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Fuller W Bazer - One of the best experts on this subject based on the ideXlab platform.

  • Interferon Tau influences on growth and development of the conceptus
    Theriogenology, 2020
    Co-Authors: Fuller W Bazer, Heewon Seo, Greg A. Johnson
    Abstract:

    Interferon Tau (IFNT), the pregnancy recognition signal secreted from trophectoderm cells of ruminant conceptuses abrogates the uterine luteolytic mechanism to ensure maintenance of functional corpora lutea for production of progesterone (P4). Importantly, IFNT, in concert with P4, also induces expression of genes in uterine luminal (LE) and superficial glandular (sGE) epithelia for transport and/or secretion of histotroph into the uterine lumen to support growth and development of the conceptus. For example, IFNT and P4 induce transporters responsible foer transport of glucose and arginine into the uterine lumen during the peri-implantation period of pregnancy. Arginine activates the mechanistic target of rapamycin (MTOR) nutrient sensing cell signaling pathway to stimulate proliferation, migration, differentiation and translation of mRNAs essential for growth and development of the conceptus. Glucose not utilized by the conceptus is converted to fructose and those two hexose sugars are metabolized via aerobic glycolysis to produce metabolites used in the hexosamine biosynthesis pathway, pathways for one-carbon metabolism, and pentose phosphate pathway for synthesis of ribose sugars and NADPH. Arginine is metabolized to nitric oxide (NO) that stimulates angiogenesis in uterine and placental tissues, and to polyamines required for many cellular functions critical for growth and development of the conceptus. In summary, IFNT and P4 regulate expression of genes for transport of select nutrients into the pregnant uterus during the peri-implantation period of pregnancy. Those nutrients are then metabolized via multiple metabolic pathways to not only provide ATP, but also substrates for synthesis of nucleotides, amino acids, co-factors required for growth, development, and survival of conceptuses during the peri-implantation period of pregnancy.

  • Effects of catecholamines on secretion of Interferon Tau and expression of genes for synthesis of polyamines and apoptosis by ovine trophectoderm
    Biology of reproduction, 2018
    Co-Authors: Mohammed A. Elmetwally, Yasser Y. Lenis, Wanjin Tang, Fuller W Bazer
    Abstract:

    Ovine trophectoderm (oTr1) cells were used to investigate effects of epinephrine (EP), norepinephrine (NE), and dopamine (DA) on their proliferation, migration and adhesion, secretion of Interferon Tau (IFNT), and expression of genes for synthesis of polyamines and apoptosis. Expression of mRNAs for agmatinase (AGMAT), arginine decarboxylase (ADC), ornithine decarboxylase (ODC1), and solute carrier family 7 (SLC7A1) (cationic amino acid transporter, Y + system), member 1 increased (P 

  • chronicling the discovery of Interferon Tau
    Reproduction, 2017
    Co-Authors: Fuller W Bazer, W W Thatcher
    Abstract:

    It has been 38 years since a protein, now known as Interferon Tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. After 1979, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent the regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical Interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia. But, IFNT signaling through a STAT1/STAT2-independent pathway stimulates expression of genes, such as those for transport of glucose and amino acids, which are required for growth and development of the conceptus. Further, undefined mechanisms of action of IFNT are key to a servomechanism that allows ovine placental lactogen and placental growth hormone to affect the development of uterine glands and their expression of genes throughout gestation. IFNT also acts systemically to induce the expression of Interferon stimulated genes that influence secretion of progesterone by the corpus luteum. Finally, IFNT has great potential as a therapeutic agent due to its low cytotoxicity, anti-inflammatory properties and effects to mitigate diabetes, obesity-associated syndromes and various autoimmune diseases.

