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From contemplation to classification of chromosomal mosaicism in human preimplantation embryos

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Abstract

Chromosomal mosaicism is a hallmark of early human embryo development. The last decade yielded an enormous amount of information about diversity and prevalence of mosaicism in preimplantation embryos due to progress in preimplantation genetic testing of aneuploidies (PGT-A) based exclusively on molecular karyotyping of trophectoderm biopsy. However, the inner cell mass karyotype is still missing for mosaic embryos affecting the success rate of assisted reproductive medicine. Here, a classification model of chromosomal mosaicism is proposed based on the analysis of the primary zygote karyotype, the timing and types of primary and secondary chromosome segregation errors, and the distribution of mosaic cell clones between different embryonic and extraembryonic compartments of the blastocyst. Five basic principles for mosaicism analysis are introduced, namely, the estimation of the primary zygote karyotype, the investigation of additional sample point, the requirement of the second time point analysis, the delineating of reciprocity of chromosome segregation, and comprehensive chromosome screening at the single-cell level. The suggested model allows the prediction of the inner cell mass karyotype of the blastocyst and its developmental potential based on information from trophectoderm biopsy and non-invasive PGT-A using blastocoele fluid sample or spent culture medium as additional sample and time points for analysis and considering the reciprocity as a basic process in chromosome segregation errors between daughter cells in postzygotic cell divisions.

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Funding

The study was supported by the Russian Science Foundation (project № 20-74-00064).

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  1. Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Ushaika Street 10, Tomsk, 634050, Russia

    Igor N. Lebedev & Daria I. Zhigalina

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  1. Igor N. Lebedev
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  2. Daria I. Zhigalina
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Correspondence to Igor N. Lebedev.

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Supplementary Information

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Origin and distribution of chromosomal mosaicism in embryos developed from the monosomic zygote due to mitotic non-disjunction (TIF 971 kb)

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Fig.S2 Origin and distribution of chromosomal mosaicism in embryos developed from the monosomic zygote due to anaphase lagging (TIF 794 kb)

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Fig.S3 Origin and distribution of chromosomal mosaicism in embryos developed from the euploid zygote due to mitotic non-disjunction (TIF 1.49 mb)

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Fig.S4 Origin and distribution of chromosomal mosaicism in embryos developed from the euploid zygote due to anaphase lagging (TIF 1.17 mb)

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Fig.S5 Origin and distribution of chromosomal mosaicism in embryos developed from the trisomic zygote due to mitotic non-disjunction (TIF 1.22 mb)

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Fig.S6 Origin and distribution of chromosomal mosaicism in embryos developed from the trisomic zygote due to anaphase lagging (TIF 1.66 mb)

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Fig.S7 Origin and distribution of chromosomal mosaicism in embryos developed from the tetrasomic zygote due to mitotic non-disjunction (TIF 791 kb)

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Fig.S8 Origin and distribution of chromosomal mosaicism in embryos developed from the tetrasomic zygote due to anaphase lagging (TIF 866 kb)

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Fig.S9 (TIF 793 kb)

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Lebedev, I.N., Zhigalina, D.I. From contemplation to classification of chromosomal mosaicism in human preimplantation embryos. J Assist Reprod Genet 38, 2833–2848 (2021). https://doi.org/10.1007/s10815-021-02304-z

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