Grant: Project Grant

Subfertility affects 1 in 6 couples and despite advances in assisted reproductive medicine (ART), our understanding of human embryo formation and infertility is limited. Accurate lineage specification is a key milestone for ensuring the healthy development of embryos. However, the precise mechanisms governing lineage specification in humans remain largely unknown. Small non-coding RNAs, particularly microRNAs (miRNAs), have been implicated in regulating various biological processes in embryos, including stem cell maintenance, however we lack a thorough understanding of their precise role in lineage specification. We have identified several differentially expressed miRNAs coinciding with the timing of the first lineage specification into trophectoderm (TE) and inner cell mass (ICM), many of which target components of the HIPPO signaling pathway or key genes known to be important in either self-renewal or differentation. The HIPPO pathway currently serves as the primary signaling mechanism lineage specification, and the miRNA-HIPPO network is increasingly recognized as an area of interest in cancer research, though this framework remains to be investigated in the embryo. We have also identified two key miRNA regulatory hotspots (C14MC and C19MC). While the role of C19MC is known to be a key factor in regulating the potential differentiation of trophoblast stem cells from naive or primed lines, the role of C14MC remains to be examined. Overall, this work will shed light onto the mechanism(s) underlying lineage segregation in the preimplantation embryo and pluripotency, an understudied area in the human. These data may potentially uncover a novel model of lineage regulation and are expected to make significant contributions to our understanding of early embryogenesis with ready translation to the clinic and stem cell biology.