  • 1 Uterine Vein Infusion of Interferon Tau (IFNT) Extends Luteal Life Span in Ewes
    2016
    Co-Authors: Rebecca C. Bott, Thomas E Spencer, Fuller W Bazer, Ryan L. Ashley, Luiz E. Henkes, Alfredo Q. Antoniazzi, Jason E, Gordon D. Niswender, Natalia P. Smirnova, Russell V. Anthony
    Abstract:

    Running title: Endocrine actions of IFNT during early pregnancy Summary Sentence: Infusion of recombinant ovine Interferon Tau into the uterine vein regulates luteal gene expression and prolongs luteal lifespan in non-pregnant ewes

  • Published online before print 30 December 2009. DOI 10.1095/biolreprod.109.079467 Uterine Vein Infusion of Interferon Tau (IFNT) Extends Luteal Life Span in Ewes1
    2016
    Co-Authors: Rebecca C. Bott, Thomas E Spencer, Fuller W Bazer, Ryan L. Ashley, Luiz E. Henkes, Alfredo Q. Antoniazzi, Gordon D. Niswender, Natalia P. Smirnova, Jason E. Bruemmer, Russell V. Anthony
    Abstract:

    Interferon Tau (IFNT) from the ovine conceptus has paracrine actions on the endometrium that alter release of prostaglandin F2alpha (PGF) and protect the corpus luteum (CL). Antiviral activity in uterine vein blood and expression of Interferon-stimulated genes (ISGs) in CL is greater in pregnant than in nonpregnant ewes. We hypothesized that IFNT contributes to antiviral activity in uterine vein blood and has endocrine actions on the CL. Preadsorption of IFNT with antiserum against recombinant ovine (ro) IFNT revealed that antiviral activity in uterine vein blood from pregnant ewes was mediated by IFNT. Endocrine actions of IFNT were examined after infusing either roIFNT or bovine serum albumin (BSA; 200 lg/24 h; mini-osmotic pump) into the uterine vein of nonpregnant ewes from Day 10 to Day 11 postestrus. The abundance of ISG15 mRN

Thomas E Spencer - One of the best experts on this subject based on the ideXlab platform.

  • conceptus induced Interferon Tau dependent gene expression in bovine endometrial epithelial and stromal cells
    Biology of Reproduction, 2021
    Co-Authors: Heather L Chaney, Thomas E Spencer, P Lonergan, Gilles Charpigny, Susanta K Behura, Lindsay F Grose, Martin I Sheldon, James G Cronin, Daniel J Mathew
    Abstract:

    Bovine endometrium consists of epithelial and stromal cells that respond to conceptus Interferon Tau (IFNT), the maternal recognition of pregnancy (MRP) signal, by increasing expression of IFN-stimulated genes (ISGs). Endometrial epithelial and stromal cell specific ISGs are largely unknown but hypothesized to have essential functions during pregnancy establishment. Bovine endometrial epithelial cells were cultured in inserts above stromal fibroblast (SF) cells for 6 h in medium alone or with IFNT. The epithelial and SF transcriptomic response was analyzed separately using RNA sequencing and compared to a list of 369 DEGs recently identified in intact bovine endometrium in response to elongating bovine conceptuses and IFNT. Bovine endometrial epithelial and SF shared 223 and 70 DEGs in common with the list of 369 endometrial DEGs. Well known ISGs identified in the epithelial and SF were ISG15, MX1, MX2, and OAS2. DEGs identified in the epithelial but not SF included a number of IRF molecules (IRF1, IRF2, IRF3 and IRF8), mitochondria SLC transporters (SLC25A19, SLC25A28 and SLC25A30), and a ghrelin receptor (GHSR). Expression of ZC3HAV1, an anti-retroviral gene, increased specifically within the SF. Gene ontology analysis identified the type I IFN signaling pathway and activation of nuclear factor kappa B transcription factors as biological processes associated with the epithelial cell DEGs. This study has identified biologically relevant IFNT stimulated genes within specific endometrial cell types. The findings provide critical information regarding the effects of conceptus IFNT on specific endometrial compartments during early developmental processes in cattle.

