Interferon tau: A novel pregnancy recognition signal

PROBLEM: Trophectoderm of ruminant conceptuses (embryo and associated membranes) secretes tau interferons (IFNτ) as the pregnancy recognition signal. How does it act? METHOD: Review of current data. RESULTS: IFNt acts on uterine epithelium to suppress transcription of the genes for estrogen receptor and oxytocin receptor. This blocks development of the uterine luteolytic mechanism and, therefore, release of luteolytic pulses of prostaglandin F(2α), but it has no effect on expression of the progesterone receptor. Maintenance of progesterone secretion by the corpus luteum ensures establishment and maintenance of pregnancy. Secretion of IFNτ on days 12-15 for sheep and days 14-17 for cows and goats is essential for pregnancy recognition. CONCLUSION: We propose that IFNτ affects endometrial gene expression by activating the Jak/Stat pathway, which results in formation of the ISGF3α transcription factor complex. ISGF3α binds to interferon-stimulated response elements and activates transcription of interferon-responsive genes such as interferon regulatory factor-1 (IRF-1) which, in turn, activates expression of the negative-acting transcription factor IRF-2. Pregnancy (or intrauterine injection of roIFNτ) results in a transient increase in endometrial IRF-1 expression followed 36-48 hr later by a sustained increase in IRF-2. We propose that IRF-2, or an IFNτ-induced negative regulatory factor like IRF-2, suppresses expression of the estrogen receptor gene and directly or indirectly blocks expression of the gene for oxytocin receptor to abrogate the uterine luteolytic mechanism and ensure the establishment of pregnancy.