Interferons as Hormones of Pregnancy*

Roberts, R. Michael; Cross, James C.; Leaman, Douglas W.

doi:10.1210/edrv-13-3-432

Cited by 164 publications

(138 citation statements)

References 169 publications

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“…The interferon-(IFN-) are type I IFN, structurally related to the IFN-␤, IFN-␣ and IFN-(with Ϸ25%, 50%, and 75% primary sequence identities, respectively) (1). Members of this multigene family are expressed within the first epithelium (trophectoderm) of the conceptuses of ruminant ungulate species (cattle, sheep, and their relatives) from the time that of blastocyst hatching to when the trophoblast attaches to the uterine wall.…”

mentioning

confidence: 99%

“…Members of this multigene family are expressed within the first epithelium (trophectoderm) of the conceptuses of ruminant ungulate species (cattle, sheep, and their relatives) from the time that of blastocyst hatching to when the trophoblast attaches to the uterine wall. Although exhibiting typical properties of other type I IFN, including an ability to induce an antiviral state in target cells expressing the type I IFN receptor, the function of the IFN-is that of preventing the regression of the corpus luteum, an event that normally occurs at the end of the estrous cycle when the animal is not pregnant (1,2). As a consequence, progesterone production is maintained, and the pregnancy can proceed.…”

mentioning

confidence: 99%

“…As a consequence, progesterone production is maintained, and the pregnancy can proceed. This ability of IFN-to extend corpus luteum lifespan is achieved indirectly by reducing the pulsatile output of the luteolytic factor, prostaglandin F 2␣ , from the uterine endometrium (1,2).…”

mentioning

confidence: 99%

“…Second, these genes are transcribed only within the embryonic trophectoderm (5,6). Third, expression of the IFNT is sustained over several days (1,(5)(6)(7) whereas expression of most other type I IFN genes usually occurs in response to virus or other pathogens and is short-lived (8).…”

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confidence: 99%

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Control of interferon-τ gene expression by Ets-2

Ezashi

Ealy

Ostrowski

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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112

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Expression of the multiple interferon-(IFN-) genes is restricted to embryonic trophectoderm of ruminant ungulate species for a few days in early pregnancy. The promoter regions of these genes are highly conserved. A proximal (bp ؊91 to ؊69) sequence has been implicated in controlling trophoblast-specific expression. Here it was used as a target for yeast one-hybrid screening of a day 13 conceptus cDNA library. Two transcription factors of the Ets family, Ets-2 and GABP␣, were identified, consistent with the observation that active ovine IFN-genes contain a single 10-bp Ets motif (core: GGAA) in the proximal segment, whereas three known inactive ovine genes contain a mutated core motif (TGAA). Cotransfection of a promoter-(؊126 to ؉50) luciferase reporter construct from an active gene (bovineIFN-1; boIFNT1) and an Ets-2 expression plasmid in human JAr cells provided up to a 30-fold increase in reporter expression, whereas promoters from inactive genes were not transactivated. GABP␣ alone was ineffective and had only a Ϸ2-fold positive effect when coexpressed with its partner GABP␤. Other Ets-related transcription factors, which were not detected in the genetic screen, also provided a range of lesser transactivation effects. Coexpression of Ets-2 and activated Ras failed to transactivate the IFNT promoter greater than Ets-2 alone in JAr cells. The presence of Ets-2 in nuclei of embryonic trophectoderm was confirmed immunocytochemically. Together, these data suggest that Ets-2 plays a role in the transient expression of the nonvirally inducible IFNT genes.

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Control of interferon-τ gene expression by Ets-2

Ezashi

Ealy

Ostrowski

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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112

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“…Type 1 IFNs comprise IFNA, IFNb, and IFNT and defense against infection by pathogens is considered to be the main function of this group (Roberts et al 1996, Spencer et al 2004. IFNT has sequence similarity (w50% amino acid identity) and functional homology to IFNA (Roberts et al 1992). All type 1 IFNs bind to common receptors such as IFNA receptor 1 (IFNA R1) and IFNA R2 (Li & Roberts 1994) and induce several common genes (Teixeira et al 1997, Staggs et al 1998, Hansen et al 1999, Asselin et al 2001, Choi et al 2001.…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Nitta¹,

Shirasuna²,

Haneda³

et al. 2011

Reproduction

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The corpus luteum (CL), which secretes large amounts of progesterone and is thus essential for establishing pregnancy, contains various types of immune cells that may play essential roles in CL function by generating immune responses. The lymphatic system is the second circulation system and is necessary for immune function, but the lymphatic system of the bovine CL has not been characterized in detail. We collected bovine CLs on days 12 and 16 of the estrous cycle (C12 and C16) and days 16 and 40 of early pregnancy (P16 and P40). Lymphatic endothelial hyaluronan receptor 1 (LYVE1) protein was detected in the CL by immunohistochemistry and western blotting and increased at P40 compared with C16. The mRNA expression levels of lymphangiogenic factors, such as vascular endothelial growth factor-C (VEGFC), VEGFD, and their common receptor VEGFR3, as well as the lymphatic endothelial cell (LyEC) marker podoplanin, increased in P16 and P40 CLs. Thus, it is suggested that the lymphatic system of the bovine CL reconstitutes during early pregnancy. Interferon tau (IFNT) from the conceptus in the uterus is a candidate for activating luteal lymphangiogenesis during the maternal recognition period (MRP). We found that treatment of LyECs isolated from internal iliac lymphatic vessels with IFNT stimulated LyEC proliferation and significantly increased mRNA expression of VEGFC and IFN-stimulated gene 15. Moreover, both IFNT and VEGFC induced LyECs to form capillary-like tubes in vitro.In conclusion, it is suggested that new lymphangiogenesis in the bovine CL begins during the MRP and that IFNT may mediate this novel phenomenon.

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ISG15‐dependent Regulation

Haas

2007

Protein Degradation Series

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Interferons as Hormones of Pregnancy*

Cited by 164 publications

References 169 publications

Control of interferon-τ gene expression by Ets-2

Control of interferon-τ gene expression by Ets-2

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

ISG15‐dependent Regulation

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