Mechanism of action of interferon-tau in the uterus during early pregnancy

Early pregnancy is maintained in ruminants through the actions of conceptus -derived interferon (IFN)-tau on the endometrium. IFN-tau alters uterine re lease of PGF(2 alpha), which results in rescue of the corpus luteum and con tinued release of progesterone. The mechanism of action of IFN-tau includes inhibition of oestradiol receptors, consequent reduction in oxytocin recep tors, activation of a cyclooxygenase inhibitor, and a shift in the PGs to f avour PGE(2) over PGF(2 alpha). IFN-tau also induces several endometrial pr oteins that may be critical for survival of the developing embryo. One endo metrial protein induced by pregnancy and IFN-tau has been identified as bov ine granulocyte chemotactic protein-2 (bGCP-2). This chemotactic cytokine ( chemokine) has been used as a marker to delineate IFN-tau from IFN-alpha re sponses in the endometrium. A second protein, called ubiquitin cross-reacti ve protein (UCRP), resembles a tandem ubiquitin repeat. UCRP becomes conjug ated to cytosolic endometrial proteins in response to IFN-tau and pregnancy Proteins conjugated to UCRP are either modulated or targeted for processin g through the proteasome. The action of IFN-tau is mediated by induction of signal transducer and activator of transcription 1 (STAT-1), STAT-2 and in terferon regulatory factor 1 (IRF-1) transcription factors. Induction of th ese transcription factors, the alpha chemokines and UCRP is the prelude to maternal recognition of pregnancy in ruminants.