Prostaglandins and parturition.
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Animals↗
Biomedical subjects
S J Lye
Publications and source records attributed to S J Lye.
Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants.
Successful invasion of the maternal vascular system by trophoblast cells is a prerequisite for the establishment of a normal hemochorial placenta. Transforming growth factor-beta (TGFbeta) has been implicated in the regulation of trophoblast invasiveness into the uterus. Endoglin is a component of the TGFbeta receptor complex that binds beta1 and beta3 isoforms and is expressed at high levels on syncytiotrophoblast throughout pregnancy and is also transiently up-regulated on extravillous trophoblasts differentiating along the invasive pathway. We investigated the role of endoglin in a serum-free human villous explant culture system that allows the study of trophoblast outgrowth, migration, and invasion and mimics events occurring in anchoring villi during the first trimester of gestation. Addition to explant cultures from 5-8 weeks gestation of a monoclonal antibody to endoglin or of antisense endoglin oligonucleotides significantly stimulated trophoblast outgrowth and migration. These responses were specific, as incubation of explants with nonimmune IgG or sense and scrambled oligonucleotides had no effect. Antisense endoglin-induced trophoblast outgrowth and migration were accompanied by cell division of villous-associated trophoblasts within the proximal region of the forming column and by the characteristic switch in integrins observed in anchoring villi in situ. Treatment of villous explants with antibody and antisense oligonucleotides to endoglin also resulted in an increased fibronectin release into the culture medium. The stimulatory effect of antisense endoglin on fibronectin production was overcome by the addition of exogenous TGFbeta2, but not TGFbeta1 and -beta3. These findings suggest that endoglin expression in the transition from polarized to nonpolarized trophoblasts in anchoring villi is necessary for mediation of the inhibitory effect of TGFbeta1 and/or TGFbeta3 on trophoblast differentiation along the invasive pathway.
Antibodies↗
Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals.
We investigated the effects of uterine stretch on the levels of messenger RNA (mRNA) encoding the gap junction proteins connexin-43 (Cx-43) and connexin-26 (Cx-26) as well as the presence of gap junction plaques formed by Cx-43 within the myometrium. In nonpregnant ovariectomized rats, stretch of one uterine horn with a polyvinyl tube induced a significant increase in myometrial Cx-43 mRNA levels, an effect that was blocked by progesterone; no expression of Cx-26 was detected in the presence or absence of stretch. To investigate whether pregnancy and parturition modified the response to stretch, unilaterally pregnant rats underwent either sham operation or placement of a tube in the nongravid uterine horns. On day 20 of pregnancy, expression of Cx-43 mRNA in gravid horns was low, and stretch did not increase this level. Cx-26 mRNA expression was elevated at this time, but only in the gravid horns. Cx-43 mRNA was highly expressed in the myometrium of gravid horns during labor, but Cx-43 expression in sham-operated, nongravid horns remained low. In contrast, nongravid horns stretched with tubes expressed Cx-43 mRNA at levels similar to those in gravid horns. Levels of Cx-26 mRNA in gravid horns fell between days 20 and 23, and this was not altered by stretch. Punctate Cx-43 immunofluorescence (indicative of gap junction formation) also increased in the myometrium after uterine stretch and in gravid horns during labor. Our data demonstrate that differential mechanisms regulate the expression of Cx-43 and Cx-26 in the pregnant myometrium. Cx-43 expression during labor is dependent upon myometrial stretch under conditions of low progesterone. In contrast, Cx-26 expression during late pregnancy, although requiring the presence of the fetal/placental unit, does not require stretch of the myometrium.
Animals↗
Activin is a local regulator of human cytotrophoblast cell differentiation.
