CaltechAUTHORS
Published August 10, 2020 | Version Published + Supplemental Material
Journal Article Open

Developmental potential of aneuploid human embryos cultured beyond implantation

Creators

  • 1. ROR icon University of Cambridge
  • 2. ROR icon MRC Laboratory of Molecular Biology
  • 3. ROR icon University of Michigan–Ann Arbor
  • 4. ROR icon University of Valencia
  • 5. ROR icon Rutgers, The State University of New Jersey
  • 6. ROR icon Yale University
  • 7. ROR icon California Institute of Technology

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.

Additional Information

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 07 August 2019. Accepted 10 July 2020. Published 10 August 2020. M.N.S. is funded by the European Molecular Biology Organization (Advanced EMBO fellowship) and by the Medical Research Council (MRC, award MC_UP_1201/24). B.A.T.W. is a recipient of the Gates Cambridge Scholarship. Work in G.D.S. laboratory is funded by an American Society for Reproductive Medicine Research Institute Grant. Work in the M.Z.-G. laboratory is funded by a Wellcome Trust grant (207415/Z/17/Z), Open Philanthropy, Weston Havens, and Curci Foundations. These authors contributed equally: Marta N. Shahbazi, Tianren Wang, Xin Tao, Bailey A. T. Weatherbee. Author Contributions: M.N.S. helped design the study, performed human embryo, and stem cell experiments and wrote the paper. T.W. ad X.T. designed and performed the human embryo experiments and contributed to writing the paper. B.A.T.W. contributed to designing and performing the stem cell experiments and writing the paper. Y.Z. and L.S. performed the biostatistical analysis and contributed to writing the paper. L.K. and G.D.S. performed the embryonic stem cell derivations. A.P. contributed to the study design and paper. R.T.S., E.S., and M.Z.-G. designed and supervised the study, and wrote the paper. Data availability: All relevant data are available from the authors, with the exception of individual sequencing results that could lead to loss of anonymity for patients who donated their embryos. This is impermissible under approval of the Western Institutional Review Board and patient consents. Source data are provided with this paper. Code availability: The codes utilized for chromosome copy number analysis were compiled by the Foundation for Embryonic Competence (FEC), a not-for-profit entity that owns the intellectual property for genome amplification methodology and related analytical code. Competing interests. A.P. is shareholder of IVI-RMA and DIBIMED. E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence. The remaining authors declare no competing interests. Peer review information. Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Additional details

Identifiers

PMCID
PMC7418029
Eprint ID
104907
Resolver ID
CaltechAUTHORS:20200811-114715166

Funding

European Molecular Biology Organization (EMBO)
Medical Research Council (UK)
MC_UP_1201/24
University of Cambridge
Bill and Melinda Gates Foundation
American Society for Reproductive Medicine
Wellcome Trust
207415/Z/17/Z
Open Philanthropy
Weston Havens Foundation
Curci Foundation

Dates

Created
2020-08-11
Created from EPrint's datestamp field
Updated
2021-11-16
Created from EPrint's last_modified field

Caltech Custom Metadata

Caltech groups
Division of Biology and Biological Engineering (BBE)