| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Immunology |
Center for Animal Biotechnology and Genomics, Department of Animal Science3
Department of Veterinary Anatomy and Public Health,4 Texas A&M University, College Station, Texas 77843
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
chain and ß2-microglobulin (ß2MG), play an important role in immune rejection responses by discriminating self and nonself and are increased by type I interferons during antiviral responses. Interferon tau (IFN
), the pregnancy-recognition signal in ruminants, is a type I interferon produced by the ovine conceptus between Days 11 and 21 of gestation. In study 1, expression of MHC class I chain and ß2MG mRNA and protein was detected primarily in endometrial luminal epithelium (LE) and glandular epithelium (GE) on Days 10 and 12 of the estrous cycle and pregnancy. On Days 14–20 of pregnancy, MHC class I and ß2MG expression increased only in endometrial stroma and GE and, concurrently, was absent in LE and superficial ductal GE (sGE). Although neither MHC class I nor ß2MG proteins were detected in Day 20 trophectoderm, ß2MG mRNA was detected in conceptus trophectoderm. In study 2, cyclic ewes were ovariectomized on Day 5, treated daily with progesterone to Day 16, received intrauterine infusions between Days 11 and 16 of either control serum proteins or recombinant ovine IFN, and were hysterectomized on Day 17. The IFN increased MHC class I and ß2MG expression only in endometrial stroma and GE. During pregnancy, MHC class I and ß2MG gene expression is inhibited in endometrial LE and sGE but, paradoxically, is stimulated by IFN in the stroma and GE. The silencing of MHC class I chain and ß2MG genes in the endometrial LE and sGE during pregnancy recognition and establishment may be a critical mechanism preventing immune rejection of the conceptus allograft.
ß2-microglobulin, interferon, major histocompatibility complex, ovine, uterus
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
chain associated noncovalently with a light ß chain, termed ß2-microglobulin (ß2MG), that are expressed on the cell membranes of most somatic cells. The MHC class I molecules play an important role in discrimination of self versus nonself by presenting foreign antigenic peptides to cytotoxic T lymphocytes. The cytotoxic T lymphocytes recognize foreign protein antigens in association with MHC class I molecules and then kill foreign or infected cells. This mechanism is a key component of host defense as well as immune histocompatibility of transplanted tissue.
Expression of MHC class I molecules is regulated during development and differentiation [8–11] and is controlled by various mitogens and cytokines, including type I interferons (IFNs) [12]. The IFNs enhance cellular immune responses by regulating immunomodulatory systems, including increasing levels of MHC class I and class II antigens. Although both type I and type II IFNs induce the expression of MHC class I molecules [12, 13], MHC class II is only induced by IFN
, a type II IFN [14]. In the absence of signal transducer and activator of transcription (Stat) 1 and Stat2, IFN induction of the MHC complex is abrogated [15, 16]. The Stat1 plays a critical role in maintaining basal expression of MHC class I antigens [17]. In addition, IFN regulatory factor (IRF)-1, a Stat1-regulated gene, is critical for tissue-specific modulation of MHC class I molecules in kidney cells [18], antigen-presenting cells [19], and astrocytes [20].
In sheep, the mononuclear cells of the conceptus trophectoderm synthesize and secrete IFN, a novel member of the type I IFN family, between Days 11 and 21 of gestation [21]. The IFN is the pregnancy-recognition signal in ruminants. All type I IFNs, including IFN, exert their action through a common receptor, which consists of two subunits, IFNAR1 and IFNAR2c. In the ovine uterus, both IFNAR1 and IFNAR2 are expressed in the endometrial luminal epithelium (LE), superficial ductal glandular epithelium (sGE), and stroma [22]. The IFN induces or increases expression of many IFN-stimulated genes (ISGs) in a cell-type specific manner in the uterine endometrium. These ISGs include ß2MG [23], Stat1 and Stat2 [24–28], IRF-1 [24, 25, 27, 28], ISG17 [25, 29–31], Mx protein [32, 33], and 2',5'-oligoadenylate synthetase (OAS) [34, 35]. The IFN regulates gene transcription through an intracellular signal transduction system involving Stats and IRFs [25–28]. During pregnancy recognition and establishment, ISGs, including Stat1, Stat2, IRF-9, ISG17, and OAS, are induced or increased only in the endometrial stroma and middle-to-deep GE, because expression of these genes is not detected in the endometrial LE and sGE [28–31, 35]. A known transcriptional repressor of ISGs as well as of type I IFNs [36–38], IRF-2 is constitutively expressed in endometrial LE and sGE [28]. Available evidence supports the hypothesis that IRF-2 expression in the endometrial LE and sGE prevents IFN induction of ISGs in those epithelia because of the lack of critical intracellular signal transduction molecules [28].
