Regulators of human primitive endoderm formation

Most human embryos stop developing within days after fertilisation in the IVF clinic. This inefficiency
of human pre-implantation development is an obstacle to successful fertility treatments. Two
differentiation events in the pre-implantation embryo result in the formation of three lineages—
trophectoderm, epiblast, and primitive endoderm (PrE)— which prepare the early embryo for
implantation and development to term. Poor embryo development is not well understood.
Dysregulation of signalling pathways driving lineage differentiation may contribute to embryonic
developmental arrest and implantation failure. The molecular events guiding PrE differentiation in
humans remain elusive. We aim to investigate PrE formation which later contributes to the yolk sac.
We hypothesise that FGF and PDGF signalling are critical in PrE formation, especially in initiation,
specification, segregation and plasticity of PrE cells. To test this, we will assess the presence of
growth factors and their receptors in human embryos and generate knock-out FGFR1, FGFR4, and
PDGFR embryos to explore their roles in PrE development. Additionally, we will supplement different
growth factors and receptor inhibitors at specific stages. The embryos will be analysed using
morphokinetics, immunofluorescence, and single-cell RNA-sequencing. Insights into lineage
segregation and plasticity may enhance our understanding of early embryo loss and ultimately
improve IVF efficiency.