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Articles |
a Center for Animal Biotechnology and Genomics,
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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) may regulate OPN expression in the uterine GE. 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 136.317 (ZK; progesterone receptor [PR] 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. Progesterone induced the expression of endometrial OPN mRNA in the GE and increased secretion of a 45-kDa OPN protein from endometrial explants maintained in culture for 24 h. Administration of ZK ablated progesterone effects. Intrauterine infusion of roIFN did not affect OPN gene expression or secretion in any of the steroid treatments. Interestingly, OPN mRNA-positive GE cells lacked detectable PR expression, although PR were detected in the stroma. Results indicate that progesterone regulates OPN expression in GE through a complex mechanism that includes PR down-regulation, and we suggest the possible involvement of a progesterone-induced stromal cell-derived growth factor(s) that acts as a progestamedin.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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vß3, vß1, vß5, and 4ß1 integrin heterodimers via its Arg-Gly-Asp (RGD) sequence [8–10] to promote cell adhesion, spreading, and migration [11]. It also stimulates calcium transport and phosphatidylinositol 3'-kinase activity [5, 12]. During the periimplantation period, the endometrial glands produce histotroph that nourishes and sustains the conceptus (embryo and associated membranes) [13]. It is hypothesized that these secretions support conceptus remodeling, adhesion, implantation, and placentation. OPN is a component of histotroph because it increases in uterine flushings from pregnant ewes between Days 11 and 17 [6], a period that corresponds to the adherence and attachment phases of early implantation. Secreted OPN may then bind integrin heterodimers expressed by trophectoderm and uterus to 1) stimulate changes in morphology of conceptus extraembryonic placental membranes and 2) induce adhesion between luminal epithelium (LE) and trophectoderm essential for implantation and placentation [6]. Although OPN mRNA increases only in the endometrial glandular epithelium (GE) of pregnant ewes [14], OPN protein is localized on the apical aspect of the endometrial LE, GE, and conceptus trophectoderm [6].
While the temporal and spatial expression of OPN during the ovine estrous cycle and pregnancy has been described [6, 14], it is not yet clear whether the regulation of OPN gene expression and/or secretion by GE is controlled by progesterone and/or interferon-tau (IFN). In the present study, a well-characterized steroid-treated uterine-infused ovariectomized ewe model [15] was utilized to elucidate the regulation of OPN gene expression and protein secretion by GE.
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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 had exhibited at least two estrous cycles of normal duration (16–18 days) prior to experimental manipulation. Sixteen cyclic ewes (Day 0 = estrus) were ovariectomized and fitted with uterine catheters on Day 5 [15] and then assigned randomly (n = 4 ewes per treatment) to receive daily i.m. injections of steroids and intrauterine (i.u.) infusions 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); 2) P and 75 mg ZK 137.316 (ZK; progesterone receptor antagonist, Days 11–24; generously provided by Dr. Kristof Chwalisz, Schering AG, Berlin, Germany) and CX proteins; 3) P and recombinant ovine IFN (roIFN; 2 x 107 antiviral units, Days 11–24) [16]; or 4) P and ZK and IFN. The experimental design is summarized in Figure 1A. Both uterine horns of each ewe received twice-daily (0700 h and 1900 h) infusions of either CX protein (50 µg/horn per injection) or IFN (5 x 106 antiviral units/horn per injection). Steroids were administered daily (0700 h) in a total volume of 1 ml corn oil vehicle. All ewes were hysterectomized on Day 25.
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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) or snap frozen in Tissue-Tek OCT compound (Miles, Oneata, NY). The remaining endometrium was dissected from myometrium and frozen in liquid nitrogen or placed into warm Dulbecco's modified Eagle's medium (DMEM)/F12 culture medium (Sigma, St. Louis, MO) for explant culture. Endometrial explant cultures, derived from fresh endometrium (500 mg/culture) that was minced with scalpel blades into small pieces (2–3 cubic mm), were placed into culture dishes (100 x 15 mm) with 5 ml of DMEM/F12 culture medium containing penicillin G (100 IU/ml), streptomycin (0.1 mg/ml), and amphotericin B (0.25 µg/ml; Gibco-BRL, Grand Island, NY). Cultures were incubated for 24 h with rocking under an atmosphere of 45% nitrogen, 5% carbon dioxide, and 50% oxygen.
