INTERFERON-TAU - A NOVEL PREGNANCY RECOGNITION SIGNAL

PROBLEM: Trophectoderm of ruminant conceptuses (embryo and associated membranes) secretes tan interferons (IFN tau) as the pregnancy recogni tion signal. How does it act? METHOD: Review of current data. RESULTS: IFNt acts on uterine epithelium to suppress transcription of the gene s for estrogen receptor and oxytocin receptor. This blocks development of the uterine luteolytic mechanism and, therefore, release of luteol ytic pulses of prostaglandin F-2 alpha, but it has no effect on expres sion of the progesterone receptor. Maintenance of progesterone secreti on by the corpus luteum ensures establishment and maintenance of pregn ancy. Secretion of IFN tau on days 12-15 for sheep and days 14-17 for cows and goats is essential for pregnancy recognition. CONCLUSION: We propose that IFN tau affects endometrial gene expression by activating the Jak/Stat pathway, which results in formation of the ISGF3 alpha t ranscription factor complex, ISGF3 alpha binds to interferon-stimulate d response elements and activates transcription of interferon-responsi ve 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 roIFN tau) results in a tr ansient increase in endometrial IRF-1 expression followed 36-48 hr lat er by a sustained increase in IRF-2. We propose that IRF-2, or an IFN tau-induced negative regulatory factor Like IRF-2, suppresses expressi on of the estrogen receptor gene and directly or indirectly blocks exp ression of the gene for oxytocin receptor to abrogate the uterine lute olytic mechanism and ensure the establishment of pregnancy.