To our knowledge, the effects of pregnancy and IFN on cell type-specific expression of MHC class I and ß2MG genes in the ovine uterus have not been reported. Our working hypothesis is that IFN from the ovine conceptus will only induce or increase expression of MHC class I and ß2MG genes in the endometrial stroma and GE. To test this hypothesis, studies were conducted to determine effects of the estrous cycle, pregnancy, and intrauterine administration of recombinant ovine IFN on expression of MHC class I chain and ß2MG genes in the ovine uterine endometrium.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Mature ewes of primarily Suffolk breeding were observed daily for estrus using vasectomized rams. All ewes exhibited at least two estrous cycles of normal duration (
16–18 days). Experimental and surgical procedures were approved by the University Laboratory Animal Care and Use Committee of Texas A&M University.
In study 1, ewes were mated at estrus (Day 0) to an intact or vasectomized ram. Ewes were then hysterectomized (n = 5 ewes/day) on Day 10, 12, 14, or 16 of the estrous cycle or Day 10, 12, 14, 16, 18, or 20 of pregnancy. Pregnancy was confirmed on Days 10–16 postmating by the presence of one or more apparently normal conceptuses in uterine flushings.
In study 2, 10 cyclic ewes were ovariectomized and fitted with intrauterine catheters on Day 5 postestrus as described previously [30, 31]. Ewes (n = 5 ewes/treatment) received i.m. injections of 50 mg of progesterone daily from Days 5 to 16 and intrauterine infusions of either 200 µg of control serum proteins (CX; ovine serum proteins) or recombinant ovine IFN (roIFN; 2 x 107 antiviral units) [39] from Days 11 to 16. Proteins were prepared for intrauterine injection as described previously [30, 31]. All ewes were hysterectomized on Day 17.
For both studies, portions (1 cm) from the middle region of the uterine horn were fixed at hysterectomy in fresh 4% paraformaldehyde in PBS (pH 7.2) for 24 h, washed in 70% (v/v) ethanol for 24 h, and then embedded in Paraplast-Plus (Oxford Labware, St. Louis, MO) for in situ hybridization analyses. Several portions (0.5 cm) from the midregion of the uterine horn were also embedded in Tissue-Tek Optimal Cutting Temperature (OCT) compound (Miles, Inc., Oneonta, NY), frozen in liquid nitrogen, and then stored at -80°C for immunofluorescence analyses. The remaining endometrial tissue was physically dissected from myometrium, frozen in liquid nitrogen, and then stored at -80°C for RNA extraction and slot-blot hybridization analyses.
Cloning of MHC Class I Molecules
Partial cDNAs for ovine MHC class I and ß2MG mRNAs were amplified by reverse transcription-polymerase chain reaction (PCR) of total RNA from Day 15 pregnant ovine endometrium using primers based on the ovine MHC class I cDNA (GenBank accession no. M34676; forward, 5'-GAC GGC AGA GAT TAC ATC G-3'; reverse, 5'-CAT TGA GGA AGT GAG GAA GG-3') or human ß2MG cDNA (GenBank accession no. NM_004048; forward, 5'-ATT CAG GTA TAC TCA CG-3'; reverse, 5'-TGG GGG TGA ATT CAG TGT-3'). The PCR amplification was conducted as follows for MHC class I and ß2MG using PCR Optimized Buffer (Invitrogen, Carlsbad, CA): 95°C for 2 min; 30 sec at 95°C, 1 min at 42°C, and 1 min at 72°C for 4 cycles; 30 sec at 95°C, 1 min at 53°C, and 30 sec at 72°C for 35 cycles; and 72°C for 10 min. The amplified MHC class I (504-base pairs [bp]) and ß2MG (198-bp) PCR products were subcloned into pCRII vector using a T/A Cloning Kit (Invitrogen). The partial cDNAs were sequenced in both directions using an ABI PRISM Dye Terminator Cycle Sequencing Kit and ABI PRISM automated DNA sequencer (Perkin-Elmer Applied Biosystems, Foster City, CA) to confirm identity.
