Pregnancy and interferon tau regulate N-myc interactor in the ovine uterus

In ruminants, interferon tau (IFNT) is synthesized and secreted by the mononuclear trophectoderm cells of the conceptus and maintains the corpus luteum and its secretion of progesterone for successful implantation and maintenance of pregnancy. In this study, we examined regulation of the expression of N-myc interactor (NMI) gene by IFNT in the ovine uterus based on results of microarray data from a study that compared gene expression by human 2fTGH and U3A (STAT1-null 2fTGH) cell lines in response to treatment with IFNT or vehicle. In the present study, semiquantitative reverse transcription-polymerase chain reaction analyses verified that IFNT stimulated expression of NMI mRNA in 2fTGH (ie, in a STAT1-dependent manner), but not in U3A (STAT1-null) cells. Furthermore, results of western blot analyses indicated that immunoreactive NMI proteins in 2fTGH and U3A cell lines increased in a time-dependent manner only in response to IFNT. In ovine endometria, steady-state levels of NMI mRNA increased between days 14 and 16 of pregnancy and then decreased slightly by day 20, but there was no effect of day of the estrous cycle. Expression of NMI mRNA was most abundant in endometrial stromal cells, glandular epithelium, and conceptus trophectoderm. Intrauterine infusion of IFNT in cyclic ewes increased expression of NMI in the endometrium. Expression of NMI in ovine and bovine uterine cell lines increased in response to IFNT. Collectively, the results of the present study indicate that IFNT regulates expression of NMI mRNA and protein in ovine endometria during pregnancy via a STAT1-dependent cell signaling pathway.