Failure of elimination of paternal mitochondrial DNA in abnormal embryos

doi:10.1016/S0140-6736(99)03842-8

The Lancet

Volume 355, Issue 9199, 15 January 2000, Page 200

https://doi.org/10.1016/S0140-6736(99)03842-8 Get rights and content

Summary

Paternal mitochondrial DNA is normally eliminated from mammalian embryos. We have shown the presence of paternal mtDNA at the blastocyst stage in some abnormal human embryos.

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There are more references available in the full text version of this article.

Cited by (81)

Mitochondria in Ovarian Aging and Reproductive Longevity
2020, Ageing Research Reviews
Mitochondrial dysfunction is one of the hallmarks of aging. Consistently mitochondrial DNA (mtDNA) copy number and function decline with age in various tissues. There is increasing evidence to support that mitochondrial dysfunction drives ovarian aging. A decreased mtDNA copy number is also reported during ovarian aging. However, the mitochondrial mechanisms contributing to ovarian aging and infertility are not fully understood. Additionally, investigations into mitochondrial therapies to rejuvenate oocyte quality, select viable embryos and improve mitochondrial function may help enhance fertility or extend reproductive longevity in the future. These therapies include the use of mitochondrial replacement techniques, quantification of mtDNA copy number, and various pharmacologic and lifestyle measures. This review aims to describe the key evidence and current knowledge of the role of mitochondria in ovarian aging and identify the emerging potential options for therapy to extend reproductive longevity and improve fertility.
Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance
2020, Forensic Science International: Genetics
Citation Excerpt :
As early as 1999, Brenner et al. [24] described the presence of heteroplasmy after human ooplasmic transplantation (a technique developed in the late 90′s). In 2000, St John et al. [25] described the detection of paternal mtDNA after IVF and intracytoplasmic sperm injection (ICSI) treatment. In 2001, Barritt et al. [26] stated that ooplasmic transfer from fertile donor oocytes into patient oocytes led to the birth of about 30 children.
A breakthrough article published in PNAS by Luo et al. challenges a central dogma in biology which states that the mitochondrial DNA (mtDNA) in humans is inherited exclusively from the mother. We re-analyzed original FASTQ files and results reported by Luo et al. to investigate methodological issues (e.g. nuclear mitochondrial DNA or NUMTs, DNA rearrangements) that could lead to biological misinterpretations. A comprehensive analysis of their data reveals several methodological and analytical issues that must be carefully addressed before challenging the current paradigm. We first show that the probability of the findings described by the authors is extremely small (most likely below 10⁻³⁷). The sequencing replicates from the same donors show aberrations in the variants detected that need further investigation to exclude contributions from other sources or methodological artifacts. Applying the principle of reductio ad absurdum, we demonstrate that the nuclear factor invoked by the authors to explain the phenomenon would need to be extraordinarily complex and precise to preclude linear accumulation of mtDNA lineages across generations, which would make the appearance of mixed haplotypes a much more frequent event in the population. We discuss alternate scenarios that explain findings of the same nature as reported by Luo et al., in the context of in-vitro fertilization and therapeutic mtDNA replacement ooplasmic transplantation.
Heredity and segregation of mtDNA
2020, The Human Mitochondrial Genome: From Basic Biology to Disease
It is generally accepted that human mtDNA is transmitted uniparentally, exclusively down the maternal line, in contrast to the biparental pattern of inheritance seen in the nucleus. This unusual mode of transmission means that normal Mendelian laws of inheritance cannot be applied when discussing mtDNA. To explore the heredity and segregation of mtDNA further, in this chapter we will consider the following questions:
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  How is strict maternal inheritance of mtDNA maintained in humans?
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  Is there evidence for paternal mtDNA inheritance in humans?
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  How do mtDNA mutations segregate during germline transmission?
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  How do mtDNA mutations segregate in somatic tissues?
Delayed elimination of paternal mtDNA in the interspecific hybrid of Pelteobagrus fulvidraco and Pelteobagrus vachelli during early embryogenesis
2019, Gene
Citation Excerpt :
However, the offsprings of hybrid yellow catfish have a high rate of abnormal and defective embryos than the offsprings of P. fulvidraco, which directly increases the cost of artificial reproduction. Previous studies have indicated that the occurrence of abnormal or diseased phenotypes during embryogenesis was relevant to the failure of elimination of paternal mtDNA (St John et al., 2000; Hua et al., 2012). In our study, we attempted to investigate whether paternal mitochondria were not efficiently eliminated in hybrid yellow catfish when compared to P. fulvidraco, which may be a factor for a high malformation rate in hybrid yellow catfish.