RNA Isolation and Analyses
RNA Isolation Total cellular RNA was isolated from frozen endometrial tissue using Trizol reagent (Gibco-BRL, Bethesda, MD). The quantity was assessed spectrophotometrically.
Slot-blot hybridization analysis
Steady-state levels of MHC class I and ß2MG mRNAs were assessed by slot-blot hybridization using methods described previously [28, 31]. Radiolabeled antisense cRNA probes were generated from linearized ovine MHC class I and ß2MG cDNAs by in vitro transcription with [-32P]UTP. Denatured total endometrial RNA (20 µg) from each ewe was hybridized with radiolabeled cRNA probes. To correct for variation in total RNA loading, a duplicate RNA slot membrane was hybridized with a radiolabeled antisense 18 rRNA cRNA (pT718S; Ambion, Austin, TX). After washing, the blots were digested with ribonuclease A. The radioactivity associated with each slot was quantified using a Typhoon 8600 MultiImager (Molecular Dynamics, Piscataway, NJ) and is expressed as total counts (TC).
In Situ Hybridization Analysis
The MHC class I and ß2MG mRNAs were localized in uterine tissue sections (thickness, 5 µm) by in situ hybridization analysis using methods described previously [28, 31]. Deparaffinized, rehydrated, and deproteinated uterine tissue sections were hybridized with radiolabeled antisense or sense cRNA probes generated from linearized ovine MHC class I and ß2MG cDNAs by in vitro transcription with [-35S]UTP. After hybridization, washing, and ribonuclease A digestion, slides were dipped in NTB-2 liquid photographic emulsion (Kodak, Rochester, NY), stored at 4°C for 1 wk, and developed in Kodak D-19 developer. Slides were then counterstained with Harris modified hematoxylin (Fisher Scientific, Fairlawn, NJ), dehydrated through a graded series of alcohol to xylene, and protected with a coverslip. Images of representative fields were recorded using a Nikon Eclipse 1000 photomicroscope (Nikon Instruments, Inc., Lewisville, TX) fitted with a Nikon DXM1200 digital camera.
Immunofluorescence Analyses
Frozen sections (thickness, 4–8 µm) of uterine tissues embedded in OCT compound were cut with a cryostat and mounted on Superfrost/Plus microscope slides (Fisher Scientific, Pittsburgh, PA). Using methods described previously [28, 35], sections were fixed in -20°C methanol, permeabilized with 0.3% Tween-20 in 0.02 M PBS, blocked in antibody dilution buffer (two parts 0.02 M PBS, 1.0% BSA, and 0.3% Tween-20 [pH 8.0] and one part glycerol) containing 10% normal goat serum, and incubated overnight at 4°C with primary antibodies. Antibodies were mouse anti-ovine MHC class I (PT85A) at 10 µg/ml from VMRD, Inc. (Pullman, WA); rabbit anti-human ß2MG (RDI-CBL307) at 10 µg/ml from Research Diagnostics, Inc. (Flanders, NJ); and normal rabbit immunoglobulin (Ig) G (no. I5006) and normal mouse IgG (no. I5381) from Sigma-Aldrich (St. Louis, MO). Immunoreactive protein was detected using a fluorescein-conjugated goat anti-rabbit IgG or goat anti-mouse IgG from Zymed (San Francisco, CA). Sections were then rinsed and overlaid with a coverslip and Prolong Antifade mounting reagent (Molecular Probes, Eugene, OR). Images of representative fields were recorded using a Zeiss Axioplan2 microscope (Carl Zeiss, Thornwood, NY) fitted with a Hamamatsu C-5810 chilled three-color CCD camera (Hamamatsu Corporation, Bridgewater, NJ).
Statistical Analyses
Data from slot-blot hybridization analyses were subjected to least-squares ANOVA (LS-ANOVA) using the general linear models procedures of the Statistical Analysis System [40]. Slot-blot hybridization data for MHC class I and ß2MG mRNAs were corrected for differences in sample loading using the 18S rRNA data as a covariate in LS-ANOVA. Data from study 1 were analyzed for effects of day, pregnancy status (cyclic or pregnant), and their interaction. Within pregnancy status, least-squares regression analyses were used to determine effects of day on endometrial mRNA levels. Data from study 2 were subjected to one-way LS-ANOVA. All tests of significance were performed using the appropriate error terms according to the expectation of the mean squares for error. A P value of 0.05 or less was considered to be significant. Data are presented as the least-square mean with SEM.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Steady-state levels of MHC class I and ß2MG mRNA in endometrium from cyclic and pregnant ewes were determined by slot-blot hybridization analysis (Fig. 1). The MHC class I and ß2MG mRNAs were not affected (P > 0.10) by day of the estrous cycle. In endometrium from pregnant ewes, MHC class I and ß2MG mRNAs were lowest on Days 10 and 12, increased between Days 12 and 14, and remained high thereafter (P < 0.01, quadratic). Expression of MHC class I and ß2MG mRNAs in the endometrium on Days 14 or 16 of pregnancy was approximately 3-fold greater than on Days 14 or 16 of the estrous cycle (day x pregnancy status, P < 0.001).
|
Spatial changes in endometrial expression of MHC class I and ß2MG mRNAs in uteri of cyclic and pregnant ewes were determined by in situ hybridization analysis (Figs. 2–4). In cyclic ewes, expression of MHC class I mRNA (Fig. 2) and ß2MG mRNA (Fig. 3) was detected in the LE, GE, and stroma of the ovine endometrium, with the most abundant expression in the LE and sGE on Days 10 and 12. In pregnant ewes, MHC class I and ß2MG mRNAs were detected in endometrial LE only on Days 10 and 12. Interestingly, expression of these mRNAs was absent in LE or sGE but increased in the stroma and middle-to-deep GE between Days 14 and 20. As shown in Figure 4, MHC class I mRNA was not detected in conceptus trophectoderm, but ß2MG mRNA was detected in conceptus trophectoderm on Day 20.
|
|
|
Immunofluorescence Localization of MHC Class I and ß2MG Protein in Ovine Endometrium (Study 1)
Localization of MHC class I and ß2MG proteins using immunofluorescence analyses indicated that immunoreactive MHC class I (Fig. 5A) and ß2MG (Fig. 5B) proteins were present in endometrial LE from pregnant ewes only on Days 10 and 12 and not between Days 14 and 20. In contrast, expression of MHC class I and ß2MG proteins increased in the stroma and GE between Days 14 and 20 of pregnancy. Neither MHC class I nor ß2MG proteins were detected in the conceptus trophectoderm.
|
Intrauterine Administration of roIFN Increases Expression of MHC Class I and ß2MG in Ovine Endometrium (Study 2)
Intrauterine infusion of roIFN into progesterone-treated ewes elicited a 3.8-fold increase (P < 0.0001) in steady-state levels of MHC class I mRNA (control proteins vs. roIFN: 10 936 vs. 41 167 ± 2096 TC) and a 2.7-fold increase (P < 0.0001) in ß2MG mRNA (control proteins vs. roIFN: 3114 vs. 8452 ± 210 TC) in the endometrium.
In situ hybridization analyses revealed that roIFN increased MHC class I and ß2MG mRNA expression specifically in the endometrial stroma and middle-to-deep GE but not in the LE or sGE (Fig. 6, A and B). Similarly, immunoreactive MHC class I (Fig. 6C) and ß2MG (Fig. 6D) proteins were detected only in the stroma of CX ewes. Intrauterine infusion of roIFN increased expression of both proteins in the stroma and middle-to-deep GE but not in the LE or sGE.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
. The partial ovine MHC class I chain cDNA used for in situ hybridization should detect multiple transcripts from all ovine MHC class I genes based on sequence homology searches of GenBank. Results of the present study clearly illustrate that MHC class I and ß2MG genes in the ovine endometrium increase in response to pregnancy and conceptus-derived IFN but only in the endometrial stroma and middle-to-deep GE. Paradoxically, these genes were absent in the uterine LE and sGE of pregnant and IFN-infused cyclic ewes. The absence of MHC class I chain and ß2MG genes in the LE is hypothesized to be advantageous, because the LE directly interfaces with conceptus trophectoderm during synepitheliochorial placentation. Placentation in ruminants involves the formation of multinucleated syncytium between binucleate cells of the conceptus trophectoderm and the endometrial LE of the maternal uterus [21]. Therefore, these multinucleate cells could express fetal "foreign" antigens on their surface to the maternal immune system. However, the combined lack of MHC class I chain and ß2MG proteins in the endometrial LE and sGE and conceptus trophectoderm effectively precludes expression of foreign fetal antigens on the syncytial cells.
In the present study, in situ hybridization and immunofluorescence analyses revealed that both MHC class I and ß2MG mRNA and proteins are expressed in LE, GE, and stroma of cyclic and early pregnant ewes on Days 10 and 12. However, expression of these genes was undetectable in LE and sGE of the ovine uterus after Day 14 of pregnancy but was increased in stroma and GE. This pattern of expression is similar to that of other ISGs, including Stat1, Stat2, IRF-9, IRF-1, ISG17, and OAS [28, 29, 36]. The expression of all these ISGs is induced or increased only in the endometrial stroma and GE while being simultaneously repressed or silenced in the LE and sGE in response to pregnancy or IFN. The IFN induces or increases levels of MHC class I expression in vitro in ovine endometrial cells [41] and in murine cerebrovascular endothelial cells [42] and increases levels of ß2MG secreted by endometrial explants from Day 12 cyclic ewes [23]. In the present study, intrauterine infusion of IFN into the uterus of cyclic ewes in vivo increased MHC class I and ß2MG expression only in endometrial stroma and GE.
The absence of ISGs, including MHC class I and ß2MG, in the LE and sGE has been attributed to IRF-2, a potent transcriptional repressor in the IFN signaling system [28]. In the ovine uterus, IRF-2 is expressed only in the LE and sGE in the endometrium of cyclic and pregnant ewes and increases during early pregnancy [28]. The IRF-2 binds to IFN consensus sequences (ICS), IFN-stimulated response elements (ISRE), and IRF elements and represses their basal and stimulated transcriptional activity [28, 43]. The promoter/enhancer regions of MHC class I and ß2MG genes contain conserved cis-acting elements that include enhancer A and ICS [44–46]. Enhancer A is recognized by nuclear factor kappa B (NF
B), whereas ICS contains an ISRE that binds IRFs and IFN-stimulated gene factor (ISGF) 3 transcription factors. The NFB and IRF-1 transcription factors interact with each other to synergistically increase MHC class I gene transcription, whereas IRF-2 inhibits NFB induction of MHC class I and ß2MG in CHP-126 neuroblastoma cells [45, 47]. Available evidence supports the hypothesis that the increase in epithelial IRF-2 during early pregnancy in the endometrium represses or silences transcription of the MHC class I chain and ß2MG genes.
Furthermore, the absence of Stat1, Stat2, and IRF-9 in the endometrial LE during early pregnancy prevents IFN induction of these genes in the endometrial LE and sGE, because the ISGF3 (Stat1, Stat2, and IRF-9 heterotrimer) and IRF-1 transcription factors cannot be formed in response to IFN. The IRF-1 gene is dependent on transactivation by gamma-activated factor, a homodimer of Stat1.
In ovine endometrial cells and human cell lines, ovine IFN activates the classical type I IFN signaling pathway, including phosphorylation of Stat1 and Stat2 that lead to formation of ISGF3 and IRF-1 transcription factor complexes [25–27]. In the absence of Stat1 and Stat2, induction of the MHC complex by type I IFNs is abrogated [15, 16]. The Stat1 also plays a role to maintain basal expression of the MHC class I antigens [17]. The IRF-1 null fibroblasts express MHC class I in response to IFN [48], suggesting that Stat1 and ISGF3 are sufficient for induction of MHC class I gene. Although ISGF3 and IRF-1 are not detectable in LE and sGE of the pregnant ovine uterus, they are expressed in the endometrial stroma and middle-to-deep GE during early pregnancy [28]. Thus, IFN induction of or increase in ISGs, including MHC class I and ß2MG, is restricted to the endometrial stroma and GE, because they possess a complete repertoire of Stat1, Stat2, IRF-9, and IRF-1 signaling molecules.
In the present study, expression of MHC class I chain and ß2MG genes were detected in the endometrial LE and sGE on Days 10 and 12 of the estrous cycle and early pregnancy. However, expression was not detected thereafter or in progesterone-treated Day 17 cyclic ewes infused with control proteins from Days 11 to 16 from study 2. The expression of several other ISGs, including ISG17, OAS, and IRF-1, has been observed at low levels in the endometrial LE and sGE [28, 29, 33, 35]. A possible explanation is that positive- and negative-acting transcription factors simultaneously regulate expression of these genes. Even though the IRF-2 repressor is expressed in the LE and sGE constitutively in the ovine uterus, transactivators likely are present that enhance expression of many ISGs through elements that are not influenced by IRF-2. Indeed, many of the promoter regions of genes stimulated by type I IFNs contain predicted progesterone receptor (PR) elements, including human ß2MG and bovine ISG17, as determined by bioinformatics software (unpublished results). Indeed, the pattern of expression of many ISGs in the ovine uterus parallels the presence of the PR between Days 5 and 11 and then loss of the PR after Days 11–12 [49]. Recent evidence indicates that the bovine ISG17 promoter is responsive to liganded PR (unpublished results). Therefore, the lack of MHC class I chain and ß2MG gene expression in the endometrial LE and sGE after Day 12 of the estrous cycle and pregnancy may result from the absence of the PR. This hypothesis will be tested in future experiments using a number of ISG promoters.
Expression of MHC class I and ß2MG genes is regulated during development and differentiation of cells and tissues [8–11]. In mice, MHC class I was undetectable in placenta, whereas ß2MG was expressed in the developing placenta that originates from extraembryonic derivatives of the early stage embryo [9]. Results of the present study were similar in that expression of ß2MG mRNA, but not MHC class I mRNA, was detected in conceptus trophectoderm. Interestingly, ß2MG protein was not detected in conceptus trophectoderm. The discrepancy between mRNA and protein expression patterns may simply result from specific posttranslational modifications of the ovine endometrial ß2MG protein that prevent detection with the anti-human ß2MG IgG. It is also possible that translation of the ß2MG mRNA may be blocked in the trophectoderm by an unknown mechanism involved in proliferation and growth of the conceptus. Alternatively, ß2MG may be immediately secreted after synthesis so that it is not detectable in either trophectoderm or LE because of the absence of MHC class I chain expression. The ß2MG does not directly attach to the cell membrane in vivo; rather, it is noncovalently associated with the chain of MHC class I to stabilize its tertiary structure on the nucleated cell surface [50]. In the absence of membrane-anchored MHC class I molecules, ß2MG is shed from cell surfaces into body fluids and then catabolized in the kidney [51]. Release of ß2MG is increased under abnormal physiological and pathological conditions [51–54]. The function of free ß2MG remains unclear; however, Min et al. [55] found that ß2MG suppressed proliferation of primary myeloma cells in vitro. Furthermore, ß2MG is an essential component of the IgG transporter, FcRn, expressed in the human placental syncytiotrophoblast [56] and also protects IgG from catabolism [57]. Thus, ß2MG may play multiple roles in regulating stromal, GE, and immune cell functions related to Igs that influence the conceptus in the pregnant ovine uterus.
In conclusion, results of the present study are the first, to our knowledge, to indicate that pregnancy and IFN increase expression of MHC class I molecules in endometrial stroma and GE but not in the LE, sGE, and trophectoderm during implantation. The silencing mechanism (or mechanisms) for expression of MHC class I molecules by the LE and trophectoderm in the ovine uterus remains to be established. However, the absence of MHC class I molecules in LE, sGE, and trophectoderm during implantation may be critical for protection of the conceptus allograft from immune rejection, because conceptus trophectoderm is in direct contact with LE, sGE, and immune cells of the uterus as it undergoes proliferation and growth during the peri-implantation period.
|
FOOTNOTES |
|---|
2 Correspondence: Fuller W. Bazer, Center for Animal Biotechnology and Genomics, 442D Kleberg Center, 2471 TAMU, Texas A&M University, College Station, TX 77843-2471. FAX: 979 845 9938; fbazer{at}cvm.tamu.edu
Received: 24 October 2002.
First decision: 18 November 2002.
Accepted: 2 December 2002.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
promoter and functional regulation by ovine interferon tau. Endocrinology 2001 142:2879-2887This article has been cited by other articles:
|
|
 |
|
  M. M. Joyce, J. R. Burghardt, R. C. Burghardt, R. N. Hooper, F. W. Bazer, and G. A. Johnson Uterine MHC Class I Molecules and {beta}2-Microglobulin Are Regulated by Progesterone and Conceptus Interferons during Pig Pregnancy J. Immunol., August 15, 2008; 181(4): 2494 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Oliveira, L. E. Henkes, R. L. Ashley, S. H. Purcell, N. P. Smirnova, D. N. R. Veeramachaneni, R. V. Anthony, and T. R. Hansen Expression of Interferon (IFN)-Stimulated Genes in Extrauterine Tissues during Early Pregnancy in Sheep Is the Consequence of Endocrine IFN-{tau} Release from the Uterine Vein Endocrinology, March 1, 2008; 149(3): 1252 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E Spencer, O. Sandra, and E. Wolf Genes involved in conceptus-endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches Reproduction, February 1, 2008; 135(2): 165 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Joyce, J. R. Burghardt, R. C. Burghardt, R. N. Hooper, L. A. Jaeger, T. E. Spencer, F. W. Bazer, and G. A. Johnson Pig Conceptuses Increase Uterine Interferon-Regulatory Factor 1 (IRF1), but Restrict Expression to Stroma Through Estrogen-Induced IRF2 in Luminal Epithelium Biol Reprod, August 1, 2007; 77(2): 292 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B A Quinn, M A Hayes, R O Waelchli, M W Kennedy, and K J Betteridge Changes in major proteins in the embryonic capsule during immobilization (fixation) of the conceptus in the third week of pregnancy in the mare Reproduction, July 1, 2007; 134(1): 161 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Song, F. W Bazer, and T. E Spencer Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus Reproduction, January 1, 2007; 133(1): 285 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.P. Hess, A.E. Hamilton, S. Talbi, C. Dosiou, M. Nyegaard, N. Nayak, O. Genbecev-Krtolica, P. Mavrogianis, K. Ferrer, J. Kruessel, et al. Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators Biol Reprod, January 1, 2007; 76(1): 102 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Klein, S. Bauersachs, S. E. Ulbrich, R. Einspanier, H. H.D. Meyer, S. E.M. Schmidt, H.-D. Reichenbach, M. Vermehren, F. Sinowatz, H. Blum, et al. Monozygotic Twin Model Reveals Novel Embryo-Induced Transcriptome Changes of Bovine Endometrium in the Preattachment Period Biol Reprod, February 1, 2006; 74(2): 253 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Gray, C. A. Abbey, P. D. Beremand, Y. Choi, J. L. Farmer, D. L. Adelson, T. L. Thomas, F. W. Bazer, and T. E. Spencer Identification of Endometrial Genes Regulated by Early Pregnancy, Progesterone, and Interferon Tau in the Ovine Uterus Biol Reprod, February 1, 2006; 74(2): 383 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Joyce, F. J. White, R. C. Burghardt, J. J. Muniz, T. E. Spencer, F. W. Bazer, and G. A. Johnson Interferon Stimulated Gene 15 Conjugates to Endometrial Cytosolic Proteins and Is Expressed at the Uterine-Placental Interface throughout Pregnancy in Sheep Endocrinology, February 1, 2005; 146(2): 675 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Spencer, G. A. Johnson, R. C. Burghardt, and F. W. Bazer Progesterone and Placental Hormone Actions on the Uterus: Insights from Domestic Animals Biol Reprod, July 1, 2004; 71(1): 2 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Emond, L. A. MacLaren, S. Kimmins, J. A. Arosh, M. A. Fortier, and R. D. Lambert Expression of Cyclooxygenase-2 and Granulocyte-Macrophage Colony-Stimulating Factor in the Endometrial Epithelium of the Cow Is Up-Regulated During Early Pregnancy and in Response to Intrauterine Infusions of Interferon-{tau} Biol Reprod, January 1, 2004; 70(1): 54 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Okuda, Y. Kasahara, S. Murakami, H. Takahashi, I. Woclawek-Potocka, and D. J. Skarzynski Interferon-{tau} Blocks the Stimulatory Effect of Tumor Necrosis Factor-{alpha} on Prostaglandin F2{alpha} Synthesis by Bovine Endometrial Stromal Cells Biol Reprod, January 1, 2004; 70(1): 191 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kim, Y. Choi, F. W. Bazer, and T. E. Spencer Identification of Genes in the Ovine Endometrium Regulated by Interferon {tau} Independent of Signal Transducer and Activator of Transcription 1 Endocrinology, December 1, 2003; 144(12): 5203 - 5214. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