Slot-Blot Hybridization Analysis
Total cellular RNA was isolated from frozen endometrium using Trizol reagent (Gibco-BRL). For each ewe, denatured total cellular RNA (20 µg) was hybridized with radiolabeled antisense ovine OPN [14] or 18S rRNA (pT718S; Ambion, Austin, TX) cRNA probes generated by in vitro transcription with [-32P]UTP (Amersham Pharmacia Biotech, Piscataway, NJ) as previously described [15]. 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
OPN mRNA was localized in paraffin-embedded uterine tissue sections by in situ hybridization analysis as previously described [14]. Deparaffinized, rehydrated, and deproteinated uterine sections (4–8 µm) were hybridized with radiolabeled antisense or sense ovine OPN cRNA probes using in vitro transcription with [-35S]UTP. Autoradiography was performed using Kodak (Eastman Kodak, Rochester, NY) NTB-2 liquid photographic emulsion and exposed at 4°C for 5 days (as judged by autoradiographs), developed, counterstained with Harris' modified hematoxylin (Fisher Scientific, Fairlawn, NJ), dehydrated through a graded series of alcohol to xylene, and coverslipped [17].
Western Blot Analysis
Endometrium was thawed and homogenized, and concentration of protein was determined [6]. The medium from explant cultures was harvested and dialyzed, and protein concentrations were determined using a Bradford protein assay (Bio-Rad Laboratories, Hercules, CA) as previously described [9]. Proteins in endometrial extracts (100 µg) or explant culture medium (60 µg) were denatured in Laemmli buffer, separated on 10% (total monomer) SDS-PAGE gels, and transferred to nitrocellulose [18]. Blots were then blocked, incubated with a cocktail containing rabbit polyclonal antibodies against recombinant human OPN (anti-hOPN; LF-123 and LF-124; 5 µg/ml, generously provided by Dr. Marian F. Young, NIH, Bethesda, MD) [19] or normal rabbit serum (5 µg/ml) followed by incubation with goat anti-rabbit IgG horseradish peroxidase conjugate (1:15 000 dilution of 1 mg/ml stock; KPL, Bethesda, MD). Immunoreactive proteins were detected using enhanced chemiluminescence (Amersham Life Sciences, Rochester, NY) as previously described [6].
Immunohistochemistry
OPN protein was localized in frozen uterine tissue sections (4–8 µm) by immunofluorescence staining as previously described [6]. Frozen sections were fixed in -20°C methanol, permeabilized with 0.3% Tween 20 in 0.02 M PBS, blocked in 5% normal goat serum, and incubated overnight at 4°C with 20 µg/ml rabbit IgG against human OPN (LF-123 and LF-124) [19]. Immunoreactive protein was then detected using a fluorescein-conjugated goat anti-rabbit IgG (Zymed, San Francisco, CA). Coverslips were placed over a layer of Prolong antifade mounting reagent (Molecular Probes, Eugene, OR).
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 [20]. 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). Immunoreactive protein was visualized using diaminobenzidine tetrahydrochloride (Sigma) as the chromogen. Sections were counterstained with hematoxylin, dehydrated, and coverslipped over Permount (Fisher Scientific, Pittsburg, PA).
Photomicroscopy
Photomicrographs of representative fields of in situ hybridization slides were evaluated under brightfield and darkfield illumination with a Zeiss Axioplan2 microscope fitted with a Hamamatsu chilled 3CCD color camera (Carl Zeiss, Thornwood, NY). Digital images were captured using Adobe Photoshop 4.0 (Adobe Systems, Seattle, WA) and MacIntosh PowerMac G3 computer (Apple Computer, Cupertino, CA). Prints were generated electronically using a Kodak DS8650 color printer. Photomicrographs of representative fields of immunofluorescence slides were photographed in brightfield with a Zeiss Photomicroscope III (Carl Zeiss) on T-Max 3200 film (Kodak).
