Interferon tau: a novel pregnancy recognition signal.
OBJECTIVE
Trophectoderm of ruminant conceptuses (embryo and associated membranes) secretes tau interferons (IFNtau) as the pregnancy recognition signal. How does it act?


METHODS
Review of current data.


RESULTS
IFNtau 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 F2alpha, 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 IFNtau on days 12-15 for sheep and days 14-17 for cows and goats is essential for pregnancy recognition.


CONCLUSIONS
We propose that IFNtau affects endometrial gene expression by activating the Jak/Stat pathway, which results in formation of the ISGF3alpha transcription factor complex. ISGF3alpha 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 roIFNtau) 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 IFNtau-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.
Bazer
F W
FW
Department of Animal Science and Center for Animal Biotechnology, Texas A&M University, College Station 77843-2471, USA.
Spencer
T E
TE
Ott
T L
TL
D000818:Animals; D002417:Cattle / Q000502:physiology; D003338:Corpus Luteum / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004717:Endometrium / Q000378:metabolism; D004971:Estrus; D005260:Female; D005786:Gene Expression Regulation; D006041:Goats / Q000502:physiology; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D050832:Interferon-Stimulated Gene Factor 3; D050833:Interferon-Stimulated Gene Factor 3, alpha Subunit; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011270:Pregnancy, Animal / Q000502:physiology*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D012418:Ruminants / Q000502:physiology*; D012756:Sheep / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050833:Interferon-Stimulated Gene Factor 3, alpha Subunit; D011257:Pregnancy Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; C020947:interferon tau