Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection?

Houshmand, Massoud; Holme, Elisabeth; Hanson, Charles; Wennerholm, Ulla‐Britt; Hamberger, Lars

doi:10.1007/bf02766114

Cited by 43 publications

(18 citation statements)

References 16 publications

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“…40 We and others have previously been unable to detect significant levels of paternal mtDNA polymorphisms in placenta, even in ICSI where the normal processes governing its elimination might be disrupted. 19,41,42 In the single case report of paternally inherited mtDNA the authors identified mtDNA recombinants using PCR analysis of muscle mtDNA. 43 If this were a common occurrence that involved the germline it should be evident in population studies, and currently there is little or no clear evidence that this is the case.…”

Section: Discussionmentioning

confidence: 99%

Mosaicism for mitochondrial DNA polymorphic variants in placenta has implications for the feasibility of prenatal diagnosis in mtDNA diseases

et al. 2006

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Women who have had a child with mitochondrial DNA (mtDNA) disease need to know the risk of recurrence, but this risk is difficult to estimate because mutant and wild-type (normal) mtDNA coexist in the same person (heteroplasmy). The possibility that a single sample may not reflect the whole organism both impedes prenatal diagnosis of most mtDNA diseases, and suggests radical alternative strategies such as nuclear transfer. We used naturally occurring mtDNA variants to investigate mtDNA segregation in placenta. Using large samples of control placenta, we demonstrated that the level of polymorphic heteroplasmic mtDNA variants is very similar in mother, cord blood and placenta. However, where placental samples were very small (o10 mg) there was clear evidence of variation in the distribution of mtDNA polymorphic variants. We present the first evidence for variation in mutant load, that is, mosaicism for mtDNA polymorphic variants in placenta. This suggests that mtDNA mutants may segregate in placenta and that a single chorionic villous sample (CVS) may be unrepresentative of the whole placenta. Duplicates may be necessary where CVS are small. However, the close correlation of mutant load in maternal, fetal blood and placental mtDNA suggests that the average load in placenta does reflect the load of mutant mtDNA in the baby. Provided that segregation of neutral and pathogenic mtDNA mutants is similar in utero, our results are generally encouraging for developing prenatal diagnosis for mtDNA diseases. Identifying mtDNA segregation in human placenta suggests studies of relevance to placental evolution and to developmental biology.

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Section: Discussionmentioning

confidence: 99%

Mosaicism for mitochondrial DNA polymorphic variants in placenta has implications for the feasibility of prenatal diagnosis in mtDNA diseases

et al. 2006

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“…Such delay could hinder the degradation of the sperm mitochondria and facilitate the persistence of the sperm mtDNA, heteroplasmy, in the embryonic cytoplasm. So far, the completed studies of human ICSI embryos ruled out heteroplasmy (Danan et al, 1999;Houshmand et al, 1997). However, oocytes deficient in their ability to reduce/unmask the sperm mitochondrial capsule could be generated from superficially stimulated cycles and subsequently fail to expose the ubiquitin tag in the sperm mitochondrial membranes.…”

Section: Clinical Considerations: Infertility Diagnostics Vasectomymentioning

confidence: 99%

Ubiquitin‐dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: Killing three birds with one stone

Šutovský

2003

Microscopy Res & Technique

252

181

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Ubiquitin and ubiquitin-like proteins control the degradation of substrates as diverse as cyclins, viral envelope proteins, plasma membrane receptors, and mRNAs. The ubiquitinated substrates are targeted towards the lysosomal or proteasomal degradation sites. The number and position of ubiquitin molecules bound to substrates' lysine residues and the number and position of ubiquitin molecules in polyubiquitin chains determine the astonishing substrate specificity of ubiquitin-mediated proteolysis. Ubiquitin is likely to be expressed in mammalian gametes and embryos at any given developmental step, but the information on ubiquitin dependence of gametogenesis and fertilization is sketchy. Ubiquitin ligases E1, E2, E3, and UBC4 are active in the testis. Ubiquitin and proteasomal subunits can be detected in the human sperm centrosome that undergoes dramatic reduction during spermatid elongation. Spermatid histones are ubiquitinated as they are being transiently replaced by transitional proteins and permanently by protamines. Ubiquitin tagging of the sperm mitochondrial membranes may serve as a death sentence for paternal mitochondria at fertilization, thus promoting the maternal inheritance of mitochondrial DNA (mtDNA) in mammals. The defective spermatozoa become surface-ubiquitinated during sperm descent down the epididymis. Finally, new evidence suggests the involvement of ubiquitin-proteasome pathway in the zona penetration by the acrosome-reacted spermatozoon. Such differential patterns of ubiquitination in the testis and epididymis, and inside the egg, may be necessary for reproductive success in humans and animals. Deciphering and eventually manipulating the ubiquitin-dependent proteolysis in the reproductive system could allow us to redirect the mode of mtDNA inheritance after cloning and ooplasmic transplantation, provide germ line therapy in some cases of male infertility, develop new contraceptives, manage polyspermia during in vitro fertilization, and establish objective markers for infertility diagnostics, semen evaluation, and prediction of future fertility.

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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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Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection?

Abstract: During intracytoplasmic sperm injection (ICSI

Cited by 43 publications

References 16 publications

Mosaicism for mitochondrial DNA polymorphic variants in placenta has implications for the feasibility of prenatal diagnosis in mtDNA diseases

Mosaicism for mitochondrial DNA polymorphic variants in placenta has implications for the feasibility of prenatal diagnosis in mtDNA diseases

Ubiquitin‐dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: Killing three birds with one stone

Does Human mtDNA Recombine?

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