ArticleeLife2024
Complex aneuploidy triggers autophagy and p53-mediated apoptosis and impairs the second lineage segregation in human preimplantation embryos.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- Embryo quality control via lineage-specific aneuploid cell elimination in embryos and stem cell-derived embryo models.Nature communications · 2026Article
- Abnormal cleavage patterns in equine in vitro-produced embryos lead to higher early pregnancy loss.Equine veterinary journal · 2026Article
- Morphogen Gradients as Drivers of Mosaicism During Early Human Development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Introducing the Blastocyst Fragmentation Indicator (BFI): A Novel Time-Lapse Metric for Enhanced Aneuploidy Risk Stratification in Non-Invasive Embryo Assessment.JBRA assisted reproduction · 2026Article
- The role of mitochondrial DNA copy number in spent culture medium in predicting outcomes of single blastocyst transfer.Journal of assisted reproduction and genetics · 2025Article
- Cell competition eliminates aneuploid human pluripotent stem cells.Stem cell reports · 2025Article
- Case report: re-biopsy rescues a to-be-discarded segmental aneuploid embryo resulting in a healthy pregnancy with normal prenatal testing results.Journal of assisted reproduction and genetics · 2025Article
- Correlation among blastocoel fluid DNA level, apoptotic genes expression and preimplantation aneuploidy.Reproduction & fertility · 2025Article
- Article
- Non-invasively predicting euploidy in human blastocysts via quantitative 3D morphology measurement: a retrospective cohort study.Reproductive biology and endocrinology : RB&E · 2024Article
- Multinucleation in the Human Embryo's First Mitosis: Linking Spindle Geometry Defects, SAC Tolerance, Chromosome Segregation, and Nuclear Envelope Reassembly.Reproductive medicine and biologyReview
- Morphokinetic Markers of Blastocyst Formation and Chromosomal Euploidy in Embryos Derived From In Vitro Maturation Oocytes.Reproductive medicine and biologyArticle
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
About 70% of human cleavage stage embryos show chromosomal mosaicism, falling to 20% in blastocysts. Chromosomally mosaic human blastocysts can implant and lead to healthy new-borns with normal karyotypes. Studies in mouse embryos and human gastruloids showed that aneuploid cells are eliminated from the epiblast by p53-mediated apoptosis while being tolerated in the trophectoderm. These observations suggest a selective loss of aneuploid cells from human embryos, but the underlying mechanisms are not yet fully understood. Here, we investigated the cellular consequences of aneuploidy in a total of 125 human blastocysts. RNA-sequencing of trophectoderm cells showed activated p53 pathway and apoptosis proportionate to the level of chromosomal imbalance. Immunostaining corroborated that aneuploidy triggers proteotoxic stress, autophagy, p53-signaling, and apoptosis independent from DNA damage. Total cell numbers were lower in aneuploid embryos, due to a decline both in trophectoderm and in epiblast/primitive endoderm cell numbers. While lower cell numbers in trophectoderm may be attributed to apoptosis, aneuploidy impaired the second lineage segregation, particularly primitive endoderm formation. This might be reinforced by retention of NANOG. Our findings might explain why fully aneuploid embryos fail to further develop and we hypothesize that the same mechanisms lead to the removal of aneuploid cells from mosaic embryos.
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Registered trials
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