Effects of the Estrous Cycle, Pregnancy, and Interferon Tau on 2′,5′-Oligoadenylate Synthetase Expression in the Ovine Uterus1

Abstract

The enzymes which comprise the 2',5'-oligoadenylate synthetase (OAS) family are interferon (IFN) stimulated genes which regulate ribonuclease L antiviral responses and may play additional roles in control of cellular growth and differentiation. This study characterized OAS expression in the endometrium of cyclic and pregnant ewes as well as determined effects of IFNtau and progesterone on OAS expression in cyclic or ovariectomized ewes and in endometrial epithelial and stromal cell lines. In cyclic ewes, low levels of OAS protein were detected in the endometrial stroma (S) and glandular epithelium (GE). In early pregnant ewes, OAS expression increased in the S and GE on Day 15. OAS expression in the lumenal epithelium (LE) was not detected in uteri from either cyclic or pregnant ewes. Intrauterine administration of IFNtau stimulated OAS expression in the S and GE, and this effect of IFNtau was dependent on progesterone. Ovine endometrial LE, GE, and S cell lines responded to IFNtau with induction of OAS proteins. In all three cell lines, the 40/46-kDa OAS forms were induced by IFNtau, whereas the 100-kDa OAS form appeared to be constitutively expressed and not affected by IFNtau. The 69/71-kDa OAS forms were induced by IFNtau in the S and GE cell lines, but not in the LE. Collectively, these results indicate that OAS expression in the endometrial S and GE of the early pregnant ovine uterus is directly regulated by IFNtau from conceptus and requires the presence of progesterone.

Senior Author Correspondence Information

“…Thus, OAS interaction with the PRL-R enhances PRL-mediated differentiated functions. Consistent with this observation, IFN-inducible OAS expression is correlated with increased Stat5-mediated differentiated functions in the pregnant ovine endometrium (Johnson et al, 2001). resulting in transcriptional activation of genes.…”

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

“…This study revealed that expression of enJSRV-Env mRNA by conceptus trophectoderm decreases between Days 13 and 16 of a normal pregnancy. This decline of enJSRV mRNA could result from active processing through recruitment and activation of antiviral ISGs such as Mx or 2 0 ,5 0 -oligoadenylate synthetase (OAS), which are known to be induced by IFNT (Johnson et al 2001. On the other hand, enJSRV-Env mRNA may accumulate under the influence of a regulatory feedback controlled by secretions from BNCs, which would account for the decline in enJSRV-Env mRNA around Day 16 as numbers of BNC increase.…”

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

“…Esses complexos se ligam a regiões definidas no DNA chamadas de elementos responsivos à estimulação por interferons (ISREs) que regulam a expressão de ISGs (HANSEN et al, 1999). 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.…”