  • Interferon Tau dependent and independent effects of the bovine conceptus on the endometrial transcriptome
    Biology of Reproduction, 2019
    Co-Authors: Thomas E Spencer, Gilles Charpigny, Daniel J Mathew, Jose Maria Sanchez, Claudia Passaro, Susanta K Behura, P Lonergan
    Abstract:

    This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of Interferon Tau (IFNT), conceptus origin (in vivo vs. in vitro), and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on day 7 of the estrous cycle. On day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498, and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. A total of 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes [melanophilin (MLPH), prominin-2 (PROM2), myeloid associated differentiation marker (MYADM), vomeronasal 1 receptor 4 like (VN1R4L) and 5-hydroxytryptamine receptor 1A (HTR1A)] were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene [ADP-ribosylation factor like GTPase 4C (ARL4C)] was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment.Summary SentenceElongating bovine conceptuses modify the adjacent endometrial transcriptome in a manner dependent and independent of Interferon Tau and related to conceptus origin and sex.

  • Interferon Tau-dependent and independent effects of the bovine conceptus on the endometrial transcriptome
    Biology of Reproduction, 2019
    Co-Authors: Daniel J Mathew, Thomas E Spencer, Gilles Charpigny, Jose Maria Sanchez, Claudia Passaro, Susanta K Behura, Patrick Lonergan
    Abstract:

    This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of Interferon Tau (IFNT), conceptus origin (in vivo vs. in vitro) and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on Day 7 of the estrous cycle. On Day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498 and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes (MLPH, PROM2, MYADM, VN1R4L, HTR1A) were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene (ARL4C) was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment

  • paracrine and endocrine actions of Interferon Tau ifnt
    Reproduction, 2017
    Co-Authors: Thomas R Hansen, L D P Sinedino, Thomas E Spencer
    Abstract:

    This review focuses on the paracrine and endocrine actions of Interferon Tau (IFNT) during pregnancy recognition and establishment in ruminants. Pregnancy recognition involves the suppression of the endometrial luteolytic mechanism by the conceptus to maintain progesterone production by the corpus luteum (CL). The paracrine antiluteolytic effects of conceptus-derived IFNT inhibit upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical IFN-stimulated genes (ISGs) and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy. Further, IFNT has endocrine effects on extrauterine cells and tissues. In sheep, IFNT induces luteal resistance to PGF2α, thereby ensuring survival of the CL for maintenance of pregnancy. The ISGs induced in circulating peripheral blood mononuclear cells by IFNT may also be useful as an indicator of pregnancy status in cattle. An increased knowledge of IFNT and ISGs is important to improve the reproductive efficiency in ruminants.

  • Interferon Tau (IFNT)
    Reference Module in Biomedical Sciences, 2017
    Co-Authors: R.m. Roberts, Thomas E Spencer
    Abstract:

    This article provides a short description of the discovery, mode of action, and characteristics of the Interferon Tau (IFNT), which is produced in abundance by the trophectoderm of peri-implantation conceptuses from the ruminant species for a restricted period during early pregnancy. These secreted molecules have an antiluteolytic action and help to ensure the continued production of progesterone by the ovary during early pregnancy. Conceivably, they also have other roles, including an ability to adjust the maternal endocrine and perhaps immune systems in the interests of conceptus survival. The emphasis in this article is on the antiluteolytic activity of the IFNT, how the IFNT is distinct from other type I IFNs, and how the IFNT might have evolved for a role in maternal recognition of pregnancy.

Kazuhiko Imakawa - One of the best experts on this subject based on the ideXlab platform.

