Depletion of aneuploid cells in human embryos and gastruloids

Yang, Min; Rito, Tiago; Metzger, Jakob; Naftaly, Jeffrey A.; Soman, Rohan; Hu, Jianjun; Albertini, David F.; Barad, David H.; Brivanlou, Ali H; Gleicher, Norbert

doi:10.1038/s41556-021-00660-7

Cited by 104 publications

(84 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed a tendency toward an increased number of chromosomal abnormalities in the BF depending on the degree of maturity of the blastocyst from stage 3 to 5 of blastulation [88], according to the criteria set by Gardner et al [89], which involve the assessment of blastocoel expansion and hatching status, the presence of a cohesive layer, and some other parameters. These results indicate a more intensive elimination of cells with chromosomal aneuploidies during the transition from stage 3 to stage 5 of blastocyst development, supporting the hypothesis of self-correction of the embryo karyotype [74].…”

Section: Reciprocal Aneuploidy As An Indicator Of De Novo Postzygotic Mitotic Errors In Chromosome Segregationsupporting

confidence: 78%

“…The literature presents studies that confirm that cell death occurs predominantly in the ICM [70][71][72] and that there are only low levels of apoptosis in TE cells in mouse embryos [70,72,73]. Moreover, early development and cell specification modelled in micropatterned human "gastruloids" also show that aneuploid cells are depleted from embryonic germ layers, but not from extraembryonic tissue [74].…”

Section: Reciprocal Aneuploidy As An Indicator Of De Novo Postzygotic Mitotic Errors In Chromosome Segregationmentioning

confidence: 99%

See 1 more Smart Citation

From contemplation to classification of chromosomal mosaicism in human preimplantation embryos

Lebedev

Жигалина

2021

J Assist Reprod Genet

View full text Add to dashboard Cite

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.

show abstract

Section: Reciprocal Aneuploidy As An Indicator Of De Novo Postzygotic Mitotic Errors In Chromosome Segregationsupporting

confidence: 78%

Section: Reciprocal Aneuploidy As An Indicator Of De Novo Postzygotic Mitotic Errors In Chromosome Segregationmentioning

confidence: 99%

From contemplation to classification of chromosomal mosaicism in human preimplantation embryos

Lebedev

Жигалина

2021

J Assist Reprod Genet

View full text Add to dashboard Cite

show abstract

“…Furthermore, as continuous efforts are being produced to develop smart and dynamic microenvironments which can evolve in response to cell behaviours ( Badeau and DeForest, 2019 ; Rapp and DeForest, 2020 ; Uto et al, 2020 ), we can anticipate that new avenues will emerge to better mimic organogenesis and later development in a standardised manner. Finally, highly standardised in vitro models will continue to help us reveal unnoticed, yet important, developmental phenotypes ( Galgoczi et al, 2021 preprint; Haremaki et al, 2019 ; Krieger et al, 2019 ; Yang et al, 2021 ) to better understand diseases with a developmental origin, as well as gene-environment interactions during development.…”

Section: Discussionmentioning

confidence: 99%

“…Micropatterned colonies also offer robust assays for development of regenerative therapies, for example to identify the cell lines that are best suited to generate specific clinically-relevant cell types ( Nazareth et al, 2013 ; Tewary et al, 2019 ). The strengths of micropattern systems also make them excellent platforms for investigating the early developmental origins of certain degenerative diseases ( Galgoczi et al, 2021 preprint; Haremaki et al, 2019 ; Krieger et al, 2019 ) or to understand chromosomal instability and mosaicism during early development ( Yang et al, 2021 ).…”

Section: Micropattern Models Of Early Mammalian Embryogenesismentioning

confidence: 99%

Quantitative developmental biology in vitro using micropatterning

Blin

2021

Development

View full text Add to dashboard Cite

Micropatterning encompasses a set of methods aimed at precisely controlling the spatial distribution of molecules onto the surface of materials. Biologists have borrowed the idea and adapted these methods, originally developed for electronics, to impose physical constraints on biological systems with the aim of addressing fundamental questions across biological scales from molecules to multicellular systems. Here, I approach this topic from a developmental biologist's perspective focusing specifically on how and why micropatterning has gained in popularity within the developmental biology community in recent years. Overall, this Primer provides a concise overview of how micropatterns are used to study developmental processes and emphasises how micropatterns are a useful addition to the developmental biologist’s toolbox.

show abstract

“…The high rates of false-positive diagnoses will often lead to disposal of embryos with entirely normal implantation/pregnancy potential. Moreover, human embryos ability for self-correction mechanisms [ 8 , 12 – 14 ], together with known chromosomal mosaicism, a common feature of early human embryos development [ 15 ], reinforce the crucial need for prenatal diagnosis (by either chorionic villi sampling or amniocentesis) in PGT pregnancies, to validate the molecular PGT results of the growing embryo.…”

Section: Discussionmentioning

confidence: 99%

Can expelled cells/debris from a developing embryo be used for PGT?

et al. 2021

View full text Add to dashboard Cite

Background Preimplantation genetic testing (PGT) is offered to a wide range of structural and numerical chromosomal imbalances, with PGT- polymerase chain reaction (PCR), as the method of choice for amplifying the small DNA content achieved from the blastomere biopsy or trophectoderm (TE) biopsy, that might have a detrimental impact on embryonic implantation potential. Since human embryos cultured until Day-5–6 were noticed to expel cell debris/ fragments within the zona pellucida, we aimed to examine whether these cell debris/ fragments might be used for PGT, as an alternative to embryo biopsy. Methods Blastocysts, which their Day-3 blastomere biopsy revealed an affected embryo with single-gene defect, and following hatching leaved cell debris/fragments within the zona pellucida were analyzed. Each blastocyst and its corresponding cell debris/fragments were separated and underwent the same molecular analysis, based on multiplex PCR programs designed for haplotyping using informative microsatellites markers. The main outcome measure was the intra-embryo congruity of Day-3 blastomere biopsy and its corresponding blastocyst and cell debris/fragments. Results Fourteen affected embryos from 9 women were included. Only 8/14 (57.2%) of embryos demonstrated congruent molecular genetic results between Day-3 embryo and its corresponding blastocyst and cell debris/fragments. In additional 6/14 (42.8%) embryos, molecular results of the Day-3 embryos and their corresponding blastocysts were congruent, while the cell debris/fragments yielded no molecular diagnoses (incomplete diagnoses). Conclusions It might be therefore concluded, that in PGT cycles, examining the cell debris/fragments on Day-4, instead of Day-3 blastomere or Day-5 TE biopsies, is feasible and might avoid embryo biopsy with its consequent detrimental effect on embryos’ implantation potential. Whenever the latter results in incomplete diagnosis, TE biopsy should be carried out on Day-5 for final genetic results. Further large well-designed studies are required to validate the aforementioned PGT platform.

show abstract

Depletion of aneuploid cells in human embryos and gastruloids

Cited by 104 publications

References 45 publications

From contemplation to classification of chromosomal mosaicism in human preimplantation embryos

From contemplation to classification of chromosomal mosaicism in human preimplantation embryos

Quantitative developmental biology in vitro using micropatterning

Can expelled cells/debris from a developing embryo be used for PGT?

Contact Info

Product

Resources

About