Regulation of conceptus interferon-tau gene subtypes expressed in the uterus during the peri-implantation period of cattle

Conceptus interferon tau (IFNT), produced by the embryonic trophectoderm, is known as a major signaling protein essential for the process of maternal recognition of pregnancy in ruminants. Similar to other IFN gene families such as IFNA and IFNB, multiple IFNT genes exist. The number of IFNT genes actively transcribed and regulated in conceptuses of cattle has, however, not been well characterized. In this study, IFNT transcripts in utero were studied through the use of next generation sequencer. Among 38 IFN genes registered and eight annotated as IFNT, only two transcripts, IFNT1 and IFNTc1, were found in conceptuses in utero. Relative abundance of transcription factor(s) involved in the regulation of IFNT genes were investigated by real-time PCR. Transcriptional activity of IFNT1 and IFNTc1 were investigated using bovine non-trophoblast ear fibroblast (EF) cells, which were co-transfected with luciferase reporter constructs with upstream (−631 to −51) promoter regions of IFNT1 or IFNTc1 and various transcription factor expression plasmids, CDX2, AP1 (JUN), ETS2 and/or CREBBP. CDX2 with AP1 and ETS2 was found to increase luciferase activity of IFNT1 and IFNTc1 approximately 14- and 11-fold, respectively, in EF cells, which do not express the CDX2 gene. These results indicated that two isoforms of conceptus IFNT genes of cattle could be regulated differently in utero. Furthermore, IFNT1 and IFNTc1 were found to have similar antiviral activity, suggesting that both IFNT genes could function to increase conceptus signaling to the uterine endometrium for the process of maternal recognition of pregnancy during the pre-implantation period.