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Depletion of aneuploid cells in human embryos and gastruloids.

Depletion of aneuploid cells in human embryos and gastruloids.

Authors :
Yang M
Rito T
Metzger J
Naftaly J
Soman R
Hu J
Albertini DF
Barad DH
Brivanlou AH
Gleicher N
Source :
Nature cell biology [Nat Cell Biol] 2021 Apr; Vol. 23 (4), pp. 314-321. Date of Electronic Publication: 2021 Apr 09.
Publication Year :
2021

Abstract

Chromosomal instability leading to aneuploidy is pervasive in early human embryos <superscript>1-3</superscript> and is considered as a major cause of infertility and pregnancy wastage <superscript>4,5</superscript> . Here we provide several lines of evidence that blastocysts containing aneuploid cells are worthy of in vitro fertilization transfer. First, we show clinically that aneuploid embryos can lead to healthy births, suggesting the presence of an in vivo mechanism to eliminate aneuploidy. Second, early development and cell specification modelled in micropatterned human 'gastruloids' grown in confined geometry show that aneuploid cells are depleted from embryonic germ layers, but not from extraembryonic tissue, by apoptosis in a bone morphogenetic protein 4 (BMP4)-dependent manner. Third, a small percentage of euploid cells rescues embryonic tissue in mosaic gastruloids when mixed with aneuploid cells. Finally, single-cell RNA-sequencing analysis of early human embryos revealed a decline of aneuploidy beginning on day 3. Our findings challenge two current dogmas: that a single trophectoderm biopsy at blastocyst stage to perform prenatal genetic testing can accurately determine the chromosomal make-up of a human embryo, and that aneuploid embryos should be withheld from embryo transfer in association with in vitro fertilization.

Details

Language :
English
ISSN :
1476-4679
Volume :
23
Issue :
4
Database :
MEDLINE
Journal :
Nature cell biology
Publication Type :
Academic Journal
Accession number :
33837289
Full Text :
https://doi.org/10.1038/s41556-021-00660-7