  • thirty years of Interferon Tau research past present and future perspective
    Animal Science Journal, 2017
    Co-Authors: Kazuhiko Imakawa, Rulan Bai, Keigo Nakamura, Kazuya Kusama
    Abstract:

    The year 2017 marks the 30th year since the discovery was made of amino acid and complementary DNA sequences of ovine trophoblast protein-1 (oTP-1), later renamed as Interferon-Tau (IFNτ). Ovine TP-1 was originally found as a secretory product of sheep conceptuses that rescues maternal corpus luteum (CL) and in fact, the uterine infusion of oTP-1 extended inter-estrous intervals. Finding this signaling molecule as an IFN-like sequence was surprising to the scientific community in reproduction because a homologous molecule in humans possesses anti-viral and anti-prolific activity and is often used in human medicines. However, since its discovery was made, large efforts have been made in the elucidation of transcriptional regulation and functions of bovine and ovine IFNτs, more importantly, the improvement of pregnancy rates in sheep and cattle, most of which resulted in unsuccessful outcomes. In this review, physiological, cellular and molecular events associated with continued secretion of progesterone, maternal recognition of pregnancy, identification, transcriptional regulation and function of IFNτ, and its future perspectives will be discussed.

  • down regulation of Interferon Tau gene transcription with a transcription factor eomes
    Molecular Reproduction and Development, 2013
    Co-Authors: Toshihiro Sakurai, Rulan Bai, Hanako Bai, Atsushi Ideta, Yoshito Aoyagi, James D. Godkin, Daisuke Sato, Miki Arai, Kiyoshi Okuda, Kazuhiko Imakawa
    Abstract:

    Interferon Tau (IFNT), produced for a short interval during early pregnancy by the ruminant embryonic trophectoderm, is essential for the maintenance of early pregnancy, but the mechanism by which it is transcriptionally regulated has not been fully determined. To identify a transcription factor(s) involved in the down-regulation of IFNT genes, mRNAs for various known transcription factors were investigated by reverse-transcriptase and real-time PCR in conceptus tissues collected on Days 15, 17, and 21, or Days 17, 20, and 22 of ovine or bovine pregnancy, respectively. In particular, the T-box protein eomesodermin (EOMES) exhibited high mRNA expression in Day 17 or 22 ovine or bovine conceptuses. Interaction between EOMES and the identified transcription factors was studied using transient transfection, revealing that ovine/bovine IFNT-reporter transactivation was down-regulated by EOMES. Transcription factor interactions with EOMES were further studied through immunoprecipitation, demonstrating an association between EOMES and cAMP-response element binding protein (CREB)-binding protein (CREBBP). Uterine flushing media collected from cyclic or early pregnancy animals were added to bovine trophoblast CT-1 cells cultured on type-I collagen (monoculture) or bovine uterine epithelial cells (coculture) in an attempt to regulate EOMES expression. In the coculture, but not the monoculture, addition of uterine flushing from Day 17 pregnant animals resulted in increased EOMES expression in CT-1 cells. These results suggest that as conceptuses attach to the uterine epithelium, IFNT gene transcription is down-regulated by an increase in EOMES expression and EOMES–CREBBP binding in the attached trophoblast cells. Mol. Reprod. Dev. 80: 371–383, 2013. © 2013 Wiley Periodicals, Inc.

  • Down‐regulation of Interferon Tau gene transcription with a transcription factor, EOMES
    Molecular reproduction and development, 2013
    Co-Authors: Toshihiro Sakurai, Rulan Bai, Hanako Bai, Atsushi Ideta, Yoshito Aoyagi, James D. Godkin, Daisuke Sato, Miki Arai, Kiyoshi Okuda, Kazuhiko Imakawa
    Abstract:

