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a Center for Animal Biotechnology,
b Institute of Biosciences and Technology, Texas A&M University System Health Center, Departments of Animal Science and
c Veterinary Anatomy & Public Health, Texas A&M University, College Station, Texas 77843-2471
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). Progesterone is required for IFN to exert antiluteolytic actions on the endometrium. Therefore, this study was designed to determine whether progesterone is requisite for IFN induction of UCRP expression within the ovine uterus. Cyclic ewes were ovariectomized and fitted with intrauterine (i.u.) catheters on Day 5 and treated daily with steroids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5–24) and control serum proteins (CX, Days 11–24); 2) P and ZK 137.316 (ZK; progesterone receptor antagonist, Days 11–24) and CX proteins; 3) P and recombinant ovine IFN (roIFN, Days 11–24); or 4) P and ZK and roIFN. All ewes were hysterectomized on Day 25. In P-treated ewes, roIFN increased endometrial UCRP mRNA and protein levels. However, administration of ZK to ewes ablated roIFN induction of UCRP. Recombinant ovine IFN induced expression of UCRP mRNA in progestinized endometrial luminal (LE) and glandular (GE) epithelium as well as in both stratum compactum and spongiosum layers of the stroma (ST). Progesterone receptor protein was located in endometrial ST, but not in LE and GE from these ewes. Results support the hypothesis that progesterone is required for IFN induction of type I IFN-responsive genes, such as UCRP, in the ruminant uterus.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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) between Days 9 and 24 of pregnancy [1]. IFN acts in a paracrine manner to suppress transcription of estrogen receptor alpha and oxytocin receptor (OTR) gene expression in the endometrial luminal epithelium (LE) and superficial glandular epithelium (GE) of the uterine endometrium [2]. Consequently, OTR do not form on the endometrial LE and superficial GE [3], and oxytocin-induced release of luteolytic prostaglandin F2
(PGF2) pulses are abrogated to maintain the corpus luteum and production of progesterone [4]. Progesterone is required for establishment and maintenance of an embryotrophic uterine environment [5].
In addition to regulating PGF2 release, IFN induces de novo synthesis and secretion of ubiquitin cross-reactive protein (UCRP) [6, 7]. In the ewe, uterine UCRP mRNA is detectable in the LE, stratum compactum of the stroma (ST), and shallow GE on Day 13 of pregnancy; then expression extends to the deep GE, stratum spongiosum of the ST, and myometrium of the uterus by Day 15 [7]. The inferred amino acid sequence from the cDNA encoding ovine UCRP shares 87% identity with bovine interferon-stimulated gene 17 (ISG17; or UCRP), 64% identity with huISG15, and 31% identity with a tandem ubiquitin repeat, and it conserves the Leu-Arg-Gly-Gly (LRGG) C-terminal sequence of ubiquitin that ligates to and directs degradation of cytosolic proteins in vivo (personal communication with A.M. Collins, K.J. Austin, A.D. Ealy, C.-S. Han, and T.R. Hansen, University of Wyoming, Laramie, WY). Bovine UCRP conjugates to endometrial cytosolic proteins [8]. It has been proposed that the regulation and/or degradation of endometrial proteins by UCRP favors the establishment and maintenance of pregnancy in ruminants [8].
IFN is secreted into a uterine environment that is under the developmental and functional regulation of ovarian steroids. Concentrations of progesterone in peripheral blood peak with maturation of the corpus luteum, and progesterone is required for IFN to exert antiluteolytic actions on the endometrium [9]. Progesterone stimulates transformation of the endometrium into a secretory tissue to create an environment permissive to early embryonic development, implantation, placentation, and fetal/placental development [5]. Administration of progesterone to recipient cows early in the estrous cycle advances uterine functions and receptivity for transfer of older asynchronous embryos [10]. Since progesterone is required for the antiluteolytic actions of IFN on the endometrium [9], progesterone may also be required for IFN regulation or induction of type I IFN-responsive genes. Therefore, experiments were conducted to test the hypothesis that progesterone is requisite for UCRP induction by IFN within the ovine uterus.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Experimental and surgical procedures involving animals were approved by the Institutional Agricultural Animal Care and Use Committee of Texas A&M University (Animal Use Protocol AG-239AG). Mature Western-range ewes of primarily Rambouillet breeding were observed daily for estrous behavior using vasectomized rams, and they exhibited at least two estrous cycles of normal duration (16–18 days) before experimental manipulation. As summarized in Figure 1A, 16 cyclic ewes (Day 0 = estrus) were ovariectomized, fitted with uterine catheters [11], and randomly assigned (n = 4 ewes per treatment) to receive daily i.m. injections of steroids and intrauterine (i.u.) injections of protein as follows: 1) 50 mg progesterone (P, Days 5–24) and 200 µg control serum proteins (CX; ovine serum proteins, Days 11–24; P-CX); 2) P plus 75 mg ZK 137.312 (ZK; progesterone receptor antagonist; generously provided by Dr. Kristoff Chwalisz, Schering, AG, Berlin, Germany, Days 11–24) and CX proteins (P+ZK-CX); 3) P and recombinant ovine IFN (roIFN; 2 x 107 antiviral units, Days 11–24; P-IFN) [12]; or 4) P, ZK, and roIFN (P+ZK-IFN). Both uterine horns of each ewe received twice-daily (0700 h and 1900 h) injections of either CX protein (50 µg/horn/injection) or roIFN (5 x 106 antiviral units/horn/injection). Steroids were administered daily (0700 h) in a total volume of 1 ml corn oil vehicle. All ewes were hysterectomized on Day 25. Several sections (1–1.5 cm) of the uterine wall from the middle portion of each uterine horn were fixed in fresh 4% paraformaldehyde in PBS (pH 7.2). The remaining endometrium was dissected from myometrium and frozen in liquid nitrogen.
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Slot Blot Hybridization Analysis
Total cellular RNA was isolated from frozen endometrium using Trizol reagent (Gibco-BRL, Grand Island, NY). For each ewe, denatured total cellular RNA (20 µg) was hybridized with radiolabeled antisense bovine UCRP (the 605-base pair [bp] cDNA was kindly provided by Dr. Thomas R. Hansen, University of Wyoming, Laramie, and contains the entire coding sequence for bUCRP) [13] or 18S rRNA (pT718S; Ambion, Austin, TX) cRNA probes generated by in vitro transcription with [-32P]UTP (Amersham) as previously described [14]. Radioactivity in each slot was quantified by electronic autoradiography using an Instant Imager (Packard, Meriden, CT) and expressed as total counts.
In Situ Hybridization Analysis
UCRP mRNA was localized in paraffin-embedded uterine tissue sections by in situ hybridization as previously described [7]. Deparaffinized, rehydrated, and deproteinated uterine sections (4–8 µm) were hybridized with radiolabeled antisense or sense bovine UCRP [12] probes using in vitro transcription with [-35S]UTP. Autoradiography was performed using Kodak (Eastman Kodak, Rochester, NY) NTB-2 liquid photographic emulsion [15]. Slides were exposed at 4°C for 5 days, developed in Kodak D-19 developer, counterstained with Harris' modified hematoxylin (Fisher Scientific, Fairlawn, NJ), dehydrated through a graded series of alcohol to xylene, and coverslipped.
Western Blot Analysis
Endometrium was thawed and homogenized, and the concentration of protein was determined using a Bradford protein assay (Bio-Rad Laboratories, Hercules, CA) as previously described [7]. Proteins in endometrial extracts (100 µg) were denatured in Laemmli buffer, separated on 12% (total monomer) one-dimensional (1D) SDS-PAGE gels, and transferred to nitrocellulose as previously described [16]. Blots were then blocked and incubated with polyclonal rabbit anti-human UCRP serum (5 µg/ml, kindly provided by Dr. Ernest Knight Jr., E.I. du Pont de Nemours and Company, Inc., Wilmington, DE) [17] followed by goat anti-rabbit IgG horseradish peroxidase conjugate (1:15 000 dilution of 1 mg/ml stock; KPL, Bethesda, MD), and immunoreactive proteins were detected using enhanced chemiluminescence (Amersham Life Sciences, Arlington Heights, Rochester, NY) as previously described [7].