Cytotrophoblast cells of the first trimester placenta are highly invasive when removed from villi and cultured in vitro. In vivo, however, only selected cytotrophoblast cells break through the overlying syncytiotrophoblast to form cytotrophoblast columns and ultimately invade the endometrium. To explore the role of paracrine growth factors in regulating cytotrophoblast development, we cultured explants of first trimester chorionic villi in vitro. Both activin and inhibin, as well as the activin binding protein follistatin, are produced by various trophoblast cells throughout pregnancy. We found that addition of activin-A, but not inhibin-A, stimulated the outgrowth of cytotrophoblast cells into the surrounding matrix. This outgrowth was characteristic of that observed in extravillous cytotrophoblast cells in vivo; it was accompanied by cell division within the proximal region of the cytotrophoblast outgrowth, synthesis of fibronectin, as well as the expression of markers characteristic of invasive cytotrophoblast cells, human leukocyte antigen-G and matrix metalloproteinase (MMP)-9. Activin also specifically induced the early expression of MMP-2 within villous cytotrophoblast cells. Addition of the activin binding protein, follistatin, blocked all of the effects of exogenous activin. The morphological and biochemical effects of activin were similar to those observed when signaling of endogenous transforming growth factor-beta was blocked. Interestingly, the latter effects were also reversed by the addition of follistatin. These data suggest that activin plays a local role in promoting cytotrophoblast column formation, likely by regulating the differentiation of villous cytotrophoblast into extravillous cytotrophoblast cells.
Activins↗
The expression of integrins and cadherins in normal human uterus and uterine leiomyomas.
OBJECTIVES: Our purpose was to examine the pattern of integrin and cadherin expression in the normal human uterus and uterine leiomyomas. STUDY DESIGN: Nonpathologic myometrium and endometrium and uterine leiomyoma tissues were collected during hysterectomy. The pattern of integrin and cadherin expression displayed by these tissues was assessed by use of immunohistochemical staining. A transformed leiomyoma cell line was assessed for expression of integrins and cadherins with flow cytometry. RESULTS: The human myometrium was found to express numerous integrins and cadherins in a cell-specific manner, differing among smooth muscle cells, stromal cells, and endothelial cells. An identical pattern was seen in uterine leiomyomas. In contrast to the endometrium, expression of integrins and cadherins in the myometrium remained constant throughout the menstrual cycle. CONCLUSIONS: This article characterizes the expression of integrins and cadherins in the human uterus. In contrast to many tumors, the growth and development of leiomyomas are not associated with a fundamental change in expression of these cell adhesion molecules. The mechanisms regulating expression of integrins in myometrium and endometrium must be different.
Adult↗
Rat uterine myometrium contains the gap junction protein connexin45, which has a differing temporal expression pattern from connexin43.
OBJECTIVE: Our purpose was to determine whether myometrial cell lines and rat myometrial tissue contained additional gap junction proteins besides connexin43. STUDY DESIGNS: Syrian hamster myocytes (SHM-ER) and human SK-UT-1 myometrial cell lines were analyzed for intercellular coupling by microinjection of Lucifer yellow. These cell lines and myometrial tissue isolated from pregnant rats were analyzed for connexin expression by ribonucleic acid blotting and immunofluorescence. RESULTS: SHM-ER and SK-UT-1 cells showed functional gap junctional coupling by intercellular passage of microinjected dye. Both cell lines contained connexin43 and connexin45 messenger ribonucleic acids but did not contain any other detectable connexin messenger ribonucleic acids. Immunofluorescence confirmed the presence of connexin43 and connexin45 proteins in these cells. Connexin 43 and connexin45 messenger ribonucleic acids and immunoreactive proteins were detected in pregnant rat myometrium. Connexin 43 messenger ribonucleic acid levels increased dramatically at term. In contrast, connexin45 messenger ribonucleic acid was present in nonpregnant myometrium, remained relatively constant early in gestation, fell just before term, and more than doubled post partum. CONCLUSIONS: Rat uterine myometrium contains connexin45 and connexin43. Coexpression of connexin45 with connexin43 in uterine myometrium may regulate gap junctional coupling between these cells. The different temporal expression patterns suggest that connexin45 and connexin43 may have different roles or that the ratio of these connexins may be important in the increased cellular coupling coincident with the onset of labor.
Animals↗
Changes in structure, mechanics, and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen.
