A microarray analysis for genes regulated by interferon-τ in ovine luminal epithelial cells

Abstract

Interferon-t (IFNT) is released by preimplantation conceptuses of ruminant species and prepares the mother for pregnancy. Although one important function is to protect the corpus luteum from the luteolytic activity of prostaglandin-F 2a, IFNT most likely regulates a range of other physiological processes in endometrium. Here, an immortalized cell line from ovine uterine luminal epithelial cells was treated with IFNT for either 8 or 24 h. RNA was subjected to cDNA microarray analysis, with RNA from untreated cells as the reference standard. Of 15 634 genes, 1274 (8%) were IFNT responsive at P!0.01 and 585 at P!0.001 to at least one treatment. Of the latter, 356 were up-regulated and 229 down-regulated. Increasing IFNT concentrations from 10 ng/ml to 10 mg/ml had minor effects, and most genes up-or down-regulated at 8 h were regulated similarly at 24 h. Although IFNT influences many genes implicated in antiviral activity and apoptosis, its action also likely regulates prostaglandin metabolism, growth factors and their receptors, apoptosis and the nuclear factor (NF)-kB cascade, extracellular matrix accretion, angiogenesis, blood coagulation, and inflammation. In particular, it increased mRNA concentrations of genes related to the vascular endothelial growth factor R2 pathway of angiogenesis and down-regulated ones associated with hypoxia. Two genes implicated in the antiluteolytic actions of IFNT (encoding cyclooxygenase-2 and the oxytocin receptor respectively) were downregulated in response to all treatments. IFNT targets a complex range of physiological processes during the establishment of pregnancy. Reproduction (2007) 134 123-135

Bovine endometrial metallopeptidases MMP14 and MMP2 and the metallopeptidase inhibitor TIMP2 participate in maternal preparation of pregnancy

“…We furthermore performed in vitro experiments to examine whether the presence of early But interestingly and contrary to findings in sheep endometrium (Chen et al, 2007), a direct stimulation of recombinant interferon- did not affect TIMP2 gene expression in our bovine cell culture, indicating species specific peculiarities (Spencer et al, 2008). Thus, both the causing variable, most probably a factor secreted by the early embryo, and the purpose of the enhancement remain to be shown.…”

“…In sheep, interferon- has been shown to trigger the increase of TIMP2 (Chen et al, 2007;Gray et al, 2006), and TIMP2 mRNA expression has been shown to remain elevated in ovine and bovine early pregnancy (during Page 24 of 32 A c c e p t e d M a n u s c r i p t 17 implantation until day 31) (Ledgard et al, 2009). Because the increase in TIMP2 mRNA at day 18 was moderate in our study A, we confirmed the data using a second experimental set-up with identical twins from which one had received an embryo and the other a seminal plasma control insemination (Klein et al, 2006).…”

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

“…The SR cows with large conceptuses had reduced concentrations of TIMP2 and legumain protein in their gravid compared with non-gravid horns. In the case of TIMP2, it was not due to transcriptional differences despite indications from sheep that IFNT regulates TIMP2 expression (Gray et al 2006;Chen et al 2007). In addition, legumain protein concentrations have been reported to be reduced in the presence of larger conceptus with no differences in the mRNA expression (Ledgard et al 2009b).…”

Several fibroblast growth factors are expressed during pre-attachment bovine conceptus development and regulate interferon-tau expression from trophectoderm

“…Very little to no FGF10 is produced by luminal and glandular epithelium. Cell lines developed from ovine endometrial epithelium contain FGF10 mRNA (Chen et al 2007), but in situ studies did not detect FGF10 transcripts in luminal or glandular epithelium during diestrus and early pregnancy (Chen et al 2000). By contrast, FGF2 is produced by the endometrial epithelium and can be found in the uterine lumen during early pregnancy (Michael et al 2006, Ocon-Grove et al 2008.…”