Immunohistochemistry
Progesterone receptor (PR) protein was localized in paraffin-embedded uterine tissue sections using a mouse monoclonal antibody against human PR (MA1–411; Affinity Bioreagents, Golden, CO) and a Super ABC Mouse/Rabbit IgG Kit (Biomeda, Foster City, CA) as previously described [18]. Sections (5–7 µm) were deparaffinized, rehydrated to water, subjected to heated citrate buffer antigen retrieval, and then incubated with anti-PR IgG (5 µg/ml) or mouse IgG (5 µg/ml; Sigma, St. Louis, MO). Immunoreactive protein was visualized using diaminobenzidine tetrahydrochloride (Sigma) as the chromagen. Sections were counterstained with hematoxylin, dehydrated, and coverslipped over Permount (Fisher Scientific, Pittsburgh, PA).
Photomicroscopy
Photomicrographs of representative fields of in situ hybridization and immunocytochemistry slides were evaluated under brightfield (immunocytochemistry) or under both brightfield and darkfield (in situ) illumination with a Zeiss Axioplan2 microscope fitted with a Hamamatsu chilled 3CCD color camera (Carl Zeiss Inc., Thornwood, NY). Digital images were captured using Adobe Photoshop 4.0 (Adobe Systems, Seattle, WA) and MacIntosh PowerMac G3 computer (Apple Computer, Cupertino, CA).
Statistical Analyses
Data were subjected to least-squares analysis of variance (LS-ANOVA) using General Linear Models procedures of the Statistical Analyses System [19]. Slot blot hybridization data (total counts) were analyzed using the 18S rRNA as a covariate in LS-ANOVA. Preplanned orthogonal contrasts (P-CX vs. P-IFN; P+ZK-CX vs. P-CX; P+ZK-IFN vs. P-IFN) were used to test effects of treatment [20]. All tests of significance were performed using the appropriate error terms according to the expectation of the mean squares for error. Data are presented as least-squares means with standard errors.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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As illustrated in Figure 1B, intrauterine administration of roIFN increased UCRP mRNA approximately 4-fold in progesterone-treated endometrium (P-CX versus P-IFN, P < 0.01). Treatment of controls with ZK did not affect UCRP mRNA expression (P-CX versus P+ZK-CX, P > 0.10). However, administration of ZK to ewes receiving progesterone and roIFN ablated IFN stimulation of UCRP mRNA expression in the endometrium (P-IFN versus P+ZK-IFN, P < 0.01).
In Situ Localization of UCRP mRNA
IFN and progesterone induced expression of UCRP mRNA in endometrial LE and GE, as well as in both stratum compactum and spongiosum layers of the ST (Fig. 2). UCRP mRNA was not detectable in the absence of roIFN or in endometrium of ewes treated with ZK (Fig. 2).
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Western Blot Analysis of UCRP Protein
Western blot analysis of endometrial extracts (Fig. 3) revealed induction of UCRP (17 kDa) by roIFN and progesterone. Levels of endometrial UCRP were decreased in ewes that received ZK (Fig. 3). Ubiquitin protein (8 kDa) expression was not affected by in vivo treatments.