Mitochondrial homoplasmy is essential for normal development, as its heteroplasmy usually leads to abnormal or diseased phenotypes in mammals. So far, diverse mechanisms have been proposed to play roles in ensuring uniparental inheritance of mitochondria in many organisms. In recent years, hybrid yellow catfish from mating female yellow catfish (Pelteobagrus fulvidraco) with male darkbarbel catfish (Pelteobagrus vachelli) has been widely cultured in China due to its fast-growing. However, a high rate of abnormal and defective embryos was observed in the offsprings of hybrid yellow catfish. In this study, we systematically investigated the elimination process of paternal mitochondrial DNA (mtDNA) in yellow catfish and hybrid yellow catfish. The mtDNA contents significantly decreased in the isolated mature sperm compared with the semen. Different from the elimination of paternal mtDNA after fertilization in yellow catfish, paternal mtDNA was retained in the developmental embryos of hybrid yellow catfish as later as gastrula stage, indicating a delay of elimination for paternal mtDNA and mitochondrial heteroplasmy during embryogenesis in hybrid yellow catfish. Altogether, the present study suggests that mitochondrial heteroplasmy may affect embryonic development of hybrid progeny between catfish species.
The control of mtDNA replication during differentiation and development
2014, Biochimica et Biophysica Acta - General Subjects
Mitochondrial DNA (mtDNA) is important for energy production as it encodes some of the key genes of electron transfer chain, where the majority of cellular energy is generated through oxidative phosphorylation (OXPHOS). MtDNA replication is mediated by nuclear DNA-encoded proteins or enzymes, which translocate to the mitochondria, and is strictly regulated throughout development. It starts with approximately 200 copies in each primordial germ cell and these copies undergo expansion and restriction events at various stages of development.
I describe the patterns of mtDNA replication at key stages of development. I explain that it is essential to regulate mtDNA copy number and to establish the mtDNA set point in order that the mature, specialised cell acquires the appropriate numbers of mtDNA copy to generate sufficient adenosine triphosphate (ATP) through OXPHOS to undertake its specialised function. I discuss how these processes are dependent on the controlled expression of the nuclear-encoded mtDNA-specific replication factors and that this can be modulated by mtDNA haplotypes. I discuss how these events are altered by certain assisted reproductive technologies, some of which have been proposed to prevent the transmission of mutant mtDNA and others to overcome infertility. Furthermore, some of these technologies are predisposed to transmitting two or more populations of mtDNA, which can be extremely harmful.
The failure to regulate mtDNA replication and mtDNA transmission during development is disadvantageous.
Manipulation of oocytes and embryos can lead to significant implications for the maternal-only transmission of mtDNA.
This article is part of a Special Issue entitled Frontiers of mitochondrial research.
Sperm mitochondria in reproduction: Good or bad and where do they go?
2013, Journal of Genetics and Genomics
Citation Excerpt :
In most mammals, along with the sperm genome, the sperm tail and midpiece are also incorporated into the oocyte during fertilization (Ankel-Simons and Cummins, 1996); however, it was also reported that due to the giant volume of the sperm midpiece and tail in Chinese hamster (Cricetulus griseus), its mitochondria remained outside the zygote after fertilization (Pickworth and Change, 1969; Yanagimachi et al., 1983). Although in some cases such as in mouse interspecies crossing (Gyllensten et al., 1991; Kaneda et al., 1995), and human abnormal embryos, paternal mtDNA was detected (St John et al., 2000), maternal mitochondrial inheritance is accepted as the most prevalent phenomenon in mammals. By utilizing immunofluorescence methods, sperm mitochondria ubiquitination during spermatogenesis was found in rhesus monkeys and cows, which suggested that the ubiquitin–proteasome-dependent proteolytic machinery might be involved in the degradation of sperm mitochondria after fertilization (Sutovsky et al., 1999).
The mitochondrion is the major energy provider to power sperm motility. In mammals, aside from the nuclear genome, mitochondrial DNA (mtDNA) also contributes to oxidative phosphorylation to impact production of ATP by coding 13 polypeptides. However, the role of sperm mitochondria in fertilization and its final fate after fertilization are still controversial. The viewpoints that sperm bearing more mtDNA will have a better fertilizing capability and that sperm mtDNA is actively eliminated during early embryogenesis are widely accepted. However, this may be not true for several mammalian species, including mice and humans. Here, we review the sperm mitochondria and their mtDNA in sperm functions, and the mechanisms of maternal mitochondrial inheritance in mammals.

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Research LettersFailure of elimination of paternal mitochondrial DNA in abnormal embryos

Summary

Maternal inheritance of mouse mtDNA in interspecific hybrids: segregation of the leaked paternal mtDNA followed by the prevention of subsequent paternal leakage

Genetics

Mitochondrial mutations and male infertility

Nat Med

Research Letters
Failure of elimination of paternal mitochondrial DNA in abnormal embryos