Capturing aberrant cell behaviors producing defects in human embryos via live imaging.

Abstract

The generation of human embryos in vitro has revolutionized reproductive medicine, and also made it possible to study fundamental aspects of early human development. However, human preimplantation embryos often display an array of morphological defects associated with poor development and implantation. Here, we used live-embryo imaging and computational analysis to capture how these defects can be produced in real time. We record various forms of mitotic errors including lagging chromosomes producing micronuclei, multipolar spindles causing abnormal chromosome organization recapitulated by daughter cells, and uncontrolled scattering of condensed chromosomes. In addition, we capture abnormal cleavage furrow dynamics during cytokinesis producing binucleated and enucleated cells. Finally, we find cells with disrupted mitotic progression ultimately leading to blebbing and fragmentation. Thus, these results document specific aberrant cell behaviors producing morphological defects in real time, and indicate that errors during mitosis and cytokinesis represent a major cause of developmental failures in human embryos.