the microinjection of anti-ubiquitin antibodies and by the treatment of the fertilized zygotes with lysosomotropic agent ammonium chloride. The postfecundal ubiquitination of sperm mitochondria and their destruction was not seen in the hybrid embryos created using cow eggs and sperm of wild cattle, gaur, thus supporting the hypothesis that sperm mitochondrion destruction is species specific. The initial ligation of ubiquitin molecules to sperm mitochondrial membrane proteins, one of which could be prohibitin, occurs during spermatogenesis. Even though the ubiquitin cross-reactivity was transiently lost from the sperm mitochondria during epididymal passage, likely as a result of disulfide bond cross-linking, it was restored and amplified after fertilization. Ubiquitination therefore may represent a mechanism for the elimination of paternal mitochondria during fertilization. Our data have important implications for anthropology, treatment of mitochondrial disorders, and for the new methods of assisted procreation, such as cloning, oocyte cytoplasm donation, and intracytoplasmic sperm injection.

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Section: Discussionmentioning

confidence: 99%

Ubiquitinated Sperm Mitochondria, Selective Proteolysis, and the Regulation of Mitochondrial Inheritance in Mammalian Embryos1

Šutovský

Moreno

Ramalho‐Santos

et al. 2000

Biology of Reproduction

375

251

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“…Paternal inheritance has never been observed in humans, either in pedigree studies (Jazin et al 1998;Parsons et al 1997;Sigurdardottir et al 2000;Soodyall et al 1997), or in cases of artificial fertilization using intracytoplasmic sperm injection (ICSI) (Danan et al 1994;Houshmand et al 1997;Torroni et al 1998). However, the numbers of cases that have been examined is small; only 38 ICSI cases have been investigated, and the total number of generational events considered in pedigrees probably does not exceed 2500, even if all the pedigrees used to establish maternal inheritance of various genetic diseases are taken into account.…”

Section: Paternal Leakagementioning

confidence: 99%

Does Human mtDNA Recombine?

Eyre‐Walker

Awadalla

2001

Journal of Molecular Evolution

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Abstract. In this article we review the evidence for and against recombination in human mtDNA. If recombination occurs, there needs to be a route by which genetic material can incorporate itself into the mitochondrial genome, and hence between mitochondrial lineages. We review the evidence for possible routes and then review the current state of the population genetic evidence for recombination. We conclude that there is no firmly established route by which recombination can occur, and that while some of the population genetic evidence is suggestive of recombination, it is far from conclusive.

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“…The number of mitochondrial DNAs (mtDNAs) in each cell varies from 50 to 800 copies in sperm cells and to 80,000-600,000 copies in oocytes [4][5][6]. Mitochondria are continuously turned over along with mtDNA with a half-life of 3-4 weeks in postmitoic cells [7].…”

Section: Mitochondrial Deletionsmentioning

confidence: 99%