Abundance of cell‐free mitochondrial DNA in spent culture medium associated with morphokinetics and blastocyst collapse of expanded blastocysts

Kobayashi, Masaru; Kobayashi, Jun’ichi; Shirasuna, Koumei; Iwata, Hisataka

doi:10.1002/rmb2.12344

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…Embryos that reach the blastocyst stage have, in their culture media, a significantly higher mtDNA/Nuclear DNA ratio compared to embryos that stopped growing or had a slow growth [145]. Similarly, the amount of mtDNA found in the culture media could be correlated to certain morphokinetic parameters of the embryo [146]. Unfortunately, the risk of contamination of the culture media by exogenous DNA or mtDNA from the CCs around the embryo seems to be high, thus limiting the use of this biomarker [147].…”

Section: Free Mtdnamentioning

confidence: 99%

Embryo and Its Mitochondria

et al. 2021

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The mitochondria, present in almost all eukaryotic cells, produce energy but also contribute to many other essential cellular functions. One of the unique characteristics of the mitochondria is that they have their own genome, which is only maternally transmitted via highly specific mechanisms that occur during gametogenesis and embryogenesis. The mature oocyte has the highest mitochondrial DNA copy number of any cell. This high mitochondrial mass is directly correlated to the capacity of the oocyte to support the early stages of embryo development in many species. Indeed, the subtle energetic and metabolic modifications that are necessary for each of the key steps of early embryonic development rely heavily on the oocyte’s mitochondrial load and activity. For example, epigenetic reprogramming depends on the metabolic cofactors produced by the mitochondrial metabolism, and the reactive oxygen species derived from the mitochondrial respiratory chain are essential for the regulation of cell signaling in the embryo. All these elements have also led scientists to consider the mitochondria as a potential biomarker of oocyte competence and embryo viability, as well as a key target for future potential therapies. However, more studies are needed to confirm these findings. This review article summarizes the past two decades of research that have led to the current understanding of mitochondrial functions in reproduction

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Section: Free Mtdnamentioning

confidence: 99%

Embryo and Its Mitochondria

et al. 2021

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“…In recent years, several studies have been performed to evaluate mtDNA as a potential biomarker of embryo vitality. However, there is a lot of controversy as studies performed have reached contradicting conclusions [4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Podolak¹,

Liss

Kiewisz

et al. 2022

CIMB

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A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between mitochondrial DNA (mtDNA) content of cleavage-stage preimplantation embryos and their developmental potential. A total of 69 couples underwent IVF treatment (averaged women age: 36.5, SD 4.9) and produced a total of 314 embryos. A single blastomere was biopsied from each embryo at the cleavage stage (day-3 post-fertilization) subjected to low-pass next generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number amount was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 6.3 ± 7.5 versus 7.1 ± 5.8, p < 0.004; U Mann–Whitney test), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (6.6 ± 4.8 vs. 8.5 ± 13.6, p 0.09), sex (6.6 ± 4.1 vs. 6.2 ± 6.8, p 0.16), maternal age (6.9 ± 7.8 vs. 6.7 ± 4.5, p 0.14) or its ability to implant (7.4 ± 6.6 vs. 5.1 ± 4.6, p 0.18). The mtDNA content cannot serve as a useful biomarker at this point in development. However, further studies investigating both quantitative and qualitative aspects of mtDNA are still required to fully evaluate the relationship between mitochondrial DNA and human reproduction.

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“…There were no differences between IVF and intracytoplasmic sperm injection (ICSI). Further, less (though not significant) cell-free mtDNA was observed in SBM from blastocysts that implanted successfully (Kobayashi et al, 2020a). Interestingly, cell-free mtDNA was found in SBM from porcine embryos too, and the quantity of cell-free mtDNA was affected by embryo ploidy (Kobayashi et al, 2020b).…”

Section: Origin Of Cfdnamentioning

confidence: 93%

Non-invasive preimplantation genetic testing for aneuploidies: an update

Navarro-Sánchez

García-Pascual

Rubio

et al. 2022

Reproductive BioMedicine Online

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Aneuploidy is common among preimplantation human embryos used in assisted reproductive technology. Because abnormal chromosome number can negatively affect reproductive outcome, in vitro-fertilized embryos routinely undergo aneuploidy testing before transfer into the uterus. This testing typically involves an invasive trophectoderm biopsy of a blastocyst-stage embryo. However, emerging evidence indicates that, during in vitro development, embryos secrete cell-free DNA into their culture medium; this phenomenon suggests the potential for an alternative, noninvasive assay for aneuploidy. Embryonic cell-free DNA-based assays exhibit high concordance with trophectoderm biopsies, inner cell mass and the whole blastocyst. Yet, informativity and concordance rates may be influenced by several factors: culture day when medium is collected, contamination with external and/or cumulus cell DNA, and previous manipulation of the embryos. In this review, we discuss non-invasive embryonic cell-free DNA analysis as a biomarker to prioritize blastocysts for transfer to help increase implantation rates and reduce miscarriage rates and time to achieve pregnancy. We also discuss ongoing research on the mechanisms underlying embryonic cell-free DNA secretion and how this impacts its role as a biomarker of aneuploidy.

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Abundance of cell‐free mitochondrial DNA in spent culture medium associated with morphokinetics and blastocyst collapse of expanded blastocysts

Cited by 12 publications

References 37 publications

Embryo and Its Mitochondria

Embryo and Its Mitochondria

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Non-invasive preimplantation genetic testing for aneuploidies: an update

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