Statistical Analyses
Data were subjected to least squares (LS)-ANOVA using the General Linear Models procedures of the Statistical Analysis System [21]. 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 for effects of treatment [22]. 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-square means with SE.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The contributions of progesterone and/or IFN to endometrial OPN mRNA expression were examined in ovariectomized ewes subjected to the treatment regimen summarized in Figure 1A. Slot-blot hybridization analysis (Fig. 1B) revealed that progesterone increased steady-state levels of endometrial OPN mRNA while the PR antagonist ZK suppressed this response (P-CX vs. P+ZK-CX, P < 0.01; P-IFN vs. P+ZK-IFN, P < 0.01). In contrast, i.u. administration of roIFN had no effect on OPN mRNA expression regardless of steroid treatments (P-CX vs. P-IFN, P > 0.10; P+ZK-CX vs. P+ZK-IFN, P > 0.10).
In Situ Hybridization Analysis of OPN mRNA
In uteri of P-CX and P-IFN ewes, OPN mRNA was localized only in the endometrial GE of the stratum spongiosum (Fig. 2). In contrast, OPN mRNA was not detected in GE of P+ZK-treated ewes regardless of i.u. protein treatment. In uteri from all ewes, OPN mRNA was observed in clusters of immune cells that were distributed in an intermittent pattern within the uterine stroma (Fig. 3). The majority of these OPN mRNA-positive cells were located in the stratum compactum; however, immune cells were observed in only a small percentage of the total stratum compactum. The number and distribution of these cells were not affected by steroid or i.u. protein treatment (data not shown).
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Immunofluorescent Localization of OPN Protein
Immunoreactive OPN was detected at the apical surface of both LE and GE of all ewes examined regardless of in vivo treatment (Fig. 4). OPN was not present in the endometrial stroma, myometrium, or blood vessels. Controls in which rabbit IgG replaced anti-hOPN primary antibody showed no cross-reacting protein at the apical surface of the endometrial epithelium.
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Western Blot Analysis of OPN Protein in Endometrial Extracts and Explant Culture Medium
Immunoreactive 70-, 45-, and 25-kDa OPN proteins were detected in endometrial extracts from all ewes examined (Fig. 5A), but there were no effects of steroid or protein treatment on the pattern or intensity of immunoreactive proteins. As shown in Figure 5B, the 45- and 25-kDa OPN forms were detected predominantly in endometrial explant culture medium. Levels of the 45-kDa OPN were dramatically reduced in culture medium from ewes receiving ZK (Fig. 5B).
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Immunocytochemical Localization of PR Protein
Nuclear PR was not evident in either endometrial LE or GE of ewes that received P alone (P-CX or P-IFN), whereas nuclear PR was present in endometrial LE and GE of ewes that received ZK (Fig. 6). PR were present in endometrial ST of all ewes examined regardless of in vivo treatment (Fig. 6).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Uterine stromal cell mediation of epithelial cell function has been demonstrated. Bigsby and Cunha (1986) [27] proposed that estrogen receptors in uterine stromal cells are required for estrogen to induce uterine epithelial cell proliferation in neonatal mice. Using PR knockout mice [28], the same laboratory demonstrated that the inhibitory effect of progesterone on estrogen-induced murine uterine epithelial proliferation is mediated via stromal PR and not epithelial PR [29]. Keratinocyte growth factor/fibroblast growth factor-7 (KGF/FGF-7) is a candidate stromal-to-epithelial cell mediator of proliferation, because KGF injections stimulate proliferation of uterine epithelium [30] and KGF is considered a stromal cell-derived progestamedin in the primate endometrium [31]. Hepatocyte growth factor (HGF), another proposed mediator of stromal-to-epithelial cell signaling [32], may modulate regeneration of the human endometrium after menstruation [33]. There is recent evidence that HGF, FGF-7, and FGF-10, as well as their respective receptors, c-met and KGF receptor (KGFR), are present in the ovine uterus [34]. HGF and FGF-10 mRNA are expressed predominately by stromal cells of the stratum compactum of the ovine uterine endometrium, whereas c-met and KGFR mRNA are detected only in LE and GE [34].
