Arachidonic acid in uterine phospholipid during early pregnancy and following hormone treatment

Evidence that prostaglandins are involved in intercellular communication during blastocyst implantation suggested that development and loss of uterine sensitivity to deciduogenic stimuli during early pregnancy might depend upon changes in uterine capacity to mobilize arachidonic acid from phospholipid. We measured levels of arachidonic acid in lipid fractions on Day 6 of pregnancy in uterine segments containing implantation sites, in uterine segments between implantation sites, and in luminal epithelial cells after a deciduogenic stimulus. Arachidonic acid in uterine phospholipid was depleted at implantation sites. With an intrauterine deciduogenic stimulus of hormonally primed ovariectomized rat uteri, the arachidonic acid content of the luminal epithelium decreased. When the fatty acid composition of the luminal epithelium was examined during pseudopregnancy and after progestin-estrogen treatment, however, no changes in arachidonic acid composition and content were observed. These data suggest that during blastocyst implantation, luminal epithelial cells at implantation sites mobilize arachidonic acid from phospholipid for prostaglandin synthesis, but that uterine sensitivity and the capacity to synthesize prostaglandins in response to the blastocyst does not depend upon changes in arachidonic acid levels in uterine phospholipid.     

Uterine luminal proteins and estrogens in gilts on a normal nutritional plane during the estrous cycle and on a normal or high nutritional plane during early pregnancy

In gilts, a high plane of nutrition during early pregnancy often results in increased embryo mortality, possibly related to changes in embryo-uterine asynchrony at a critical stage of pregnancy (around Day 11). Therefore, in the present study, uterine luminal proteins and estrogens were studied between Days 5 and 16 after the onset of estrus in gilts on either a normal (2.5 kg/d, cyclic and pregnant gilts) or a high (4.0 kg/d, pregnant gilts only) feeding level. Conceptus recovery rate between Days 5 and 12 was not affected by the feeding level during early pregnancy, neither were systemic progesterone levels. Between Days 9 and 11, dramatic changes took place in the protein composition of the uterine luminal 10kD+ proteins, shifting from most (90%) of the acidic proteins at Day 5 and 7 to approximately 50% at Day 11/12, especially due to an increase in basic proteins with an iso-electrical point of more than 8. This shift occurred most rapidly for the pregnant gilts at the high feeding level and least rapidly in the cyclic gilts, resulting in significant differences in the relative amount of acidic proteins at Day 10 and 11 after the onset of estrus (P < 0.05). Similarly, levels of estrogens in the uterine flushings at Days 10, 11 and 12 were always highest for the pregnant gilts on the high feeding level and were always lowest in the cyclic gilts (P < 0.05); pregnant gilts on the normal feeding level showed intermediate estrogen levels. The fact that gilts on a high feeding level during early pregnancy show more rapid changes in the uterine luminal protein composition and embryonic estrogen production seems to suggest that the rate of these changes may be related to embryo survival.     

Stage-specific expression of the intermediate filament protein cytokeratin 13 in luminal epithelial cells of secretory phase human endometrium and peri-implantation stage rabbit endometrium

In preparation for blastocyst implantation, uterine luminal epithelial cells express new cell adhesion molecules on their apical plasma membrane. Since one mechanism epithelial cells employ to regulate membrane polarity is the establishment of specific membrane-cytoskeletal interactions, this study was undertaken to determine if new cytokeratin (CK) intermediate filament assemblies are expressed in endometrial epithelial cells during developmental stages related to blastocyst implantation. Type-specific CK antibodies were used for immunocytochemical and immunoblot analyses of 1) intermediate filament networks of the endometrial epithelium during embryo implantation in rabbits and 2) proliferative and secretory phases of the human menstrual cycle. CK18, a type I CK found in most simple epithelia, was expressed in all luminal and glandular epithelial cells of both the human and rabbit endometrium at all developmental stages analyzed; it was also strongly expressed in trophectoderm of the implanting rabbit blastocyst. In contrast, CK13, another type I cytokeratin, exhibited a regulated expression pattern in luminal, but not glandular, epithelial cells of secretory phase human and peri-implantation stage rabbit endometrium. Furthermore, in the rabbit implantation chambers, CK13 was predominantly localized at the cell apex of luminal epithelial cells, where it assembled into a dense filamentous network. These data suggest that the stage-specific expression of CK13 and a reorganization of the apical intermediate filament cytoskeleton of uterine luminal epithelial cells may play important functions in preparation for the implantation process.     

