scholarly journals Early Pregnancy Induces Expression of STAT1, OAS1 and CXCL10 in Ovine Spleen

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 882 ◽  
Author(s):  
Yujiao Wang ◽  
Xu Han ◽  
Leying Zhang ◽  
Nan Cao ◽  
Lidong Cao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Early Pregnancy ◽  
Oligoadenylate Synthetase ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Adaptive Immune ◽  
Ruminant Species ◽  
Immunohistochemistry Analysis ◽  
Stat1 Protein ◽  
Red Pulp

Interferon-tau is a maternal recognition factor in ruminant species, and spleen plays an essential role in regulating innate and adaptive immune responses. However, it is not fully understood that early pregnancy induces expression of interferon stimulated genes (ISGs) in the spleen during early pregnancy in ewes. In this study, spleens were collected from ewes at day 16 of the estrous cycle, and on days 13, 16, and 25 of gestation (n = 6 for each group), and RT-qPCR, western blot and immunohistochemistry analysis were used to detect the expression of signal transducer and activator of transcription 1 (STAT1), 2′,5′-oligoadenylate synthetase 1 (OAS1), myxovirusresistance protein 1 (Mx1) and C-X-C motif chemokine 10 (CXCL10). The results revealed that STAT1, OAS1 and CXCL10 mRNA and proteins were upregulated in the spleens during early pregnancy, and STAT1 protein was located in connective tissue cells in the capsule and trabeculae, and blood cells and lymphocytes in the red pulp. However, early pregnancy had no significant effects on expression of MX1 mRNA and protein. In conclusion, early pregnancy induces expression of STAT1, OAS1 and CXCL10 in maternal spleen, suggesting that maternal spleen is involved in immune regulation of pregnancy in sheep.

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

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Raghavendra Basavaraja ◽  
Senasige Thilina Madusanka ◽  
Jessica N. Drum ◽  
Ketan Shrestha ◽  
Svetlana Farberov ◽  
...  
Keyword(s):  
Cell Viability ◽  
Granulosa Cells ◽  
Early Pregnancy ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Interferon Tau ◽  
Cell Counts ◽  
Domestic Ruminants ◽  
Stat1 Protein

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.

scholarly journals Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype

2016 ◽  
Vol 113 (38) ◽  
pp. 10678-10683 ◽  
Author(s):  
Aryn A. Price ◽  
Dana Tedesco ◽  
Mona R. Prasad ◽  
Kimberly A. Workowski ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Gene Signature ◽  
Innate Immune ◽  
Signaling Proteins ◽  
Peripheral Blood Mononuclear ◽  
Interferon Stimulated Genes ◽  
Adaptive Immune ◽  
Antiviral Genes ◽  
Antiviral Gene

Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14+ cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype.

Pregnancy-induced changes in the transcriptome of the bovine corpus luteum during and after embryonic interferon-tau secretion

2021 ◽  
Author(s):  
Megan A Mezera ◽  
Wenli Li ◽  
Milo C Wiltbank
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Early Pregnancy ◽  
Practical Importance ◽  
Interferon Signaling ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Bovine Corpus Luteum ◽  
Major Alteration ◽  
Induced Changes

Abstract Understanding luteal maintenance during early pregnancy is of substantial biological and practical importance. Characterizing effects of early pregnancy, however, has historically been confounded by use of controls with potential exposure to early PGF pulses or differences in CL age. To avoid this, the present study utilized bihourly blood sampling to ensure control CL (n = 6) were of a similar age to CL from pregnant animals (n = 5), yet without exposure to PGF pulses. Additionally, CL from second month of pregnancy (n = 4) were analyzed to track fate of altered genes after cessation of embryonic interferon tau (IFNT) secretion. The major alteration in gene expression in first month of pregnancy occurred in interferon-stimulated genes (ISGs), with immune/interferon signaling pathways enriched in three independent over-representation analyses. Most ISGs decreased during second month of pregnancy, though, surprisingly, some ISGs remained elevated in the second month even after cessation of IFNT secretion. Investigation of luteolytic genes found few altered transcripts, in contrast to previous reports, likely due to removal of controls exposed to PGF pulses. An exception to this trend was decreased expression of transcription factor NR4A1. Beyond luteolytic genes and ISGs, over representation analyses highlighted the prevalence of altered genes within the extracellular matrix and regulation of IGF availability, confirming results of other studies independent of luteolytic genes. These results support the idea that CL maintenance in early pregnancy is related to lack of PGF exposure, although potential roles for CL expression of diverse ISGs and other pathways activated during early pregnancy remain undefined.

Production of interferon by red deer (Cervus elaphus) conceptuses and the effects of roIFN-tau on the timing of luteolysis and the success of asynchronous embryo transfer

Reproduction ◽  
2000 ◽  
pp. 387-395 ◽  
Author(s):  
KJ Demmers ◽  
HN Jabbour ◽  
DW Deakin ◽  
AP Flint
Keyword(s):  
Embryo Transfer ◽  
Early Pregnancy ◽  
Cervus Elaphus ◽  
Pregnancy Loss ◽  
Red Deer ◽  
Interferon Tau ◽  
Recombinant Interferon ◽  
Uterine Flushing ◽  
Calving Rate

The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.

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