Grant: Project Grant

Subfertility affects 1 in 6 couples and despite advances in assisted reproductive medicine (ART), our understanding of human embryo health and infertility is limited. Embryonic development during the first week post-fertilization is arguably the most critical window. During this time, the first lineages are formed which give rise to the placenta and embryo proper. Successful formation of the first lineages is a developmental milestone required to ensure healthy embryo development. Currently, our knowledge pertaining to the mechanism(s) that control lineage segregation during human preimplantation development is lacking. Most of what we know about preimplantation development is extrapolated from studies using animal models and though they have provided a wealth of information, with recent advancements, it is clear that species differences exist. Therefore, findings must be carefully extrapolated to human development, highlighting the need for more studies directly in the human embryo. Further, miRNAs can regulate gene expression, and our recent work suggests that miRNAs are driving lineage specification in the embryo and that this is, at least in part, mediated by Hippo signaling. Hippo signaling is the current leading model for trophectoderm-inner cell mass specification. In the cancer field, miRNA-Hippo crosstalk is an emerging area of interest that remains to be explored in development. This proposal will determine, for the first time, the regulatory role of miRNAs and miRNA-Hippo crosstalk on lineage specification using a parallel model of human and mouse embryos. Further, this work will help us better understand the role of miRNA in embryo competence and their potential as predictive biomarkers in clinic. Overall, results from these studies are expected to make significant contributions to our understanding of early embryogenesis. I envision broad utility of this data in the fields of developmental, stem cells, and ART.