Exposure of neonatal rats to > or = 95% O2 for 2 wk, a widely used model of oxidant/antioxidant interactions in neonatal lung injury, results in arrested lung growth without the dysplastic lesions observed in chronic human neonatal lung injury. To determine whether dysplastic lung cell growth would be seen at lesser O2 concentrations, we exposed newborn rats to either 95% O2 for 1 wk followed by 60% O2 for 1 wk, or to 60% O2 for 2 wk. Exposure to 95% O2 for 1 wk profoundly inhibited lung DNA synthesis. Recovery of synthesis did not occur during the 2nd wk in 60% O2, nor were areas of dysplastic growth evident in lung tissue. In contrast, a continuous 2-wk exposure to 60% O2 resulted in a slight increase in lung weight with a significant reduction in lung volume over a range of inflation pressures. Also seen was an overall, but inhomogeneous, reduction in lung cell DNA synthesis. A preliminary analysis of affected cell types suggested that inhibition of DNA synthesis affected endothelial cells more than interstitial cells, whereas DNA synthesis increased in type II pneumocytes. Areas of reduced DNA synthesis were interspersed with patchy areas of parenchymal thickening and active DNA synthesis. These areas of parenchymal thickening, but not other areas, had increased immunoreactive IGF-I and the type I IGF receptor. These data are consistent with a direct effect of O2 on growth factor and growth factor receptor expression in causing dysplastic lung cell growth in chronic neonatal lung injury.
Animals↗
Connexin-26 and connexin-43 are differentially expressed and regulated in the rat myometrium throughout late pregnancy and with the onset of labor.
Gap junctions are characteristically increased in the myometrium during term and preterm delivery and are thought to be essential for the development of labor contractions. The expression of connexin-43 (Cx-43), the major myometrial gap junction protein, is increased during delivery (associated with an increase in the plasma estradiol/progesterone ratio) and after estradiol treatment of ovariectomized nonpregnant rats. However, Cx-43 is only 1 member of at least 16 proteins encoded by this family of gap junction genes. Using a RT-PCR method, we identified the presence of another member of this family, Cx-26, in laboring rat myometrium. The temporal expression pattern of Cx-26 was assessed using Northern and Western analyses. In contrast to Cx-43, whose expression is low throughout the pregnancy but increases immediately before the onset of labor (day 23), the expression of Cx-26 increased on day 17, reached maximal levels between days 19-21, and fell to low levels before the onset of labor. Treatment of pregnant rats with progesterone beginning on day 20 (which blocks both the increase in Cx-43 expression and the onset of labor) maintained the elevated expression of Cx-26. Induction of preterm labor in rats after ovariectomy on day 17 inhibited the normal preterm increase in Cx-26 transcripts. Progesterone treatment of these animals reversed the effects of ovariectomy. Immunofluorescence data identified Cx-26 antigen in the cell membranes of myometrial cells and in the luminal and glandular epithelium of the endometrium in the late pregnant (day 21) uterus. These data suggest that the role of gap junction formation in the myometrium in relation to the maintenance of pregnancy and the onset of labor is much more complex than previously recognized. Myometrial cell-cell communication is afforded by at least two different gap junction proteins, Cx-43 and Cx-26, that not only exhibit temporally distinct patterns of expression but are also subject to differential regulation.
Animals↗
Identification of two regulatory elements within the promoter region of the mouse connexin 43 gene.
To define the minimal sequences required for expression of the connexin 43 gene (cx43) in myometrial cells, we generated 5' deletion constructs of a fragment extending 1686 base pairs upstream and 162 base pairs downstream of the transcription start site and determined their ability to drive expression of the chloramphenicol acetyltransferase reporter gene in transfected myometrial cell lines. Our investigation revealed two cis-acting regulatory elements within this fragment. Deletion of a region extending from -102 to -92 led to an increase of the promoter activity by greater than 10-fold, indicating a presence of a repressor element. Deletion of a region extending from -72 to -62 caused a decrease of the promoter activity of a similar extent, implying the existence of a positive element. Electrophoretic mobility shift assays demonstrated that synthetic oligonucleotides derived from these two small regions can each bind with a nuclear protein(s) prepared from myometrial cells, and an introduction of three and two base substitutions into each of these oligomers was sufficient to abolish their protein binding capability. These same mutations, when incorporated in the chloramphenicol acetyltransferase constructs, diminished regulatory functions of the negative and positive elements, and the protein(s) that bind to these functional elements was found in several tissues known to express cx43 gene.
Animals↗
Reduced placental villous tree elaboration in small-for-gestational-age pregnancies: relationship with umbilical artery Doppler waveforms.
