Conserved conceptus-derived proteins elicit a species-specific response in the endometrium of species with different implantation strategies

Early embryo loss affects all mammalian species, including humans and agriculturally important food-producing mammals such as cattle. The developing conceptus (embryo and extra-embryonic membranes) secretes factors which modify the endometrium and can be critical for early pregnancy processes such maternal recognition of pregnancy (MRP) and enhancing uterine receptivity to implantation. For example, a competent bovine conceptus secretes IFNT to initiate MRP whereas the human blastocyst triggers MRP through the secretion of hCG. The bovine conceptus also secretes other proteins at the time of MRP, including CAPG, PDI, and PSAT1, which are highly conserved among placental mammals. I hypothesise that these proteins may be acting upon the endometrium to improve receptivity, embryo development, or implantation in species with different implantation strategies (humans and cattle).
This project utilises both standard and novel methods of in vitro endometrial cell culture to investigate how these conceptus-derived proteins alter the endometrium to potentially modulate early pregnancy success. Novel methods of culture includes both microfluidics (2D and 3D multicellular), organoids, and scaffold-based tissue culture to better model the endometrial environment and/or structure. Using these in vitro methods allows for the investigation of early pregnancy processes without the use of costly animal trials or ethical approval.
The results of this project demonstrate that the conceptus-derived proteins CAPG and PDI may be involved in modulating the endometrial transcriptional and translational secretome response to the conceptus to promote implantation and alter ULF composition in vivo, and PDI may have a direct role in controlling implantation. Additionally, key differences in response were observed when using different in vitro endometrial models, highlighting the need for more robust and in vivo like culture systems to study endometrial-conceptus interactions in vitro.