Effects of endometrial embryokines on the preimplantation bovine embryo to create a gene expression signature consistent with a high competence phenotype†

Optimal embryonic development depends upon cell-signaling molecules released by the maternal reproductive tract called embryokines. The identity of specific embryokines that enhance the competence of the embryo for sustained survival is largely lacking. The current objective was to evaluate the effects of three putative embryokines in cattle on embryonic development to the blastocyst stage. The molecules tested were vascular endothelial growth factor A (VEGFA), C-X-C motif chemokine ligand 12 (CXCL12), and interleukin-6 (IL6). Molecules were added from day 4 to 7.5 of culture at 50 ng/mL (VEGFA and CXCL12) or 100 ng/mL (IL6). Endpoints were development to the blastocyst stage and transcript abundance for 94 specific genes involved in lineage commitment, epigenetic regulation, and other functions. Among the genes examined were eight whose transcript abundance has been related to embryo competence for survival after embryo transfer. None of the molecules increased the proportion of putative zygotes or cleaved embryos becoming blastocysts at day 7.5 of development. An embryo competence index based on a Bayesian multiple regression formula to weigh transcript abundance of the eight biomarker genes was not affected by treatment with VEGFA but was increased by both CXCL12 and IL6. The transcript abundance of 5 genes was modified by VEGFA, 19 by CXCL12, and 19 by IL6. A total of 11 genes were modified in a similar manner by CXCL12 and IL6. Most differentially expressed genes for CXCL12 and IL6 were downregulated, suggesting that the embryokines may promote a less energetically demanding metabolic state than would be the case in their absence.