Specific activation of embryonic IFNAR1 and endometrial IFNAR2 induced by embryonic IFN tau directs normal uterine fate for bovine early implantation

Interferon-tau (IFN tau), as an antiluteolytic factor secreted by trophoderm during the pregnancy of ruminants, actually functions by activating the IFN tau receptor 1 (IFNAR1) and IFN tau receptor 2 (IFNAR2). However, it has not been clearly understood how IFN tau-IFNAR cascade regulation processes between the embryo and uterine epithelial cells in ruminants. In this study, we found the expression and location of IFN tau in the bovine blastocysts from different production sources. IFN tau, IFNAR1 and IFNAR2 were all located in the tmphoblast cells of the blastocyst. However, the fluorescence intensity of IFNAR1 was consistent with that of IFN tau. Antagonizing the expressions of IFNAR1 and IFNAR2 in embryos and co-culture with endometrial epithelium cells (EECs) reduced the expressions of Integrin alpha v beta 3, WNT7A, and ISG15 in EECs. Knocking out IFNAR1 and IFNAR2 reduce the expressions of Integrin alpha v beta 3 and WNT7A in EECs, the deletion of IFNAR2 gene has a greater impact than that of IFNAR1 gene. IFNAR1(-)/IFNAR2(+) and IFNAR1(+)/IFNAR2(-) EECs were co-cultured with IW embryos, the expression of Integrin alpha v beta 3 was inhibited, and the inhibition of IFNAR1(+)/IFNAR2(-) was much stronger, and the expression of WNT7A was not inhibited. The expressions of Integrin alpha v beta 3 and WNT7A did not change significantly after IFNAR1(-)/IFNAR2(+) and IFNAR1(+)/IFNAR2(-) co-culture with PA embryos. All of these results strongly suggest that specific activation of embryonic IFNAR1 and endometrial IFNAR2 induced by embryonic IFN tau directs normal uterine preparation for bovine early implantation.