Developmental potential of aneuploid human embryos cultured beyond implantation

Marta N. Shahbazi, Tianren Wang, Xin Tao, Bailey A. T. Weatherbee, Li Sun, Yiping Zhan, Laura Keller, Gary D. Smith, Antonio Pellicer, Richard T. Scott (), Emre Seli () and Magdalena Zernicka-Goetz ()
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Marta N. Shahbazi: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience
Tianren Wang: Foundation for Embryonic Competence
Xin Tao: Foundation for Embryonic Competence
Bailey A. T. Weatherbee: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience
Li Sun: Foundation for Embryonic Competence
Yiping Zhan: Foundation for Embryonic Competence
Laura Keller: University of Michigan
Gary D. Smith: University of Michigan
Antonio Pellicer: University of Valencia, Department of Paediatrics, Obstetrics and Gynaecology
Richard T. Scott: Rutgers-Robert Wood Johnson Medical School, Department of Obstetrics, Gynaecology and Reproductive Science
Emre Seli: IVIRMA New Jersey
Magdalena Zernicka-Goetz: Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Aneuploidy, the presence of an abnormal number of chromosomes, is a major cause of early pregnancy loss in humans. Yet, the developmental consequences of specific aneuploidies remain unexplored. Here, we determine the extent of post-implantation development of human embryos bearing common aneuploidies using a recently established culture platform. We show that while trisomy 15 and trisomy 21 embryos develop similarly to euploid embryos, monosomy 21 embryos exhibit high rates of developmental arrest, and trisomy 16 embryos display a hypo-proliferation of the trophoblast, the tissue that forms the placenta. Using human trophoblast stem cells, we show that this phenotype can be mechanistically ascribed to increased levels of the cell adhesion protein E-CADHERIN, which lead to premature differentiation and cell cycle arrest. We identify three cases of mosaicism in embryos diagnosed as full aneuploid by pre-implantation genetic testing. Our results present the first detailed analysis of post-implantation development of aneuploid human embryos.

Date: 2020
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DOI: 10.1038/s41467-020-17764-7

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