Pregnancy and interferon t regulate DDX58 and PLSCR1 in the ovine uterus during the peri-implantation period

Interferon ζ (IFNT), the pregnancy recognition signal in ruminants, abrogates the luteolytic mechanism for maintenance of the corpus luteum for production of progesterone (P₄). This study examined the expression of DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 (DDX58) and phospholipid scramblase 1 (PLSCR1) mRNAs in the ovine uterus as these genes were increased most in 2fTGH (STAT1 positive) cells by IFNT. The results of this study indicated that IFNT regulates expression of DDX58 and PLSCR1 mRNAs in the ovine uterus, which confirmed the results of the in vitro transcriptional profiling experiment with the 2fTGH (parental STAT1 positive) and U3A (STAT1 null) cell lines. Steady-state levels of DDX58 and PLSCR1 mRNAs increased in cells of the ovine uterus between days 12 and 20 of pregnancy, but not between days 10 and 16 of the estrous cycle. The expression of DDX58 and PLSCR1 mRNAs was greatest in endometrial stromal cells, but there was transient expression in uterine luminal and superficial glandular epithelial cells. P₄ alone did not induce expression of DDX58 and PLSCR1 mRNAs; however, intrauterine injections of IFNT did induce expression of DDX58 and PLSCR1 mRNAs in the endometria of nonpregnant ewes independent of effects of P₄. These results indicate that IFNT induces expression of DDX58 and PLSCR1 in ovine endometrial cells via the classical STAT1-mediated cell signaling pathway. Based on their known biological effects, DDX58 and PLSCR1 are IFN-stimulated genes, which may increase the antiviral status of cells of the pregnant uterus to protect against viral infection and/or enhance secretion of type I IFNs that inhibit viral replication.