Intrauterine exosomes are required for bovine conceptus implantation.

Exosomes, extracellular vesicles, are present in uterine flushing fluids (UFs), which are involved in conceptus-endometrial interactions during peri-implantation periods. Despite several studies on intrauterine exosomes conducted, the roles conceptus and endometrial exosomes play during peri-implantation periods have not been well characterized. To investigate the effect of bovine intrauterine exosomes on conceptus implantation, exosomes isolated from bovine UFs during peri-implantation periods were subjected to global protein analysis. The analysis detected 596 exosomal proteins, including ruminants' pregnancy recognition factor IFNT, and 172 differentially expressed proteins with more than 1.5-fold changes in UFs on days 17, 20 and 22 pregnancy (day of conceptus implantation is initiated on days 19-19.5). Treatment of primary bovine endometrial epithelial cells with exosomes from day 17 UFs up-regulated the expression of apoptosis-related genes, and treatment with exosomes from day 20 and 22 UFs up-regulated the expression of adhesion molecule. Based on these findings, intrauterine exosomes should be considered as an essential constituent for successful implantation.