Ovine osteopontin: II. Osteopontin and alpha(v)beta(3) integrin expression in the uterus and conceptus during the periimplantation period.

Osteopontin (OPN) is an acidic 70-kDa glycoprotein that is cleaved by proteases to yield 45-kDa and 24-kDa fragments. The 70-kDa and 45-kDa proteins contain a Gly-Arg-Gly-Asp-Ser (GRGDS) sequence that binds to cell surface integrins (primarily alpha(v)beta(3) heterodimer) to promote cell-cell attachment and cell spreading. A 70-kDa acidic protein was previously detected by two-dimensional (2D) PAGE in Day 17 pregnant endometrial cytosolic extracts using Stainsall and identified as immunoreactive OPN using Western blotting. Three forms of immunoreactive OPN proteins (70, 45, and 24 kDa) were detected by 1D PAGE and Western blot analysis of endometrial extracts. OPN protein in endometrial extracts did not differ between cyclic and pregnant ewes. However, the amount of 45-kDa OPN increased in uterine flushings from pregnant ewes between Days 11 and 17. Immunoreactive OPN was localized to luminal and glandular epithelia of both cyclic and pregnant ewes, and to trophectoderm of Day 19 conceptuses. The alpha(v) and beta(3) integrins were detected on Day 19 endometrium and conceptuses by immunofluorescence. It was reported that OPN mRNA increases in the uterine glands of pregnant ewes and secretion of OPN protein into the uterine lumen increases during early pregnancy. The present results demonstrate accumulation of OPN protein on endometrial LE and conceptus trophectoderm. Therefore, it is hypothesized that progesterone and/or interferon-tau induce expression, secretion and/or proteolytic cleavage of OPN by uterine epithelium. Secreted OPN is then available as ligand for alpha(v)beta(3) integrin heterodimer on trophectoderm and uterus to 1) stimulate changes in morphology of conceptus trophectoderm and 2) induce adhesion between luminal epithelium and trophectoderm essential for implantation and placentation.     

Cell-type-specific expression of transforming growth factor-alpha in the mouse uterus during the peri-implantation period.

Immunohistochemistry as well as in situ and Northern blot hybridization were employed to determine temporal and cell-type-specific expression of transforming growth factor-alpha (TGF-alpha) in the mouse uterus during the peri-implantation period. The co-localization of TGF-alpha (by immunohistochemistry) with its mRNA (by in situ hybridization) in the luminal and glandular epithelia on Days 1-4 of pregnancy (Day 1 = vaginal plug) and also in many stromal cells on Days 3 and 4 indicates that these cells are the primary sites of TGF-alpha synthesis during the preimplantation period. The higher levels of TGF-alpha mRNA in total uterine RNA on Day 4, as shown by Northern blotting, is consistent with the recruitment of stromal cells expressing this gene. During the post-implantation period (Days 5-8), the co-localization of the mRNA and protein in the decidua at the implantation sites suggests that the decidualizing stromal cells synthesize TGF-alpha. Although in situ hybridization showed the presence of mRNA in embryos on Days 5-8, immunostaining was noted in the embryo only on Days 5 and 6. These results suggest that uterine and embryonic expression of TGF-alpha during the peri-implantation period could be involved in embryonic development, preparation of the uterus for implantation, and decidualization.     

Mating modifies apoptosis pattern in epithelial cells of the rat uterus

Estrous cycle in mammals includes marked epithelial changes in reproductive tract, regulated by sex steroid hormones. In the present work we studied the activation of caspases and apoptotic pattern in uterine epithelial cells during proestrus and estrus, and the effect of mating in this process. In addition, we investigated the role of seminal vesicle secretions on apoptosis of uterine epithelia. Apoptotic index was evaluated by TUNEL assay, caspases‐8, ‐9, and ‐3 activation was detected by Western blot and active caspase‐3 expression was detected by immunohistochemistry. Our results show that mating during proestrus and estrus transition induced changes in the apoptotic pattern of uterine luminal epithelium during estrus, characterized by a delay in the onset of apoptosis as compared with that observed in nonmated rats. No differences in the apoptotic pattern in the glandular epithelium between mated and nonmated rats were observed. Seminal vesicle secretions inhibited luminal epithelium apoptosis, while no changes in glandular epithelium apoptosis were observed. We also demonstrate that activation of caspases‐8, ‐9, and ‐3 occurred in both mated and nonmated rats. Active caspase‐3 was detected in the luminal and glandular epithelium in both nonmated and mated rats. The overall results indicate that mating delays but does not prevent the cellular death of the rat uterine luminal epithelium and seminal vesicle secretions are involved in this delay. Finally, the activation of both the mitochondrial and the membrane receptor pathways of cell death are implicated in the molecular mechanism of uterine apoptosis. Mol. Reprod. Dev. 76: 564–572, 2009. © 2008 Wiley‐Liss, Inc.     

Epithelial cell function during blastocyst implantation

In response to the ovarian secretion of progesterone and estrogen during early pregnancy, the mammalian uterus develops the capacity to perform complex cellular activities which occur before and after blastocyst implantation. Luminal epithelial cells participate in regulation of the metabolism of the blastocyst through the control of its humoral environment, provide an appropriate matrix for changes to occur at the interface between trophoblast and epithelium, and appear to transmit information from the blastocyst to the underlying stroma to initiate decidualization. With the completion of these functions during implantation in rodents, the epithelial cells self-destruct and are removed by phagocytic activity of the trophoblast. Control of both the endocytotic and secretory activity of luminal epithelial cells and their eventual self-destruction would require regulation of the Golgi-endoplasmic reticulum-lysosomes system within these cells. Progesterone secretion during early pseudo-pregnancy increases levels of cathepsin D, a lysosomal proteinase, in luminal epithelial cells by increasing the rate of enzyme synthesis. Progesterone pretreatment of ovariectomized rats followed by estradiol treatment results in the development of uterine sensitivity to deciduogenic stimuli. The number of proteins which are synthesized by luminal epithelial cells in response to estradiol to achieve this sensitivity has been determined. Epithelial cytosol proteins from rats treated with medroxyprogesterone acetate (3.5 mg sc) or medroxyprogesterone acetate plus estradiol (200 ng sc) were separated by two dimensional polyacrylamide gel electrophoresis. The synthesis of two proteins increased after 8 h of estradiol treatment and the synthesis of another three was increased by 12 h. The increased synthesis of these proteins could be related to changes in the capacity of the luminal epithelial cell for prostaglandin synthesis. The epithelial capacity for prostaglandin synthesis increases during pseudopregnancy to maximum levels at the time of maximum sensitivity to deciduogenic stimuli. Epithelial prostaglandin synthetic capacity may also depend upon the accumulation of prostaglandin precursors within these cells. Estradiol treatment of medroxyprogesterone acetate pretreated ovariectomized rats increased the arachidonic acid content and composition of epithelial phosphatidyl choline but the increases were not statistically significant. These changes in protein and lipid synthesis controlled by progesterone and estrogen would appear to contribute to the cellular activities of the luminal epithelium during early pregnancy.     

Role of prostaglandins in development of porcine blastocysts

Rapid elongation of porcine blastocysts between Days 11 to 12 of pregnancy coincides with an increase in uterine luminal content of prostaglandins. The present study evaluated the effect of two prostaglandin synthesis inhibitors (indomethacin and flunixin meglumine) on elongation of porcine blastocysts from spherical to filamentous forms between Day 11 to 12 of pregnancy. Gilts were hemi-hysterectomized on Day 11 of pregnancy. The excised uterine horn was flushed with 0.9% saline and diameter of blastocysts recovered were measured. Immediately following surgery, pregnant gilts were assigned to receive either: 1) vehicle every 4 h, 2) flunixin meglumine (banamine) every 4 h, or 3) indomethacin every 12 h. The remaining uterine horn was removed and flushed after the time of blastocyst elongation estimated for each gilt on basis of blastocyst development in the first horn. Uterine flushings were analyzed for total calcium, protein, acid phosphatase activity, estrone, estradiol-17 beta and prostaglandin F. Pretreatment blastocyst diameter was similar for all groups and ranged from 1 mm to 20 mm. Treatment of gilts with either banamine or indomethacin effectively inhibited (P less than 0.001) the increase in uterine luminal content of PGF. Total calcium, estrone and estradiol-17 beta were not influenced by treatment. Total uterine luminal protein and acid phosphatase activity were reduced (P less than 0.05) in banamine treated gilts compared to those receiving vehicle or indomethacin treatments. Although total PGF recovered in uterine flushings was reduced during the period of blastocyst elongation, treatment with PGF synthetase inhibitors failed to block rapid elongation of blastocysts from the spherical to filamentous forms.     

Expression of p53 in luminal and glandular epithelium during the growth and regression of rat uterus during the estrous cycle

It has been well recognized that epithelial cells of the rat endometrium cyclically proliferate and die during the estrous cycle. The aim of the present study was to determine p53 expression pattern and correlate it with the the apoptotic pattern of epithelial cells of the rat uterus during the estrous cycle. The p53 mRNA and protein expression pattern was assessed by in situ hybridization and immunohistochemistry. The apoptotic index was determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and electron microscopy. The highest p53 mRNA content, detected by in situ hybridization, was observed on the metestrus day both in the luminal and the glandular epithelia. During this period both epithelia presented high proliferation. The content of p53 mRNA markedly decreased in the following days, presenting its minimal values on the estrus day. The highest number of p53 immunopositive nuclei, in both the luminal and the glandular epithelia, was also detected on the metestrus day, while the lowest one was found on estrus day. On the proestrus day, p53 protein was predominantly detected in the glandular epithelium. However, on the estrus day, p53 protein was detected both in the nuclei and in the cytoplasm of luminal epithelial cells, predominantly in the cytoplasm. The highest apoptotic index in both the luminal and the glandular epithelia was observed on the estrus day whereas the lowest one was observed on the proestrus day. The apoptotic index values were higher in the luminal than in the glandular epithelia. The overall results indicate that p53 expression at both mRNA and protein levels is higher on the metestrus day when the apoptotic index is low. This suggests that p53 should play an important physiological role during proliferative phases of the estrous cycle in the rat uterus.     

Expression of tenascin-C in stromal cells of the murine uterus during early pregnancy: induction by interleukin-1 alpha, prostaglandin E(2), and prostaglandin F(2 alpha)

Tenascin-C (TN-C), an extracellular matrix glycoprotein, is known to be expressed in uterine stroma in the peri-implantation period. Examination of the spatiotemporal pattern during early pregnancy using immunohistochemistry and in situ hybridization revealed TN-C expression in the stroma beneath the luminal epithelia of the murine endometrium on Days 0 and 1 of pregnancy, subsequent disappearance, and reappearance on Day 4. After decidualization, tissue around the deciduoma was positive. In situ hybridization demonstrated TN-C production by the stromal cells adjacent to the epithelia. To investigate the regulation of TN-C expression in vitro, murine uterine stromal and epithelial cells were isolated and cultured. Addition of interleukin-1 alpha (IL-1 alpha) and prostaglandin E(2) (PGE(2)) and F(2 alpha) (PGF(2 alpha)) induced TN-C expression in the stromal cells at both protein and mRNA levels, while the sex steroid hormones, progesterone and ss-estradiol, exerted little effect. Immunohistochemistry using anti-IL-1 alpha antibody showed epithelial cells to be positive on Days 2-4 of pregnancy, and addition of progesterone but not ss-estradiol enhanced IL-1 alpha expression in epithelial cells in vitro. In a culture insert system, TN-C expression by stromal cells cocultured with epithelial cells was induced by addition of progesterone alone that was blocked by additions of anti-IL-1 alpha antibody. Collectively, these findings indicate that TN-C expression in the preimplantation period is under the control of progesterone, but not directly, possibly by the paracrine and autocrine intervention of IL-1 alpha secreted by epithelial cells and PGE(2) and PGF(2 alpha) secreted by stromal cells.     

Immunohistochemical investigation of secretory component and immunoglobulin A in the genital tract of the female rat

There was intense labelling of secretory component (sc) in the glandular and luminal epithelia of the uterine horns at pro-oestrus, oestrus and Day 1 of pregnancy, but at other stages labelling was weak or undetectable. There was also intense labelling of sc in the superficial layer of cells in the stratified epithelia of the cervix and vagina at pro-oestrus and Days 4-7 of pregnancy, but not at other stages. Plasma cells containing immunoglobulin A (IgA) were not observed in any region of the genital tract at any of the times studied. The presence of sc coupled with an absence of IgA-containing plasma cells suggest that IgA in genital tract secretions of the female rat may be derived mainly from serum.     

Expression and hormonal regulation of calcyclin-binding protein (CacyBP) in the mouse uterus during early pregnancy

Calcyclin-binding protein (Siah-1-Interacting Protein, CacyBP/SIP), is a calcium signaling protein involved in the degradation of beta-catenin, however, little is known about its role in reproductive biology. The present study was to character its temporospatial expression pattern and regulation in mouse uterus and to investigate whether it plays a role in the regulation of normal endometrial events. While prominently expressed in both luminal and glandular epithelia, CacyBP underwent dynamic changes during early pregnancy. CacyBP expression was observed weakly from days 1-4. An intense accumulation in luminal and glandular epithelia as well as decidua surrounding the embryo at later stages (days 5-7) was observed. Most notably, CacyBP accumulation in trophoblast was pronounced at day 7. Using ovariectomized and pseudopregnant mice, we found that progesterone (P(4)) and 17beta-estradiol (E(2)) led to increased expression of CacyBP gene and this could be abolished by Ru486 and tamoxifen, respectively. Antisense oligonucleotides (ODNs) against CacyBP significantly inhibited cultured endometrial stromal cells' (ESCs) apoptosis induced by UV irradiation. Injection of antisense ODNs into mouse uterine horn severely impaired the number of implanted blastocysts. Taken together, our results suggested that CacyBP expression was positively regulated by P(4) and E(2). CacyBP may be involved in the regulation of endometrial cell apoptosis during early pregnancy and play an important role in mouse endometrial events such as pregrancy establishment.     

Estradiol receptor binding to the epithelium of uterine lumen and glands: region- and time-related changes during preimplantation and periimplantation periods studied by autoradiography

The presence and changes of estradiol nuclear binding and related functions in uterine luminal and glandular epithelium were studied before and after blastocyst implantation using receptor autoradiography with ³H-estradiol-17 in association with ³H-thymidine incorporation and immunocytochemical binding of antibody to estrogen receptor ER-. ³H-estradiol nuclear binding is present but variable during days 1.5–7.5 of pregnancy. Sites of strong nuclear binding of ³H-estradiol exhibit strong immunocytochemical staining with ER- antibody. Qualitative and quantitative evaluation of autoradiograms reveal that there is a general increase of nuclear ³H-estradiol binding during the first 3 days after fertilization in both luminal and glandular epithelium. The binding of estradiol is stronger in glandular epithelium from day 2.5 to day 7.5, paralleled by a rise in ³H-thymidine incorporation on day 2.5. By comparison, in the epithelium of the uterine lumen ³H-estradiol nuclear binding is low, but relatively high in epithelial cells at lateral branching of the lumen where the increase in ³H-estradiol binding corresponds to an increased labeling index with ³H-thymidine. A highly differentiated binding of ³H-estradiol to luminal and glandular epithelium was demonstrated with region- and time-specific changes of related effects on cell proliferation, differentiation, and secretion, probably involving involution and remodeling. The strong ³H-estradiol binding to glandular epithelium suggests that estradiol exerts pronounced effects on glandular activities in the periimplantation period.     

Apoptosis in endometrium of mouse during estrous cycle

The present study was carried out to evaluate apoptosis in endometrium and to correlate these changes with the circulating levels of estradiol and progesterone in the mouse. Apoptosis was observed in various compartments of mouse uterus i.e. stroma, glandular epithelium and luminal epithelium depending on the stage of cycle. Stromal cell apoptosis was observed during various stages of cyclicity except on estrus day. Luminal epithelial cells showed apoptotic changes during all stages of cyclicity except on diestrus day. During metestrus, apoptosis was observed in glandular and luminal epithelia as well as stromal cells. Steroid antagonists such as tamoxifen and onapristone altered the apoptotic changes in the uterus. The results suggest that epithelial cell apoptosis is regulated by estrogen while stromal cell apoptosis is under the control of progesterone.     

Immunofluorescent localization, by use of anti-idiotypic antibody, of monoclonal anti-progesterone antibody in the mouse uterus before implantation

Mouse monoclonal anti-progesterone IgG1 antibody designated DB3 has an anti-fertility effect when injected into female mice shortly after mating. In BALB/c mice, pregnancy is blocked, probably as a result of progesterone withdrawal with inhibition of implantation. Rabbit polyclonal anti-idiotype raised against DB3 has been used in an indirect immunofluorescence method on frozen tissue sections to demonstrate the presence of DB3 on the surface of uterine luminal and glandular epithelia before implantation. DB3 was only detectable 30-60 h after a single parenteral injection (9 nmol antibody per mouse i.p. or i.v. at 32 h post coitum). Immunolocalization was both pregnancy-dependent and anti-progesterone antibody-specific, as it was not seen in pseudopregnant mice or mice treated with P3 (mouse myeloma IgG1 protein, using polyclonal anti-P3 anti-idiotype as a probe) or saline. The immunofluorescent reaction was completely blocked by addition of DB3 idiotype in vitro. The results indicate that anti-progesterone antibody binds to an antigen associated with luminal and glandular epithelia which may locally inhibit the uterine uptake of progesterone and disrupt the process of implantation.     

Immunohistochemical demonstration of cyclooxygenase-2 (COX-2) and prostaglandin receptors EP2 and FP expression in the bovine intercaruncular uterine wall around term

During parturition, uterine-derived prostaglandins (PG) play an outstanding role regarding the functional elimination of the corpus luteum and the promotion of uterine contraction. The rate-limiting enzyme cyclooxygenase-2 (COX-2), highly regulated in a cell-type and localization specific manner throughout pregnancy, is involved in uterine prostanoid production. Prostaglandins exert their effects via G-protein-coupled receptors. Distribution and cellular localization of these receptors are decisive factors for prostaglandin-mediated actions. Since both COX-2 and PG receptors have only been assessed during pregnancy in the cow, these parameters were localized immunohistochemically near term to evaluate their specific role at parturition. Thus, during two periods, segments of the intercaruncular uterine wall were collected from cows at slaughter being eight and nine months pregnant, from cattle during caesarean section, and after spontaneous calving.

Results reveal that COX-2 was mainly localized in the cytoplasm of surface epithelial cells with a high expression in animals with induced parturition. The enzyme could also be found in lower concentrations within the glandular epithelium without any effect of gestational time or labour. In contrast to relaxant prostaglandin E receptor type 2 (EP2), not showing any change in all tissue layers observed, contractile prostaglandin F₂ receptor (FP) was modulated during the peripartal period revealing a peak expression in animals with induced parturition. FP was localized in surface and glandular epithelial cells as well as in endometrial stroma and myometrial smooth muscle cells.

Our study indicates that labour and induction of parturition may have an effect on amounts of immunohistochemically detectable COX-2 and FP. EP2 remains rather unchanged during the peripartal period. COX-2 and FP thus contribute via changes in amount and distribution to mechanisms associated with parturition.     

Select nutrients in the ovine uterine lumen. ii. glucose transporters in the uterus and peri-implantation conceptuses

Total glucose in ovine uterine lumenal fluid increases 6-fold between Days 10 and 15 of gestation, but not the estrous cycle; however, mechanisms for glucose transport into the uterine lumen and uptake by conceptuses (embryo/fetus and associated membranes) are not established. This study determined the effects of the estrous cycle, pregnancy, progesterone (P4), and interferon tau (IFNT) on expression of both facilitative (SLC2A1, SLC2A3, and SLC2A4) and sodium-dependent (SLC5A1 and SLC5A11) glucose transporters in ovine uterine endometria from Days 10 to 16 of the estrous cycle and Days 10 to 20 of pregnancy, as well as in conceptuses from Days 10 to 20 of pregnancy. The SLC2A1 and SLC5A1 mRNAs and proteins were most abundant in uterine luminal epithelia and superficial glandular epithelia (LE/sGE), whereas SLC2A4 was present in stromal cells and glandular epithelia (GE). SLC5A11 mRNA was most abundant in endometrial GE, whereas SLC2A3 mRNA was not detectable in endometria. SLC2A1, SLC2A3, SLC2A4, SLC5A1, and SLC5A11 were expressed in the trophectoderm and endoderm of conceptuses. Steady-state levels of SLC2A1, SLC5A1, and SLC5A11 mRNAs, but not SLC2A4 mRNA, were greater in endometria from pregnant than from cyclic ewes. Progesterone increased SLC2A1, SLC5A11, and SLC2A4 mRNAs in the LE/sGE and SLC5A1 in the GE of ovariectomized ewes. Expression of SLC5A1 was inhibited by ZK136,317 (progesterone receptor antagonist), and the combination of ZK136,317 and IFNT further decreased expression in GE. In constrast, P4 induced and IFNT stimulated expression of SLC2A1 and SLC5A11, and these effects were blocked by ZK136,317. Results of this study indicate differential expression of facilitative and sodium-dependent glucose transporters in ovine uteri and conceptuses for transport and uptake of glucose, and that P4 or P4 and IFNT regulate their expression during the peri-implantation period of pregnancy.