OPN mRNA was also detected in randomly distributed groups of cells within the stroma, regardless of steroid or protein treatment; the majority of these scattered cells were in the stratum compactum (Fig. 3). The apparent cell morphology and intermittent spacing of these cells within the endometrium, combined with evidence for OPN expression by T-lymphocytes, monocytes, macrophages, and natural killer cells, provide indirect evidence that these are immune cells [35–37]. Expression and secretion of OPN by these cells may explain accumulation of OPN on the uterine LE of all ewes regardless of treatment (Fig. 4), as well as the constitutive presence of OPN protein in endometrial extracts (Fig. 5A). A wide array of epithelia express OPN [4]. Perhaps OPN has a long life span on the cell surface and is maintained on the LE of cyclic ewes to maximize uterine receptivity to potential conceptus attachment.
Expression of OPN within the ovine uterine environment may be further regulated by posttranslational modification of the secreted protein. OPN is a 70-kDa protein that gives rise to 45- and 25-kDa fragments upon freezing and thawing or by treatment with proteases [38]. During the ovine estrous cycle and early pregnancy, three forms of OPN are detected in endometrial cytosolic extracts [6]. In this study, endometrial extracts also possessed 70-, 45-, and 25-kDa immunoreactive forms of OPN that did not vary with treatment (Fig. 5A). However, Western blots of endometrial explant culture medium detected predominantly the 45- and 25-kDa OPN forms (Fig. 5B). These results agree with those from analyses of uterine flushings from cyclic and pregnant ewes [6] and suggest differential cleavage of secreted OPN. Of particular interest is the dramatic decrease in the 45-kDa OPN form in explant cultures derived from ewes that received ZK (Fig. 5B). This 45-kDa form of OPN binds with higher affinity to vß3 integrins and has greater biological activity than the native 70-kDa form [39]. However, it is susceptible to degradation into smaller 20- to 30-kDa fragments [40]. Progesterone may regulate production of factors, such as tissue inhibitors of metalloproteinases [41], that prevent degradation of the 45-kDa OPN, and thereby maintain the presence of this biologically active OPN in the uterine lumen of pregnant ewes. Increased levels of the 45-kDa OPN may be significant regarding interactions of OPN within the periimplantation conceptus and uterine epithelia.
Implantation is a progressive process involving adhesion molecule-dependent remodeling of endometrium and trophectoderm [42]. The GRGDS sequence of OPN suggests interactions with cell surface integrins [43]. Integrins are the dominant molecules in adhesion cascades since they can bind their extracellular matrix ligand(s) to mediate adhesion (implantation), cytoskeletal reorganization to stabilize adhesion (elongation of conceptuses), and transduction of cellular signals through numerous signaling intermediates [44]. Indeed, human smooth muscle cells adhere and migrate to OPN in culture [11]. OPN binding to vß3 integrins results in rapid phosphoinositide turnover and inositol trisphosphate production [12], alterations in cytosolic calcium [45], and increased angiogenesis [46]. Expression of OPN in the reproductive tracts of several species has been established. OPN is expressed by murine metrial gland cells of the decidua, trophoblast, and placenta [47]. Likewise, OPN is expressed at high levels by invading cytotrophoblast of the chorionic villus, endometrial GE of secretory-phase uteri, and decidualizing stromal cells of baboons and humans [3, 4, 48]. In ruminants, OPN is present in the bovine oviductal epithelium and luminal fluid [7], whereas OPN protein has been detected on ovine endometrial LE and in uterine flushings [6].
Collectively, results from human and rodent models indicate that OPN secreted by uterine epithelia binds integrins on luminal surfaces, and that this interaction is important for LE communication with the external environment [4]. In ewes, secretion of OPN by uterine GE [6, 14], along with the presence of v, 4, 9, ß1, ß3, and ß9 integrin ligand on trophectoderm and uterine LE (unpublished results), indicates a possible role for OPN in apposition, attachment, and adhesion of the trophoblast to the uterine LE. Results of the present studies indicate that OPN mRNA expression in the ovine uterus is induced by progesterone and leads to secretion of OPN into the uterine lumen by GE. We hypothesize that OPN then binds integrins expressed by trophectoderm and uterine epithelia to 1) stimulate changes in morphology of trophectoderm and extraembryonic endoderm that result in elongation of the conceptus and 2) induce adhesion between LE and trophectoderm essential for attachment and superficial implantation.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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1 Research supported by USDA-NRICGP 95–37203-2185 to F.W.B. and R.C.B., and by NIH 1-F32-HD08501-01A1 to G.A.J. 
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: December 17, 1999.
Received: October 20, 1999.
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REFERENCES |
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vß3 integrin expression in the uterus and conceptus during the periimplantation period. Biol Reprod 1999; 61:892–899.vß1 and vß5. J Biol Chem 1995; 270:26232–26238.4ß1 integrin. J Cell Sci 1998; 111:1165–1174.[Abstract]vß3 by osteopontin stimulates phosphatidylinositol 3-hydroxy kinase activity. Endocrinology 1995; 136:2984–2992.[Abstract]) alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes. J Mol Endocrinol 1995; 15:203–220.vß3 integrin ligands increase intracellular [Ca++] in rat osteoclasts and mouse derived osteoclast-like cells. Am J Physiol 1994; 266:C367–381.This article has been cited by other articles:
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  A. Banerjee, R. Rose, G. A. Johnson, R. C. Burghardt, and S. K. Ramaiah The Influence of Estrogen on Hepatobiliary Osteopontin (SPP1) Expression in a Female Rodent Model of Alcoholic Steatohepatitis Toxicol Pathol, June 1, 2009; 37(4): 492 - 501. [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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R. C Burghardt, J. R Burghardt, J. D Taylor II, A. T Reeder, B. T Nguen, T. E Spencer, K. J Bayless, and G. A Johnson Enhanced focal adhesion assembly reflects increased mechanosensation and mechanotransduction at maternal-conceptus interface and uterine wall during ovine pregnancy Reproduction, March 1, 2009; 137(3): 567 - 582. [Abstract] [Full Text] [PDF]
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 G. Song, K. A. Dunlap, J. Kim, D. W. Bailey, T. E. Spencer, R. C. Burghardt, G. F. Wagner, G. A. Johnson, and F. W. Bazer Stanniocalcin 1 Is a Luminal Epithelial Marker for Implantation in Pigs Regulated by Progesterone and Estradiol Endocrinology, February 1, 2009; 150(2): 936 - 945. [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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G. Song, T. E. Spencer, and F. W. Bazer Progesterone and Interferon-{tau} Regulate Cystatin C in the Endometrium Endocrinology, July 1, 2006; 147(7): 3478 - 3483. [Abstract] [Full Text] [PDF]
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G. Song, F. W. Bazer, G. F. Wagner, and T. E. Spencer Stanniocalcin (STC) in the Endometrial Glands of the Ovine Uterus: Regulation by Progesterone and Placental Hormones Biol Reprod, May 1, 2006; 74(5): 913 - 922. [Abstract] [Full Text] [PDF]
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F. J. White, J. W. Ross, M. M. Joyce, R. D. Geisert, R. C. Burghardt, and G. A. Johnson Steroid Regulation of Cell Specific Secreted Phosphoprotein 1 (Osteopontin) Expression in the Pregnant Porcine Uterus Biol Reprod, December 1, 2005; 73(6): 1294 - 1301. [Abstract] [Full Text] [PDF]
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G. Song, T. E. Spencer, and F. W. Bazer Cathepsins in the Ovine Uterus: Regulation by Pregnancy, Progesterone, and Interferon Tau Endocrinology, November 1, 2005; 146(11): 4825 - 4833. [Abstract] [Full Text] [PDF]
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T. E Spencer, G. A Johnson, F. W Bazer, and R. C Burghardt Implantation mechanisms: insights from the sheep Reproduction, December 1, 2004; 128(6): 657 - 668. [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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 C. A. Gray, D. L. Adelson, F. W. Bazer, R. C. Burghardt, E. N. T. Meeusen, and T. E. Spencer Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm PNAS, May 25, 2004; 101(21): 7982 - 7987. [Abstract] [Full Text] [PDF]
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G. A. Johnson, R. C. Burghardt, F. W. Bazer, and T. E. Spencer Osteopontin: Roles in Implantation and Placentation Biol Reprod, November 1, 2003; 69(5): 1458 - 1471. [Abstract] [Full Text] [PDF]
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G. A. Johnson, R. C. Burghardt, M. M. Joyce, T. E. Spencer, F. W. Bazer, C. A. Gray, and C. Pfarrer Osteopontin Is Synthesized by Uterine Glands and a 45-kDa Cleavage Fragment Is Localized at the Uterine-Placental Interface Throughout Ovine Pregnancy Biol Reprod, July 1, 2003; 69(1): 92 - 98. [Abstract] [Full Text] [PDF]
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G. A. Johnson, R. C. Burghardt, M. M. Joyce, T. E. Spencer, F. W. Bazer, C. Pfarrer, and C. A. Gray Osteopontin Expression in Uterine Stroma Indicates a Decidualization-Like Differentiation During Ovine Pregnancy Biol Reprod, June 1, 2003; 68(6): 1951 - 1958. [Abstract] [Full Text] [PDF]
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K.B.C. Apparao, M. J. Illera, S. A. Beyler, G. E. Olson, K. G. Osteen, M. H. Corjay, K. Boggess, and B. A. Lessey Regulated Expression of Osteopontin in the Peri-Implantation Rabbit Uterus Biol Reprod, May 1, 2003; 68(5): 1484 - 1490. [Abstract] [Full Text] [PDF]
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 J. M. Borthwick, D. S. Charnock-Jones, B. D. Tom, M. L. Hull, R. Teirney, S. C. Phillips, and S. K. Smith Determination of the transcript profile of human endometrium Mol. Hum. Reprod., January 1, 2003; 9(1): 19 - 33. [Abstract] [Full Text] [PDF]
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J. E. Garlow, H. Ka, G. A. Johnson, R. C. Burghardt, L. A. Jaeger, and F. W. Bazer Analysis of Osteopontin at the Maternal-Placental Interface in Pigs Biol Reprod, March 1, 2002; 66(3): 718 - 725. [Abstract] [Full Text] [PDF]
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 K. B. C. Apparao, M. J. Murray, M. A. Fritz, W. R. Meyer, A. F. Chambers, P. R. Truong, and B. A. Lessey Osteopontin and Its Receptor {alpha}v{beta}3 Integrin Are Coexpressed in the Human Endometrium during the Menstrual Cycle But Regulated Differentially J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4991 - 5000. [Abstract] [Full Text] [PDF]
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G. A. Johnson, F. W. Bazer, L. A. Jaeger, H. Ka, J. E. Garlow, C. Pfarrer, T. E. Spencer, and R. C. Burghardt Muc-1, Integrin, and Osteopontin Expression During the Implantation Cascade in Sheep Biol Reprod, September 1, 2001; 65(3): 820 - 828. [Abstract] [Full Text] [PDF]
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E. Asselin, G. A. Johnson, T. E. Spencer, and F. W. Bazer Monocyte Chemotactic Protein-1 and -2 Messenger Ribonucleic Acids in the Ovine Uterus: Regulation by Pregnancy, Progesterone, and Interferon-{{tau}} Biol Reprod, March 1, 2001; 64(3): 992 - 1000. [Abstract] [Full Text]
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