The role of miRNAs in the evolution of mammal implantation.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The embyros of all therian mammals (marsupials and eutheria) must undergo implantation for successful pregnancy to occur but the process has diversified significantly across lineages. The majority of pregnancy loss occurs around this time and is when life-course health can be determined. The goal of this proposal is to achieve molecular-level understanding of the origin and diversification of implantation strategies across mammals. To achieve this we are focussing on a set of microRNA (miRNA) genes whose origins are co-incident with the origin of mammals and how they mediate implantation in eutherian mammals. MiRNAs are endogenous RNAs that carry out posttranscriptional repression or decay of protein-coding mRNA and lncRNAs and they play a pervasive role in regulating key processes such as cellular processes of proliferation, differentiation and apoptosis. MiRNAs have been tightly associated with the evolution of complexity. We have already identified a subset of 17 out of a total of 54 miRNA genes that emerged coincident with the origin of therian mammals and to our knowledge were never subsequently lost. Most recently we have shown some are regulated by molecular cues important for endometrial receptivity to implantation. We have established that these miRNA genes are predicted to target genes that (i) have undergone positive selection, and (ii) gained uterine expression on the stem lineage.
Our key research questions are:
1. What are the conservation and divergence patterns of miRNA genes that arose at the origin of placental mammals?
2. What are the targets of the conserved miRNAs and how have they changed across mammals?
3. Do changes in miRNA repertoire tally with observed implantation and placental phenotypic variation through time?
4. What are the functions and mechanisms of action of miRNAs in diverse implantation strategies in placental mammals?