    Interferon Tau (IFNT), produced for a short interval during early pregnancy by the ruminant embryonic trophectoderm, is essential for the maintenance of early pregnancy, but the mechanism by which it is transcriptionally regulated has not been fully determined. To identify a transcription factor(s) involved in the down-regulation of IFNT genes, mRNAs for various known transcription factors were investigated by reverse-transcriptase and real-time PCR in conceptus tissues collected on Days 15, 17, and 21, or Days 17, 20, and 22 of ovine or bovine pregnancy, respectively. In particular, the T-box protein eomesodermin (EOMES) exhibited high mRNA expression in Day 17 or 22 ovine or bovine conceptuses. Interaction between EOMES and the identified transcription factors was studied using transient transfection, revealing that ovine/bovine IFNT-reporter transactivation was down-regulated by EOMES. Transcription factor interactions with EOMES were further studied through immunoprecipitation, demonstrating an association between EOMES and cAMP-response element binding protein (CREB)-binding protein (CREBBP). Uterine flushing media collected from cyclic or early pregnancy animals were added to bovine trophoblast CT-1 cells cultured on type-I collagen (monoculture) or bovine uterine epithelial cells (coculture) in an attempt to regulate EOMES expression. In the coculture, but not the monoculture, addition of uterine flushing from Day 17 pregnant animals resulted in increased EOMES expression in CT-1 cells. These results suggest that as conceptuses attach to the uterine epithelium, IFNT gene transcription is down-regulated by an increase in EOMES expression and EOMES–CREBBP binding in the attached trophoblast cells. Mol. Reprod. Dev. 80: 371–383, 2013. © 2013 Wiley Periodicals, Inc.

  • Functions of Interferon Tau as an immunological regulator for establishment of pregnancy
    Reproductive Medicine and Biology, 2012
    Co-Authors: Hanako Bai, Toshihiro Sakurai, Hiroshi Fujiwara, Atsushi Ideta, Yoshito Aoyagi, James D. Godkin, Kazuhiko Imakawa
    Abstract:

    The establishment of a successful pregnancy requires a “fine quality embryo”, “maternal recognition of pregnancy”, and a “receptive uterus” during the period of conceptus implantation to the uterine endometrium. In ruminants, a conceptus cytokine, Interferon Tau (IFNT), a major cytokine produced by the peri-implantation trophectoderm, is known as a key factor for maternal recognition of pregnancy. IFNT can be considered one of the main factors in conceptus–uterus cross-talk, resulting in the rescue of ovarian corpus luteum (CL), induction of endometrial gene expressions, activation of residual immune cells, and recruitment of immune cells. Much research on IFNT has focused on the CL life-span (pregnancy recognition) and uterine gene expression through IFNT and related genes; however, immunological acceptance of the conceptus by the mother has not been well characterized. In this review, we will discuss the progress in IFNT and implantation research made by us and others for over 10 years, and relate this progress to pregnancy in mammalian species other than ruminants.

  • increase in dna methylation downregulates conceptus Interferon Tau gene expression
    Molecular Reproduction and Development, 2004
    Co-Authors: Hisashi Nojima, Kentaro Nagaoka, R K Christenson, Kunio Shiota, Kazuhiko Imakawa
    Abstract:

    Expression of ovine Interferon-Tau (oIFNt) genes, essential for the maternal recognition of pregnancy in ruminant ungulates, is restricted to the trophoblast and is not detected in any other cell types or tissues. Substantial secretion of oIFNt starts on day 12-13 of pregnancy (day 0 ¼day of estrus), reaches the highest on day 16-17, and then declines rapidly. Ovine IFNt mRNA, on the other hand, reaches the highest level on day 14 of pregnancy, 2-3 days before peak production of the protein. In this study, day 14 and 17 conceptuses treated with 5-aza-2 0 -deoxycyti- dine, an inhibitor of DNA methylation, were cultured in vitro and only day 17, not day 14, conceptuses resulted in upregulation of oIFNt gene expression. To gain insight into the molecular mechanism of oIFNt gene downregulation, the methylation status within 1 kb of the 5 0 -flanking region of oIFNt-o10 gene was investigated: CpG dinucleotides of this gene in day 14 ovine conceptuses were hypomethylated compared to day 20 conceptuses or other tissues. In vitro methyla- tion of oIFNt-o10-reporter constructs caused suppres- sion of reporter activity in transient transfections. Cotransfection of methyl-CpG-binding protein (MeCP2) with the reporter construct elicited further suppression of the reporter activity. In electrophoretic mobility shift assay (EMSA), patterns of shifted bands did not show much difference between methylated and unmethy- lated probes in distal regions, but exhibited differ- ences in the proximal region of upstream sequences of the oIFNt gene. These results provide evidence that changes in the degree of DNA methylation could be one of the major mechanisms leading to downregulation of the oIFNt-o10 gene during early gestation, and possibly its silencing in nonconceptus tissues. Mol. Reprod. Dev. 67: 396-405, 2004. 2004 Wiley-Liss, Inc.