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Immunocytochemical Localization of PR Protein
Nuclear PR was not evident in either the endometrial LE or GE of ewes that received progesterone alone (P-CX or P-IFN), whereas nuclear PR was present in the endometrial LE and GE of ewes that received ZK (Fig. 4). PR was present in endometrial ST of all ewes examined regardless of in vivo treatment (Fig. 4).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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, the pregnancy recognition signal [1]. IFN also increases production and/or secretion of several endometrial proteins that may be integral to the establishment of early pregnancy in the ewe [21]. UCRP mRNA is present in ovine endometrium from Days 13 to 25 of pregnancy; the protein increases in endometrium and uterine flushings after Day 12, and UCRP is induced by roIFN both in vitro (endometrial explant or cell culture) and in vivo (intrauterine injection) [7]. Results of the present study demonstrate that interaction between progesterone and its receptor (PR) is required for IFN induction of UCRP within the ovine uterus. As expected, administration of roIFN to progesterone-treated ovariectomized ewes induced expression of UCRP mRNA and protein within endometrial tissues. However, administration of a PR antagonist abolished the ability of roIFN to induce UCRP levels above those for controls that did not receive IFN. Similar results have been reported for the IFN-induced Mx gene [22], but this is the first report to describe ovarian steroid regulation of UCRP induction by IFN in any species.
Presumably IFN induces transcription factors that then bind to the UCRP gene promotor. The promotors for huISG15 (human UCRP gene) and boISG17 (bovine UCRP gene) contain two and five interferon-stimulated response elements, respectively [23, 24]. The pathway by which progesterone regulates IFN induction of UCRP mRNA in the ovine endometrium is unknown. In general, progesterone actions in target tissues are poorly understood, and their elucidation is complicated by possible direct and indirect effects of progesterone on endometrial cells [25]. Direct interaction of PR with the UCRP gene promotor is unlikely because UCRP mRNA is not expressed in cyclic ewes [7], and the bovine gene and promotor sequence, including 1180 bp upstream, does not have a hormone response element for progesterone [24].
It should be emphasized that as a result of progesterone administration for 25 days, PR were absent in endometrial LE and GE (Fig. 4). Yet, as in pregnancy [7], these PR-negative epithelia were able to respond to IFN and express UCRP mRNA. However, when a PR antagonist was used to block the progesterone-induced down-regulation of epithelial cell PR as well as the actions of ST cell PR, induction of UCRP mRNA by IFN was ablated (see Fig. 2). These results may indicate that regulation of UCRP mRNA expression in LE and GE requires both a progesterone-induced paracrine factor(s) produced by PR-positive stromal cells, and IFN. If so, the PR antagonist would prevent PR activation by progesterone and subsequent release of a stromal-derived paracrine factor essential for UCRP expression. Although IFN binds all accessible type I IFN receptors on LE and shallow GE, UCRP gene transcription does not occur in ZK-treated ewes because of the absence of the progesterone-induced paracrine factor. In turn, IFN may be unable to induce basolateral secretion from the epithelium of a possible IFN-induced factor(s) that may act as a paracrine stimulator of IFN responses in ST [7, 26, 27]. The result is ablation of UCRP mRNA expression throughout the entire endometrial wall (see Fig. 2).
Paracrine mediation of steroid-induced epithelial responses by steroid receptors in the underlying stroma has been suggested previously. Bigsby and Cunha [28] proposed that estrogen receptors in ST cells are responsible for estrogen stimulation of uterine epithelial proliferation within neonatal mice. Using PR knockout mice [29], researchers at the same laboratory demonstrated that the inhibitory effect of progesterone on estrogen-induced murine uterine epithelial proliferation is mediated by stromal and not epithelial PR [30]. Interestingly, hepatocyte growth factor (HGF) and fibroblast growth factor-10 (FGF-10), which are proposed mediators of stromal to epithelial cell signaling [31, 32], as well as their respective receptors c-met and kerotinocyte growth factor receptor (KGFR), are expressed in the ovine uterus [33]. HGF and FGF-10 mRNA are expressed by ST cells, whereas c-met and KGFR mRNA are unique to uterine LE and GE [33].
