Bovine Endometrium Drives and Responds to Divergence of In Vitro Produced Conceptus Biochemistry

In vitro produced (IVP) bovine embryos enhance herd genetics for important food production traits and support advanced reproductive technologies. However, less than 50% survive the first month of gestation after transfer to the surrogate. While the biochemical consequences of in vitro culture on the embryo before transfer have been well documented, less is known after transfer when the embryo interacts with the endometrium and pregnancy failure occurs. To investigate crosstalk between the IVP and in vivo derived (IVD) bovine conceptus and endometrium, a Day 16 conceptus-endometrial mono-culture and co-culture system was used, integrating transcriptomic and proteomic analyses. The IVP conceptus transcriptome (differentially expressed genes; DEG) diverged from the IVD conceptus but only after co-culture with endometrium (377 DEG; FDR < 0.05). Further, of the IVP conceptus DEG, 81 genes (21%) were associated with abnormal embryonic or fetal development. Significant biological processes associated with abundant endometrial DEG induced by IVP conceptuses were related to GTPase activity and the inflammatory response (FDR < 0.01), the latter of which may be associated with increased MHC class II expression, which was specific to IVP conceptuses. Proteomic analysis of culture media identified 1031 and 604 differentially abundant proteins (FDR < 0.05) associated with the IVD and IVP conceptus-endometrial co-cultures, respectively, compared to endometrium alone, indicating the proteomic environment surrounding the IVP conceptus may be suboptimal. Collectively, compared to the IVD conceptus, evidence suggests the endometrium drives and responds to divergence of IVP conceptus biochemistry, likely contributing to pregnancy failure.