Thomas R Hansen - One of the best experts on this subject based on the ideXlab platform.

  • paracrine and endocrine actions of Interferon Tau ifnt
    Reproduction, 2017
    Co-Authors: Thomas R Hansen, L D P Sinedino, Thomas E Spencer
    Abstract:

    This review focuses on the paracrine and endocrine actions of Interferon Tau (IFNT) during pregnancy recognition and establishment in ruminants. Pregnancy recognition involves the suppression of the endometrial luteolytic mechanism by the conceptus to maintain progesterone production by the corpus luteum (CL). The paracrine antiluteolytic effects of conceptus-derived IFNT inhibit upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical IFN-stimulated genes (ISGs) and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy. Further, IFNT has endocrine effects on extrauterine cells and tissues. In sheep, IFNT induces luteal resistance to PGF2α, thereby ensuring survival of the CL for maintenance of pregnancy. The ISGs induced in circulating peripheral blood mononuclear cells by IFNT may also be useful as an indicator of pregnancy status in cattle. An increased knowledge of IFNT and ISGs is important to improve the reproductive efficiency in ruminants.

  • Função do Interferon-Tau durante o reconhecimento materno da gestação em ruminantes
    Ciência Rural, 2011
    Co-Authors: Alfredo Q. Antoniazzi, L K Henkes, João Francisco Coelho De Oliveira, Thomas R Hansen
    Abstract:

    Maternal recognition of pregnancy is the period when the conceptus signals its presence to the dam. In ruminants, it requires conceptus elongation, which coincides with maximum production of Interferon-Tau (IFNT). Conceptus IFNT acts in a paracrine manner silencing estrogen receptor alpha (ESR1) and oxytocin receptor (OXTR) in the luminal epithelium, thus preventing luteolytic prostaglandin F2 alpha (PGF2 ) pulses. Besides its role during maternal recognition of pregnancy, IFNT induces the expression of several Interferon stimulated genes (ISGs) in the endometrium, corpus luteum (CL) and blood cells. Recently, it was suggested an endocrine role for IFNT during the period of maternal recognition of pregnancy in sheep. It was demonstrated that infusion of IFNT into the uterine vein can extend the estrous cycle beyond 32 days. This direct action of IFNT in extrauterine tissues induces ISGs expression, which might be involved in the rescue of the CL from the luteolytic effects of PGF2 pulses.

  • endocrine actions of Interferon Tau in ruminants
    Reproduction in domestic ruminants VII. Proceedings of the Eighth International Symposium on Reproduction in Domestic Ruminants Anchorage Alaska Septe, 2010
    Co-Authors: Thomas R Hansen, Rebecca C. Bott, Ryan L. Ashley, Alfredo Q. Antoniazzi, L K Henkes, H Han
    Abstract:

    The ovine conceptus releases Interferon-Tau (IFNT), which prevents upregulation of the endometrial estrogen receptor (ESR1) and, consequently, oxytocin receptor (OXTR), thereby disrupting pulsatile release of prostaglandin F2alpha (PGF) in response to oxytocin. IFNT, through paracrine action on the endometrium, protects the corpus luteum (CL) during maternal recognition of pregnancy. Pregnancy also induces IFN stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs), which is interpreted to reflect a "prompted" antiviral and immune cell response peripherally in ruminants. IFNT was recently demonstrated to be released from the uterus in amounts of 200 microg (2 x 10(7) U)/24 h via the uterine vein and to induce ISGs in the CL during maternal recognition of pregnancy. Delivery of recombinant ovine (ro) IFNT into the uterine vein in a location that is upstream of the utero-ovarian plexus from Day 10 to 17 maintained serum progesterone concentrations and extended normal 16-17 d estrous cycles to beyond 32 d. It is concluded from these studies that IFNT is released into the uterine vein and initiates a peripheral antiviral response to protect pregnancy from maternal viral infection. It also may have endocrine action through inducing luteal resistance to PGF and longer-term survival of the CL and maintenance of pregnancy.

  • complex induction of bovine uterine proteins by Interferon Tau
    Biology of Reproduction, 1998
    Co-Authors: Kimberly L Staggs, K J Austin, Gregory Johnson, Glaucia M Teixeira, Cody T Talbott, Vern A Dooley, Thomas R Hansen
    Abstract:

    Interferon-Tau (IFN-Tau) is released by the conceptus and induces two uterine proteins during early pregnancy: ubiquitin cross-reactive protein (UCRP) and granulocyte chemotactic protein-2 (GCP-2). The present experiments were designed to determine whether detection (Western blot) of cytosolic UCRP and release of GCP-2 could be used to examine IFN-Tau signal transduction in cultured endometrial explants and primary epithelial cells. Recombinant (r) type 1 IFNs (rboIFN-Tau and rboIFN-alpha; 5, 25, 100 nM) induced UCRP, but only rboIFN-Tau induced GCP-2 in explant culture. Recombinant boIFN-Tau and conceptus secretory proteins containing native IFN-Tau induced UCRP and GCP-2 in cultured primary epithelial cells. All concentrations of rboIFN-alpha (25, 50, 100 nM) induced UCRP, but only the highest concentration induced GCP-2 in cultured primary epithelial cells. Interestingly, phorbol ester (100, 500, 1000 ng/ml) induced GCP-2, but it had no effect on UCRP. Because type 1 IFNs induce UCRP, IFN-Tau probably interacts with the janus kinase (Jak)-associated IFN-alpha receptor to phosphorylate signal transducers and activators of transcription (STAT) and/or Interferon regulatory factor-1 (IRF-1). However, IFN-Tau-specific induction of GCP-2 may involve a variant type 1 receptor subunit or activators of transcription that are associated with protein kinase C and the Jak/STAT/IRF-1 pathway.

  • pregnancy and Interferon Tau induce conjugation of bovine ubiquitin cross reactive protein to cytosolic uterine proteins
    Biology of Reproduction, 1998
    Co-Authors: Gregory Johnson, K J Austin, E A Van Kirk, Thomas R Hansen
    Abstract:

    Conceptus-derived Interferon-Tau (IFN-Tau) induces bovine endometrial ubiquitin cross-reactive protein (UCRP) mRNA and protein on Days 15-21 of pregnancy. Bovine UCRP retains the Leu-Arg-Gly-Gly C-terminal sequence of ubiquitin that ligates to and directs degradation of cytosolic proteins. The objectives of the present experiments were to determine whether UCRP became conjugated to endometrial cytosolic proteins during early pregnancy and in response to recombinant bovine (rbo) IFN-Tau. Ubiquitin (8 kDa), UCRP (17 kDa), and conjugates thereof (> or = 30 kDa) were quantitated using Western blotting and densitometry. Endometrial ubiquitin and its conjugates did not differ between Day 18 pregnant and nonpregnant cows, or between control and rboIFN-Tau-treated (25 nM) explant cultures (Day 14; nonpregnant). Bovine UCRP was induced in endometrium from pregnant as compared with nonpregnant cows. Conjugation of endometrial proteins to UCRP was induced in pregnant as compared to nonpregnant cows. Recombinant boIFN-Tau induced UCRP and its conjugates in cultured endometrial explants from nonpregnant cows. It is concluded that UCRP, in response to rboIFN-Tau, becomes conjugated to endometrial cytosolic proteins during early pregnancy. The regulation of uterine proteins by UCRP may be integral to the maintenance of early pregnancy in ruminants.