In response to conceptus-derived IFN, the progesterone-stimulated ovine uterus expresses UCRP as part of a sequence of events considered to favor early embryonic development and survival. The role of UCRP in development of an endometrium receptive to the conceptus is unknown. As a functional ubiquitin homolog, UCRP can conjugate to intracellular proteins and target their degradation within a protease complex called the proteasome [10, 34, 35]. However, all conjugated proteins are not destined for proteasomal degradation. Proteins are often stabilized or activated, or their functions are altered, by the conjugation pathway [36–38]. Ubiquitin conjugation can also influence gross cell physiology. For example, neurite outgrowth from rat PC12 cells is promoted by enhanced rates of ubiquitin-protein conjugate synthesis, rather than degradation [39]. Specific UCRP ligation partners are not known. Possible candidates include uterine proteins that are involved in PGF2 release [40], transcription factors regulating genes encoding proteins [41, 42], immunoregulatory elements within the uterus [43], or intracellular proteins involved in apposition, attachment, and adhesion of the trophoblast to the uterine LE [44].
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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1 Research supported in part by USDA-NRICGP 95-37203-2185 to F.W.B. and R.C.B. 
2 Correspondence: Fuller W. Bazer, Department of Animal Science and Center for Animal Biotechnology and Genomics, 442D Kleberg Center, Texas A&M University, College Station, TX 77843-2471. FAX: 409 862 2662; fbazer{at}cvm.tamu.edu
Accepted: October 19, 1999.
Received: September 9, 1999.
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REFERENCES |
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from the ovine uterus during luteolysis and its abrogation in early pregnancy. Anim Reprod Sci 1984; 7:31–55.) alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes. J Mol Endocrinol 1995; 15:203–220.) alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes. J Mol Endocrinol 1995; 15:203–220.). Biol Reprod 1999; 60(suppl 1):211 (abstract 379).
B1 precursor protein and the activation of NF-B. Cell 1994; 78:773–785.[CrossRef][Medline] regulates expression of endometrial receptors for estrogen and oxytocin but not progesterone. Biol Reprod 1995; 53:732–745.[Abstract]This article has been cited by other articles:
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  H. Gao, G. Wu, T. E. Spencer, G. A. Johnson, and F. W. Bazer Select Nutrients in the Ovine Uterine Lumen. IV. Expression of Neutral and Acidic Amino Acid Transporters in Ovine Uteri and Peri-Implantation Conceptuses Biol Reprod, June 1, 2009; 80(6): 1196 - 1208. [Abstract] [Full Text] [PDF]
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 G. Song, M C. Satterfield, J. Kim, F. W Bazer, and T. E Spencer Progesterone and interferon tau regulate leukemia inhibitory factor receptor and IL6ST in the ovine uterus during early pregnancy Reproduction, March 1, 2009; 137(3): 553 - 565. [Abstract] [Full Text] [PDF]
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H. Gao, G. Wu, T. E. Spencer, G. A. Johnson, and F. W. Bazer Select Nutrients in the Ovine Uterine Lumen. III. Cationic Amino Acid Transporters in the Ovine Uterus and Peri-Implantation Conceptuses Biol Reprod, March 1, 2009; 80(3): 602 - 609. [Abstract] [Full Text] [PDF]
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C.A. Gifford, A.M. Assiri, M.C. Satterfield, T.E. Spencer, and T.L. Ott Receptor Transporter Protein 4 (RTP4) in Endometrium, Ovary, and Peripheral Blood Leukocytes of Pregnant and Cyclic Ewes Biol Reprod, September 1, 2008; 79(3): 518 - 524. [Abstract] [Full Text] [PDF]
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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]
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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]
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Y. Chen, E. Antoniou, Z. Liu, L. B Hearne, and R M. Roberts A microarray analysis for genes regulated by interferon-{tau} in ovine luminal epithelial cells Reproduction, July 1, 2007; 134(1): 123 - 135. [Abstract] [Full Text] [PDF]
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 C. A. Gifford, K. Racicot, D. S. Clark, K. J. Austin, T. R. Hansen, M. C. Lucy, C. J. Davies, and T. L. Ott Regulation of Interferon-Stimulated Genes in Peripheral Blood Leukocytes in Pregnant and Bred, Nonpregnant Dairy Cows J Dairy Sci, January 1, 2007; 90(1): 274 - 280. [Abstract] [Full Text] [PDF]
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M. H. Melner, A. L. Haas, J. M. Klein, A. R. Brash, W. E. Boeglin, S. K. NagDas, V. P. Winfrey, and G. E. Olson Demonstration of Ubiquitin Thiolester Formation of UBE2Q2 (UBCi), a Novel Ubiquitin-Conjugating Enzyme with Implantation Site-Specific Expression Biol Reprod, September 1, 2006; 75(3): 395 - 406. [Abstract] [Full Text] [PDF]
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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]
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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]
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K. J. Austin, A. L. Carr, J. K. Pru, C. E. Hearne, E. L. George, E. L. Belden, and T. R. Hansen Localization of ISG15 and Conjugated Proteins in Bovine Endometrium Using Immunohistochemistry and Electron Microscopy Endocrinology, February 1, 2004; 145(2): 967 - 975. [Abstract] [Full Text] [PDF]
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M. H. Melner, N. A. Ducharme, A. R. Brash, V. P. Winfrey, and G. E. Olson Differential Expression of Genes in the Endometrium at Implantation: Upregulation of a Novel Member of the E2 Class of Ubiquitin-Conjugating Enzymes Biol Reprod, February 1, 2004; 70(2): 406 - 414. [Abstract] [Full Text] [PDF]
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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]
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Y. Choi, G. A. Johnson, T. E. Spencer, and F. W. Bazer Pregnancy and Interferon Tau Regulate Major Histocompatibility Complex Class I and {beta}2-Microglobulin Expression in the Ovine Uterus Biol Reprod, May 1, 2003; 68(5): 1703 - 1710. [Abstract] [Full Text] [PDF]
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Y. Choi, G. A. Johnson, R. C. Burghardt, L. R. Berghman, M. M. Joyce, K. M. Taylor, M. David Stewart, F. W. Bazer, and T. E. Spencer Interferon Regulatory Factor-Two Restricts Expression of Interferon-Stimulated Genes to the Endometrial Stroma and Glandular Epithelium of the Ovine Uterus Biol Reprod, October 1, 2001; 65(4): 1038 - 1049. [Abstract] [Full Text] [PDF]
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J.-A. G. W. Fleming, Y. Choi, G. A. Johnson, T. E. Spencer, and F. W. Bazer Cloning of the Ovine Estrogen Receptor-{{alpha}} Promoter and Functional Regulation by Ovine Interferon-{{tau}} Endocrinology, July 1, 2001; 142(7): 2879 - 2887. [Abstract] [Full Text] [PDF]
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M. D. Stewart, G. A. Johnson, F. W. Bazer, and T. E. Spencer Interferon-{{tau}} (IFN{{tau}}) Regulation of IFN-Stimulated Gene Expression in Cell Lines Lacking Specific IFN-Signaling Components Endocrinology, May 1, 2001; 142(5): 1786 - 1794. [Abstract] [Full Text]
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G. A. Johnson, M. D. Stewart, C. Allison Gray, Y. Choi, R. C. Burghardt, L.-Y. Yu-Lee, F. W. Bazer, and T. E. Spencer Effects of the Estrous Cycle, Pregnancy, and Interferon Tau on 2',5'-Oligoadenylate Synthetase Expression in the Ovine Uterus Biol Reprod, May 1, 2001; 64(5): 1392 - 1399. [Abstract] [Full Text]
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J. K. Pru, B. R. Rueda, K. J. Austin, W. W. Thatcher, A. Guzeloglu, and T. R. Hansen Interferon-Tau Suppresses Prostaglandin F2{{alpha}} Secretion Independently of the Mitogen-Activated Protein Kinase and Nuclear Factor {{kappa}} B Pathways Biol Reprod, March 1, 2001; 64(3): 965 - 973. [Abstract] [Full Text]
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G. A. Johnson, T. E. Spencer, R. C. Burghardt, K. M. Taylor, C. A. Gray, and F. W. Bazer Progesterone Modulation of Osteopontin Gene Expression in the Ovine Uterus Biol Reprod, May 1, 2000; 62(5): 1315 - 1321. [Abstract] [Full Text]
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