Embryo–Uterine Cross-Talk: Exploration of the Immunomodulatory Mechanism in Buffalo

SIMPLE SUMMARY: Early embryonic loss is the major cause of repeat breeding in buffalo. For successful pregnancy outcomes, proper communication between the embryo and maternal system is very important. When the embryo reaches the uterus, being semi-allogenic in origin, it has to cope from maternal immune reactions to further survive. To survive better in the maternal system, proper embryo functioning is important to give proper signals to the maternal system, and at the same time, an adequate conducive maternal environment is also required for embryonic survival. It was found that blastocyst-stage embryos release some specific molecules (such as interferon-tau), which act as signals to the maternal endometrium. To this response, several genes are modulated in the maternal system and affect expression of several genes in the embryo as well. This way, the embryo survives in the maternal system, and pregnancy continues. ABSTRACT: Understanding the molecular cross-talk between the embryo and uterine endometrium is crucial for the improvement of IVF outcomes. The present work was undertaken to investigate the effect of pre-implantation embryo on the expression profile of immune-related genes in uterine epithelial cells (UECs) and PBMCs in buffalo. UECs were isolated from slaughterhouse-derived non-gravid uteri, cultured ex vivo and characterized, and buffalo embryos were produced in vitro from slaughterhouse-derived ovaries. Embryos co-cultured with steroid-treated UECs significantly stimulated (p < 0.05) the relative mRNA abundance of PTGS2, ISG15, OAS1, MX2, IFNAR1 and IFNAR2 in UECs while they significantly suppressed the mRNA expression of NFkβIA, NFkβ2, TNFα and IL1B, with no significant change in TGFβ1 and IL10 in the co-culture of embryos with UECs. In vitro treatment of PBMCs with conditioned media (CM) derived from embryos as well as UEC–embryo co-culture upregulated the mRNA abundance of ISG15, TGFβ1, PTGS2OAS1, MX2 and STAT1 while it downregulated IL17 and TNFα expression. The expression of IFNAR1 and IFNAR2 was elevated in PBMCs cultured in embryo-derived CM, but there was no significant change in PBMCs cultured in UEC–embryo co-culture CM. Thus, it can be concluded that the developing embryo and its secretions modulate the expression of immune responses by inducing an anti-inflammatory action in uterine epithelial cells for acceptance of the semi-allogenic embryo in the uterus to sustain pregnancy in buffalo.