Interferon-tau promotes luteal endothelial cell survival and inhibits specific luteolytic genes in bovine corpus luteum

<jats:p>Interferon-tau (IFNT), a maternal recognition of pregnancy (MRP) signals in domestic ruminants, suppresses the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (<jats:italic>STAT1</jats:italic>, <jats:italic>STAT2</jats:italic> and <jats:italic>IRF9</jats:italic>) and interferon-stimulated genes (ISGs: <jats:italic>MX2</jats:italic>, <jats:italic>ISG15</jats:italic> and <jats:italic>OAS1Y</jats:italic>) in both models. Furthermore, IFNT time-dependently induced STAT1 phosphorylation in LECs without affecting total STAT1. roIFNT-stimulated viable LECs numbers and the knockdown of protein inhibitor of activated STAT1 (PIAS1) abolished this effect, suggesting that PIAS1 may mediate the proliferative effect of IFNT. IFNT significantly downregulated luteolytic genes such as <jats:italic>TGFB1</jats:italic>, thrombospondin-1 (<jats:italic>THBS1</jats:italic>), endothelin-1 (<jats:italic>EDN1</jats:italic>) and serpin family E member-1 (<jats:italic>SERPINE1</jats:italic>) in LECs. However, less robust effects were observed in luteal slices. Moreover, PGF2a alone induced <jats:italic>THBS1</jats:italic>, <jats:italic>SERPINE1</jats:italic> and <jats:italic>EDN1</jats:italic> mRNA in CL slices whereas in the presence of IFNT, <jats:italic>THBS1</jats:italic> and <jats:italic>SERPINE1</jats:italic> stimulation was abolished. Collectively, these results indicate that IFNT acts via STAT1- IRF9-dependent and independent pathways and affects diverse luteal functions. Most interestingly, this study suggests the existence of an anti-luteolytic effect of IFNT in bovine CL, namely, inhibiting key PGF2a-induced luteolytic genes. The proliferative effect of IFNT may constitute an additional mechanism that promotes luteal cell survival, thus, extending the luteal life span during early pregnancy in cows.</jats:p>