Dynamic of Interferon Signaling and Immune Regulation in the Bovine Endometrium During Successful and Failed Pregnancies

Abstract The regulation of endometrial–conceptus communication during early pregnancy and their association with pregnancy loss were investigated in beef cattle. Estrous cycles of heifers were synchronized, followed by either a SHAM procedure (n = 15) or embryo transfer (n = 71) on Day 7 (Day 1 = ovulation). Endometrial luminal epithelial cells were collected, and luteal function was assessed via Doppler ultrasonography on Days 6, 15, and 20. Animals were categorized into five groups (n = 6–8/group): Cycling (simulated embryo transfer), EL7-20, EL20-25, EL25-30 (embryo losses detected on Days 20, 25, or 30, respectively), and Pregnant (confirmed by Day 30). Endometrial ISG15 and RSAD2 expressions were upregulated in EL20-25, EL25-30, and Pregnant groups on Days 15 and 20, indicating conceptus-induced immune activation in heifers with maintained corpora lutea. IRF2 was downregulated on Day 15 in the EL25-30 and Pregnant group. On Day 20, IFNγ, IL6, and IL10 were upregulated in EL20-25, EL25-30 and Pregnant groups, reflecting immune modulation supportive of pregnancy, whereas IL1β and IL8 were increased only in EL20-25 and EL25-30 groups, indicating a pro-inflammatory state associated with pregnancy loss. TGFβ1 expression increased on Day 20 in Cycling and EL7-20 groups. TLR2 expression increased between Days 6 and 20 in Pregnant, EL20-25, and EL25-30 groups, while TLR4 was dysregulated across all groups except Pregnant. These findings indicate that the conceptus stimulates early immune activation—characterized by the induction of ISGs, IL6, IL10, IFNγ, and TLR2—by Day 15 in recipients with sustained luteal activity, independent of pregnancy outcomes. In contrast, dysregulated IL1β, IL8, and TLR4 expression is associated with early pregnancy failure.