Identifying causes of emergence of chromosomal abnormalities in human cleavage stage embryos.

Over fifty percent of human embryos obtained after in vitro
fertilization (IVF) show chromosomal abnormalities that arise after
fertilization during the first three cleavages and are therefore not
present in all cells of the embryo. This is considered the most
prominent cause of implantation failure and pregnancy loss both in
spontaneous conceptions and after IVF treatment. It remains unclear
why human embryos, in contrast to for instance mouse embryos,
show such extensive chromosomal abnormalities. We hypothesize
that chromosomal abnormalities in embryonic cells are caused by
insufficient functioning of mRNA or proteins involved in mitoses.
Furthermore, we suggest that this malfunctioning originates from a
shortage of these transcripts that is caused by unequal distribution of
the reserve maternal transcripts over the embryonic cells. Indeed,
during the first cleavages, the embryo is entirely dependent on the
reserves it receives from the oocyte, as it has not yet activated its
own genome. We will perform confocal live-imaging of human
embryos combined with groundbreaking spatial transcriptomics and
state-of-the-art single-cell omics to show for the first time the
relationship between insufficient mitoses due to low mRNA reserve
and chromosomal abnormalities in human embryos during the first
cell cleavages. With this project, we will yield novel insights on the
origin of chromosomal abnormalities in early human preimplantation
embryos.