The maternal recognition of pregnancy in ruminants requires the production of interferons by the preimplantation blastocyst. These proteins, the trophoblast interferons (IFN-tau), are the products of a number of similar genes, the expression of which is controlled by characteristic promoter regions. They are expressed for a short period in high concentrations, and have antiluteolytic, antiviral, antiproliferative and immunomodulatory effects, through receptors on the endometrial epithelium. The antiluteolytic effects of IFN-tau result from inhibition of endometrial expression of the oxytocin receptor, through which circulating oxytocin stimulates episodic prostaglandin F2a production. Some of the properties of IFN-tau differ from those of other type I interferons, and they may have novel therapeutic effects. Because of their central role in early gestation, these proteins have excited the interest of reproductive physiologists. However, their other properties, and the fact that their expression is controlled so precisely, have made them of interest to a wide range of biologists.

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Trophoblast interferon and pregnancy.

IFN-tau: a novel subtype I IFN1. Structural characteristics, non-ubiquitous expression, structure-function relationships, a pregnancy hormonal embryonic signal and cross-species therapeutic potentialities.

Interferon-tau (IFN-tau), a type I IFN structurally related to IFN-alpha, is regarded as the major antiluteolytic factor secreted by the conceptus of ruminant ungulate species before definitive trophoblast attachment and implantation. It mediates its effects by acting on the uterine endometrium, where it blunts the normal pulsatile production of PGF2alpha, presumably as a result of its binding to type I IFN receptors. In this study, we describe the complementary DNAs for the two known subunits, IFNAR1 and IFNAR2, of this receptor isolated from bovine and ovine endometrial complementary DNA libraries by homology cloning. Although there is extensive inferred amino acid sequence similarity between bovine and ovine IFNAR1 (92% identity) and between bovine and ovine IFNAR2 (88% identity), they have diverged extensively from the human receptor subunits (approximately 67% and approximately 58% identity, respectively). Despite these differences in primary structure, the respective subunits from all three species are organized similarly in their extracellular and cytoplasmic regions, and the bovine and ovine subunits have each retained a number of polypeptide motifs implicated in signal transduction. These uterine receptors also appear not to be splice variants. The cloned ovine IFNAR1 subunit, for example, possesses the expected four extracellular SD100 domains of full-length bovine and huIFNAR1, and only the homologs of the so-called long form (huIFNAR2c) of human IFNAR2 have so far been identified. RT-PCR procedures indicate that the messenger RNA for both subunits are found, not only in endometrium, but in all other tissues examined except those ofpreimplantation conceptuses, which presumably cannot respond to the IFN-tau they produce. Quantitative RNase protection assays of ovine endometrial RNA show that the expression of neither subunit changes greatly during the estrous cycle or pregnancy. These data suggest that the type I IFN receptor, which is expressed by the endometrium and binds IFN-tau, is probably not a structurally unusual form.

Molecular cloning of ovine and bovine type I interferon receptor subunits from uteri, and endometrial expression of messenger ribonucleic acid for ovine receptors during the estrous cycle and pregnancy.

Trophoblast cells of ruminant placentas--A minireview.

Primary bovine chondrocytes were encapsulated in alginate and alginate combined with cartilage matrix extract, Cartrigel, for the purpose of cartilage tissue engineering. The cell constructs were incubated in vitro and gene expression of cartilage-specific extracellular matrix molecules was quantitated and localized with in situ hybridization with a decrease in expression observed in the alginate-Cartrigel constructs. Further understanding of cell response to scaffolds will allow rational design and development of hydrogels for cartilage tissue engineering.

Biological Response of Chondrocytes to Hydrogels

A sheep type I interferon receptor (oIFNAR1) cDNA was isolated from a lambda-ZAP library using a reverse transcription (RT)-PCR product probe generated from oestrous endometrial RNA. The oIFNAR1 cDNA was 79, 66 and 95% homologous to human, murine and bovine IFNAR1 cDNAs respectively. The encoded receptor was a 560-amino acid transmembrane protein 80, 66 and 95% similar to human, murine and bovine IFNAR1 respectively. Northern blot analysis of endometrial mRNA revealed the presence of 6.5, 4.3 and 3.7 kb transcripts. Using semi-quantitative RT-PCR the oIFNAR1 mRNA was not found to be down-regulated after 72 h treatment with bovine recombinant IFN-alpha I in in vitro experiments with endometrial explants.

P A Fisher

Papers

Structure of an ovine interferon receptor and its expression in endometrium.