Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells
Abstract 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 (roI...
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Nature Portfolio
2019-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-019-51152-6 |
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| author | Raghavendra Basavaraja Senasige Thilina Madusanka Jessica N. Drum Ketan Shrestha Svetlana Farberov Milo C. Wiltbank Roberto Sartori Rina Meidan |
| author_facet | Raghavendra Basavaraja Senasige Thilina Madusanka Jessica N. Drum Ketan Shrestha Svetlana Farberov Milo C. Wiltbank Roberto Sartori Rina Meidan |
| author_sort | Raghavendra Basavaraja |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T21:32:06Z |
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| id | doaj.art-3326da401a86496fb5e8ca0ccc2b3ac7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:32:06Z |
| publishDate | 2019-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3326da401a86496fb5e8ca0ccc2b3ac72022-12-21T19:26:01ZengNature PortfolioScientific Reports2045-23222019-10-019111110.1038/s41598-019-51152-6Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa CellsRaghavendra Basavaraja0Senasige Thilina Madusanka1Jessica N. Drum2Ketan Shrestha3Svetlana Farberov4Milo C. Wiltbank5Roberto Sartori6Rina Meidan7Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemDepartment of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemDepartment of Animal Science, University of São PauloDepartment of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemDepartment of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemDepartment of Dairy Science, University of Wisconsin-MadisonDepartment of Animal Science, University of São PauloDepartment of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemAbstract 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.https://doi.org/10.1038/s41598-019-51152-6 |
| spellingShingle | Raghavendra Basavaraja Senasige Thilina Madusanka Jessica N. Drum Ketan Shrestha Svetlana Farberov Milo C. Wiltbank Roberto Sartori Rina Meidan Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells Scientific Reports |
| title | Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells |
| title_full | Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells |
| title_fullStr | Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells |
| title_full_unstemmed | Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells |
| title_short | Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells |
| title_sort | interferon tau exerts direct prosurvival and antiapoptotic actions in luteinized bovine granulosa cells |
| url | https://doi.org/10.1038/s41598-019-51152-6 |
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