Daniel J Mathew - One of the best experts on this subject based on the ideXlab platform.

  • conceptus induced Interferon Tau dependent gene expression in bovine endometrial epithelial and stromal cells
    Biology of Reproduction, 2021
    Co-Authors: Heather L Chaney, Thomas E Spencer, P Lonergan, Gilles Charpigny, Susanta K Behura, Lindsay F Grose, Martin I Sheldon, James G Cronin, Daniel J Mathew
    Abstract:

    Bovine endometrium consists of epithelial and stromal cells that respond to conceptus Interferon Tau (IFNT), the maternal recognition of pregnancy (MRP) signal, by increasing expression of IFN-stimulated genes (ISGs). Endometrial epithelial and stromal cell specific ISGs are largely unknown but hypothesized to have essential functions during pregnancy establishment. Bovine endometrial epithelial cells were cultured in inserts above stromal fibroblast (SF) cells for 6 h in medium alone or with IFNT. The epithelial and SF transcriptomic response was analyzed separately using RNA sequencing and compared to a list of 369 DEGs recently identified in intact bovine endometrium in response to elongating bovine conceptuses and IFNT. Bovine endometrial epithelial and SF shared 223 and 70 DEGs in common with the list of 369 endometrial DEGs. Well known ISGs identified in the epithelial and SF were ISG15, MX1, MX2, and OAS2. DEGs identified in the epithelial but not SF included a number of IRF molecules (IRF1, IRF2, IRF3 and IRF8), mitochondria SLC transporters (SLC25A19, SLC25A28 and SLC25A30), and a ghrelin receptor (GHSR). Expression of ZC3HAV1, an anti-retroviral gene, increased specifically within the SF. Gene ontology analysis identified the type I IFN signaling pathway and activation of nuclear factor kappa B transcription factors as biological processes associated with the epithelial cell DEGs. This study has identified biologically relevant IFNT stimulated genes within specific endometrial cell types. The findings provide critical information regarding the effects of conceptus IFNT on specific endometrial compartments during early developmental processes in cattle.

  • Interferon Tau dependent and independent effects of the bovine conceptus on the endometrial transcriptome
    Biology of Reproduction, 2019
    Co-Authors: Thomas E Spencer, Gilles Charpigny, Daniel J Mathew, Jose Maria Sanchez, Claudia Passaro, Susanta K Behura, P Lonergan
    Abstract:

    This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of Interferon Tau (IFNT), conceptus origin (in vivo vs. in vitro), and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on day 7 of the estrous cycle. On day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498, and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. A total of 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes [melanophilin (MLPH), prominin-2 (PROM2), myeloid associated differentiation marker (MYADM), vomeronasal 1 receptor 4 like (VN1R4L) and 5-hydroxytryptamine receptor 1A (HTR1A)] were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene [ADP-ribosylation factor like GTPase 4C (ARL4C)] was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment.Summary SentenceElongating bovine conceptuses modify the adjacent endometrial transcriptome in a manner dependent and independent of Interferon Tau and related to conceptus origin and sex.

  • Interferon Tau-dependent and independent effects of the bovine conceptus on the endometrial transcriptome
    Biology of Reproduction, 2019
    Co-Authors: Daniel J Mathew, Thomas E Spencer, Gilles Charpigny, Jose Maria Sanchez, Claudia Passaro, Susanta K Behura, Patrick Lonergan
    Abstract:

    This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of Interferon Tau (IFNT), conceptus origin (in vivo vs. in vitro) and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on Day 7 of the estrous cycle. On Day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498 and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes (MLPH, PROM2, MYADM, VN1R4L, HTR1A) were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene (ARL4C) was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment