Expression of Interferon (IFN)-Stimulated Genes in Extrauterine Tissues during Early Pregnancy in Sheep Is the Consequence of Endocrine IFN-τ Release from the Uterine Vein

Abstract

The ruminant conceptus synthesizes and secretes interferon (IFN)-tau, which presumably acts via an intrauterine paracrine mechanism to signal maternal recognition of pregnancy. The aims of this study were to determine whether IFN-stimulated genes (ISG) such as ISG15 and OAS-1 are differentially expressed in blood cells circulating in the uterus of ewes; whether extrauterine components of the reproductive tract such as the corpus luteum (CL) also express mRNA for these ISG, and whether antiviral activity is greater in uterine vein than in uterine artery during early pregnancy. The concentrations of mRNA for both ISG were significantly greater (P < 0.0001) in endometrium and jugular blood of 15-d pregnant ewes than in nonpregnant ewes. ISG15 and OAS-1 mRNA concentrations were also greater (P < 0.05) in CL from 15-d pregnant ewes than in nonpregnant ewes. Immunohistochemistry revealed intense staining for ISG15 in large luteal cells on d 15 of pregnancy. Blood cells from uterine artery and vein of 15-d pregnant ewes had similar ISG15 and OAS-1 mRNA concentrations, suggesting that these cells were not conditioned by IFN-tau within the uterus. By using an antiviral assay, uterine venous blood was found to contain 500- to 1000-fold higher concentrations of bioactive IFN-tau than in uterine arterial blood on d 15 of pregnancy. It is concluded that uterine vein releases IFN-tau, which induces ISG in extrauterine tissues such as the CL during the time of maternal recognition of pregnancy.

Upregulation of Interferon-stimulated Genes and Interleukin-10 in Peripheral Blood Immune Cells During Early Pregnancy in Dairy Cows

“…Oliveria et al [34] demonstrated greater antiviral activity in uterine vein blood from Day15 pregnant sheep. Additionally, Bott et al [35] showed that preadsorption of blood by IFNT antibody reduced this antiviral activity, suggesting the release of IFNT into the uterine vein during the MRP.…”

Função do interferon-tau durante o reconhecimento materno da gestação em ruminantes

“…Dados recentes reportam a expressão de ISGs no CL e em outros tecidos extrauterinos durante o início da prenhez em ovelhas, sugerindo uma ação endócrina do IFNT (OLIVEIRA et al, 2008). A ISG15 (gene estimulado por inteferon 15) é uma proteína que possui função semelhante a uma ubiquitina (AUSTIN et al, 1996) e é expressa no útero durante o início da gestação em resposta ao IFNT.…”

“…A ISG15 (gene estimulado por inteferon 15) é uma proteína que possui função semelhante a uma ubiquitina (AUSTIN et al, 1996) e é expressa no útero durante o início da gestação em resposta ao IFNT. Contudo, por meio de imunohistoquímica, sua presença foi também detectada em células luteais grandes do CL de ovelhas no dia 15 da gestação (OLIVEIRA et al, 2008). A ação endócrina do IFNT foi corroborada pela infusão de IFNT recombinante ovino (roIFNT), por sete dias, na veia uterina de ovelhas (BOTT et al, 2010).…”

“…Dentre os ISGs que aumentam sua expressão durante o início da gestação em resposta ao IFNT, estão o 2',5' oligoadenilato sintetase (OAS; MIRANDO et al, 1991;SCHMITT et al, 1993;JOHNSON et al, 2001), o gene de resistência ao myxovirus 1 (MX1; (OTT et al, 1998) e o gene estimulado pelo interferon 15 (ISG15; NAIVAR et al, 1995;AUSTIN et al, 1996;JOHNSON et al, 1999). Estudos recentes demonstraram a expressão de ISGs em células do sangue (YANKEY et al, 2001;HAN et al, 2006;GIFFORD et al, 2007) e CL (OLIVEIRA et al, 2008;BOTT et al, 2010) logo após a sinalização por IFNT no início da gestação em ruminantes.…”

Exogenous hormonal manipulation to increase reproductive efficiency in dairy cows

“…Mann and Lamming (1999) effects on the endometrium, but also effects on cells in other tissues (HICKS et al, 2003;GIFFORD, 2010). Interferon-τ exits the uterus and reaches the maternal circulation (Oliveira et al, 2008), which induces expression of genes in blood leukocytes (GIFFORD et al, 2008;OLIVEIRA et al, 2008). In fact, mRNA abundance for ISG in leukocytes parallels the VAN CLEEFF et al, 1996).…”