Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells

• Published in: Scientific reports Vol. 9; no. 1; pp. 14682 - 11
• Main Authors: Basavaraja, Raghavendra, Madusanka, Senasige Thilina, Drum, Jessica N., Shrestha, Ketan, Farberov, Svetlana, Wiltbank, Milo C., Sartori, Roberto, Meidan, Rina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.10.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/2; 13/31; 38; 38/77; 38/90; 631/80/82/23; 692/163; 82; Animals; Apoptosis; Apoptosis - genetics; Bcl-x protein; Caspase; Caspase-3; Cattle; Cell death; Cell survival; Cell Survival - genetics; Cell viability; Corpus luteum; Corpus Luteum - growth & development; Corpus Luteum - metabolism; Domestic animals; Endometrium - growth & development; Endometrium - metabolism; Female; Fibroblast growth factor 2; Gene Expression Regulation - genetics; Granulosa cells; Granulosa Cells - metabolism; Humanities and Social Sciences; Interferon; Interferon Type I - genetics; Kinases; Luteal Cells - metabolism; Mcl-1 protein; multidisciplinary; Phosphorylation; Pregnancy; Pregnancy Proteins - genetics; Proteins; Science; Science (multidisciplinary); Sheep - genetics; Sheep - growth & development; Stat1 protein; Thrombospondin; XIAP protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-51152-6

Interferon-tau (IFNT), serves as a signal to maintain the corpus luteum (CL) during early pregnancy in domestic ruminants. We investigated here whether IFNT directly affects the function of luteinized bovine granulosa cells (LGCs), a model for large-luteal cells. Recombinant ovine IFNT (roIFNT) induced the IFN-stimulated genes (ISGs; MX2 , ISG15 , and OAS1Y ). IFNT induced a rapid and transient (15–45 min) phosphorylation of STAT1, while total STAT1 protein was higher only after 24 h. IFNT treatment elevated viable LGCs numbers and decreased dead/apoptotic cell counts. Consistent with these effects on cell viability, IFNT upregulated cell survival proteins (MCL1, BCL-xL, and XIAP) and reduced the levels of gamma-H2AX, cleaved caspase-3, and thrombospondin-2 (THBS2) implicated in apoptosis. Notably, IFNT reversed the actions of THBS1 on cell viability, XIAP, and cleaved caspase-3. Furthermore, roIFNT stimulated proangiogenic genes, including FGF2 , PDGFB , and PDGFAR . Corroborating the in vitro observations, CL collected from day 18 pregnant cows comprised higher ISGs together with elevated FGF2, PDGFB , and XIAP , compared with CL derived from day 18 cyclic cows. This study reveals that IFNT activates diverse pathways in LGCs, promoting survival and blood vessel stabilization while suppressing cell death signals. These mechanisms might contribute to CL maintenance during early pregnancy.