Human embryo live imaging reveals nuclear DNA shedding during blastocyst expansion and biopsy

• Published in: Cell Vol. 186; no. 15; pp. 3166 - 3181.e18
• Main Authors: Domingo-Muelas, Ana, Skory, Robin M., Moverley, Adam A., Ardestani, Goli, Pomp, Oz, Rubio, Carmen, Tetlak, Piotr, Hernandez, Blake, Rhon-Calderon, Eric A., Navarro-Sánchez, Luis, García-Pascual, Carmen M., Bissiere, Stephanie, Bartolomei, Marisa S., Sakkas, Denny, Simón, Carlos, Plachta, Nicolas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.07.2023
• Subjects: Aneuploidy; Animals; Biopsy - methods; Blastocyst; Embryo Implantation; Female; Genetic Testing - methods; human embryo; Humans; live imaging; Mice; Pregnancy; preimplantation; Preimplantation Diagnosis - methods; trophectoderm biopsy; live imaging; aneuploidy; trophectoderm biopsy; human embryo; preimplantation
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2023.06.003

Proper preimplantation development is essential to assemble a blastocyst capable of implantation. Live imaging has uncovered major events driving early development in mouse embryos; yet, studies in humans have been limited by restrictions on genetic manipulation and lack of imaging approaches. We have overcome this barrier by combining fluorescent dyes with live imaging to reveal the dynamics of chromosome segregation, compaction, polarization, blastocyst formation, and hatching in the human embryo. We also show that blastocyst expansion mechanically constrains trophectoderm cells, causing nuclear budding and DNA shedding into the cytoplasm. Furthermore, cells with lower perinuclear keratin levels are more prone to undergo DNA loss. Moreover, applying trophectoderm biopsy, a mechanical procedure performed clinically for genetic testing, increases DNA shedding. Thus, our work reveals distinct processes underlying human development compared with mouse and suggests that aneuploidies in human embryos may not only originate from chromosome segregation errors during mitosis but also from nuclear DNA shedding. [Display omitted] •Fluorescent dyes enable live imaging of human embryos without genetic manipulation•Live imaging reveals differences between human and mouse embryo morphogenesis•Blastocyst expansion causes trophectoderm cell nuclear budding and DNA shedding•Mechanical stress from blastocyst expansion or biopsy triggers nuclear DNA loss Live imaging of human embryos unveils differences from mouse development and reveals DNA shedding from trophectoderm cell nuclei associated with mechanical stress from blastocyst expansion and biopsy for preimplantation genetic testing.