Biological Roles of Interferon Tau (IFNT) and Type I IFN Receptors in Elongation of the Ovine Conceptus

Interferon tau (IFNT) is produced by the elongating conceptus in ruminants and is the maternal recognition of pregnancy signal. Available evidence supports the idea that IFNT acts in a paracrine and autocrine manner to modulate expression of genes in the endometrium and trophectoderm, respectively, which promote conceptus elongation. The actions of IFNT are mediated by the interferon (alpha and beta) receptor (IFNAR), which is comprised of two subunits, IFNAR1 and IFNAR2. To test the hypothesis that IFNT and its receptor have biological roles in conceptus elongation, an in vivo loss of function study was conducted by inhibiting IFNT or IFNAR1/2 mRNA translation in the trophectoderm of the ovine conceptus using morpholino antisense oligonucleotides (MAO) delivered via osmotic pumps from Days 8 to 14 post-mating. Elongating, filamentous type conceptuses were recovered from Day 14 ewes receiving a control morpholino or IFNAR MAOs. In contrast, severely growth-retarded and malformed conceptuses were recovered from IFNT MAO-infused ewes. Those conceptuses contained abnormal trophectoderm cells that were apoptotic based on TUNEL analyses. IFNT concentrations were reduced in the uterine lumen of IFNT MAO-infused ewes, as was the expression of classical Type I IFN-stimulated genes in the endometrium. IFNT concentrations were also lower in the uterine lumen of IFNAR1/2 MAO-infused ewes. These studies provide in vivo evidence that IFNT is a critical regulator of conceptus elongation and that its embryotrophic actions are primarily mediated by paracrine effects on the endometrium.