Effects of the Estrous Cycle and Early Pregnancy on Uterine Expression of Mx Protein in Sheep (Ovis aries)1

Abstract

Conceptuses of ruminant ungulates produce large amounts of a type I interferon, interferon-tau (IFNtau), which is the signal for maternal recognition of pregnancy. Induction of cellular Mx proteins is an important component of the response to type I interferon in the immune system, but Mx regulation and function have not been studied in the uterus. This study examined temporal and spatial alterations in ovine uterine Mx expression during the cycle and early pregnancy using immunohistochemistry, in situ hybridization, and Northern and slot-blot analysis. Sheep uterine endometrium expressed a single approximately 2.5-kilobase Mx mRNA transcript that was detectable at all stages of the estrous cycle and early pregnancy examined. In cyclic ewes, mRNA abundance in endometrium increased from Day 1 to peak levels at Day 13 and then declined to Day 15. In pregnant ewes, steady-state levels of Mx mRNA were first detected above the level in cyclic ewes at Day 13 postmating, were greater than 10-fold higher at Day 15, and remained elevated at Day 19. Expression of Mx mRNA in the myometrium did not change during the estrous cycle but increased approximately 23-fold between Days 11 and 15 of pregnancy. Immunohistochemical and in situ hybridization analysis revealed a similar temporal pattern of Mx expression. In cyclic ewes, Mx protein and mRNA were initially localized to the luminal epithelium at Days 1 and 3, increased from Days 5 to 13, especially in the shallow uterine glands, and then declined at Day 15. Pregnancy resulted in up-regulation of Mx expression in the luminal and glandular epithelium, stroma, and myometrium. Punctate Mx immunostaining and Mx mRNA concentrations were greatest when progesterone production was maximal during the estrous cycle and were strongly up-regulated by the conceptus across the entire uterine wall. It is suggested that a cascade of induction of Mx gene expression proceeds from the luminal epithelium to the outer longitudinal myometrium and that transcriptional activation of the promoter may involve both soluble cytokines (i.e., IFNtau) and steroid hormones (i.e., progesterone).

Trophoblast interferon and pregnancy

“…Other endometrial cytokines induced by IFN-τ include bovine granulocyte chemotactic protein 2 (Hansen et al, 1999). In addition, IFN-τ induces the ubiquitin crossreactive protein or interferon-stimulated gene 17 product (ISG-17;Hansen et al, 1999), which controls cytosolic protein processing through the proteosome; osteopontin , which promotes cellcell attachment and may be involved in attachment of the blastocyst to the endometrial epithelial surface; and the antiviral Mx protein (Ott et al, 1998).…”

Interferon Stimulated Genes (Isgs): Novel Pregnancy Specific Biomarker In Buffaloes (Bubalus bubalis

“…The MX gene was known to be expressed in the uterus of pregnant cow, sheep, pig and mare 30,31 . In another study in pregnant ewes, the MX1 transcript levels was significantly upturned on days 15, remained consistent till days 23 and then declined on days 25-30 28 .…”

Developing a conceptual model of possible benefits of condensed tannins for ruminant production

“…Furthermore, because pregnancy recognition in ruminants is accomplished by production of large amounts of interferon-tau (IFN-τ) by the Tedeschi, Ramírez-Restrepo and Muir mononuclear trophectoderm of the blastocyst (i.e. days 12 to 14 of gestation; Stewart, 1992;Ott et al, 1998), DNA methylation might be associated with transcriptional differences in the mutual response to this pathway (Walker and Mitchell, 2013). Although the experimental evidence needs to be tested at physiologically relevant conditions, this provides a potential explanation of the CT and/or their conjugated metabolites in blood circulation to improve reproductive performance and offspring survival through transcriptional regulation of gene expression.…”