The interferon-tau (IFN-tau) are Type I IFN produced in trophectoderm of ruminants. They prevent the regression of the corpus luteum when a viable embryo is present in the uterus. The IFN-tau possess properties in common with other IFN, but their function in maternal recognition of pregnancy likely depends upon uncharacterized signal transduction pathways. IFN-tau have potential value as therapeutic agents as they reportedly exhibit broad cross-species reactivity and low cytotoxicity. Their genes are also not inducible by virus, and their expression is limited to trophectoderm prior to trophoblast attachment. Our goal is to determine how the IFN-tau differ from their close relatives in the way they initiate signaling and in their transcriptional control. There are nine aims: 1) To determine whether a recombinant IFN-tau is superior to an IFN-alpha and an IFN-omega as an antiluteolytic agent by comparing the three in their abilities to extend estrous cycle length in ewes. 2) To purify and characterize a membrane-associated protein from sheep endometrium that becomes cross-linked to IFN-tau but not to IFN- alpha. 3) To use the yeast two-hybrid screen to identify endometrial proteins that bind the cytoplasmic domain of the Type I receptor subunits. 4) To identify proteins that become rapidly phosphorylated in endometrium in response to IFN-tau, but not to IFN-alpha. 5) To compare the expression of Ets2 and Oct3/4, two transcription factors implicated in IFN-tau gene expression, in developing bovine embryos. 6) To identify co-activators that operate in association with Ets2. 7) By using the yeast single- hybrid screen, identify additional factors that transactivate IFN-tau genes. 8) To determine the mechanism whereby Oct3/4 inhibits the activation of IFN-tau genes by Ets2. 9) To utilize a recently developed bovine trophectoderm cell line to study trophectoderm function and IFN-tau expression. Together these studies will provide information on roles for IFN in non- pathogenic processes and insight into how trophectoderm differentiates during early embryonic development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD021896-15
Application #
6091040
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Yoshinaga, Koji
Project Start
1986-07-01
Project End
2005-04-30
Budget Start
2000-07-01
Budget End
2001-04-30
Support Year
15
Fiscal Year
2000
Total Cost
$261,000
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Ezashi, Toshihiko; Imakawa, Kazuhiko (2017) Transcriptional control of IFNT expression. Reproduction 154:F21-F31
Green, Mark P; Harvey, Alexandra J; Spate, Lee D et al. (2016) The effects of 2,4-dinitrophenol and d-glucose concentration on the development, sex ratio, and interferon-tau (IFNT) production of bovine blastocysts. Mol Reprod Dev 83:50-60
Gupta, Rangan; Ezashi, Toshihiko; Roberts, R Michael (2012) Squelching of ETS2 transactivation by POU5F1 silences the human chorionic gonadotropin CGA subunit gene in human choriocarcinoma and embryonic stem cells. Mol Endocrinol 26:859-72
Bermejo-Alvarez, Pablo; Rosenfeld, Cheryl S; Roberts, R Michael (2012) Effect of maternal obesity on estrous cyclicity, embryo development and blastocyst gene expression in a mouse model. Hum Reprod 27:3513-22
Bermejo-Alvarez, P; Roberts, R M; Rosenfeld, C S (2012) Effect of glucose concentration during in vitro culture of mouse embryos on development to blastocyst, success of embryo transfer, and litter sex ratio. Mol Reprod Dev 79:329-36
Ezashi, Toshihiko; Matsuyama, Haruyo; Telugu, Bhanu Prakash V L et al. (2011) Generation of colonies of induced trophoblast cells during standard reprogramming of porcine fibroblasts to induced pluripotent stem cells. Biol Reprod 85:779-87
Zhou, Liang; Wang, Wei; Liu, Yongqing et al. (2011) Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells 29:972-80
Schulz, Laura C; Roberts, R Michael (2011) Dynamic changes in leptin distribution in the progression from ovum to blastocyst of the pre-implantation mouse embryo. Reproduction 141:767-77
Roberts, R Michael; Fisher, Susan J (2011) Trophoblast stem cells. Biol Reprod 84:412-21
Roberts, R Michael; Katayama, Mika; Magnuson, Scott R et al. (2011) Transcript profiling of individual twin blastomeres derived by splitting two-cell stage murine embryos. Biol Reprod 84:487-94

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