OBJECTIVE: Our purpose was to investigate the three-dimensional architecture of placental villi from normal and growth-restricted fetuses and relate findings to umbilical artery blood flow velocity waveforms. STUDY DESIGN: Placentas from term (n = 15) and preterm (n = 5) appropriately grown and term (n = 9) and preterm (n = 7) growth-restricted fetuses (birth weight < 10th percentile) were examined to determine the number of arteries per stem villus and the three-dimensional configuration of the villous trees and their vessels. Umbilical blood flow before delivery was assessed by Doppler ultrasonography. The effects of age and growth restriction were determined by two-way analyses of variance. RESULTS: Growth restriction was associated with reduced large vessel wall thickness (p < or = 0.05) but no reduction in the number of these vessels per stem villus. The volumes and surface areas of intermediate and terminal villi were reduced (p < or = 0.001), especially in preterm growth-restricted cases, where a marked reduction in diastolic blood flow velocity was observed in the umbilical artery. CONCLUSIONS: Reduced villous development may contribute to abnormal umbilical artery blood flood flow, as assessed by Doppler ultrasonography, in some cases of intrauterine growth restriction.
Blood Flow Velocity↗
The effects of maternal aerobic exercise on human placental development: placental volumetric composition and surface areas.
The histomorphometry of term placentae from women who exercised regularly throughout either the first half or all of pregnancy was compared to that of placentae from matched controls to determine if regular exercise during pregnancy produced histomorphometric evidence of altered development and transport capacity. Conventional stereological techniques were used to estimate placental volumetric composition, surface areas, and villous and vascular configurations in the three groups. Exercise confined to early pregnancy increased the parenchymal component of the placenta, total vascular volume and site-specific capillary volume and surface area. Exercise throughout pregnancy increased these and multiple other histomorphometric parameters associated with the rate of placental perfusion and transfer function. However, significant changes were confined to villi > 80 microns in diameter. The localization of both the timing of the stimulus and the anatomical sites affected indicates that regular, sustained exercise modifies placental development primarily in early and mid-pregnancy. We speculate that the lack of significant changes in the structure and configuration of the smaller villi indicates that other adaptive mechanisms, such as increased rates of placental blood flow, must be well developed by the latter portion of the mid-trimester and adequately maintain fetal oxygenation and substrate delivery throughout the third trimester.
Adult↗
Myometrial transcriptional regulation of the gap junction gene, connexin-43.
The mechanisms that enable the myometrium to switch from a state of relative quiescence during pregnancy to a muscle that is spontaneously active, very responsive to endogenous uterotonins and exhibits a high degree of cell-cell coordination are poorly understood. It is hypothesized that this switch or 'activation' of the myometrium results from the coordinated expression of a cassette of 'contraction-associated proteins'. The molecular mechanisms that regulate the expression of one of these, namely the myometrial gap junction protein connexin-43 (Cx-43), have been analysed. Myometrial Cx-43 expression is significantly increased during labour, associated with an increase in plasma oestrogen:progesterone, and positively regulated by oestrogen in non-pregnant rats. The genomic structure of the murine Cx-43 gene and the sequence of its 5' flanking sequence are reported here. This region functions as a promoter and contains several putative cis-acting elements which may be important in the regulation of Cx-43 transcription. Among these elements are several half-palindromic sequences that may function as oestrogen response elements and several AP-1 sites that may bind the transcription factors Fos and Jun. Oestrogen treatment of cells transiently transfected with a plasmid containing the Cx-43 promoter linked to the chloramphenicol acetyl transferase (CAT) gene, increased CAT activity indicating that the murine Cx-43 gene is oestrogen responsive. In addition, treatment of rats with oestrogen significantly increased mRNA encoding c-fos and c-jun in the myometrium and this occurred before any increase in Cx-43 mRNA. These data suggest that oestrogen may increase transcription of the Cx-43 gene through direct mechanisms (via the putative oestrogen response elements) or indirect mechanisms (by increased expression of c-fos and c-jun acting via the putative AP-1 sites). Since oestrogen may be an important modulator of myometrial activation, these mechanisms may be critical to the processes leading to increased synthesis of gap junctions at term and, hence, to the onset of labour.
Animals↗
Differential expression and regulation of connexin-43 and cell-cell coupling in myocytes from the circular and longitudinal layers of bovine myometrium.
The expression and localization of the gap junction protein connexin-43 (Cx-43) as well as functional coupling were studied in myocytes from the two layers of the bovine myometrium: the circular and the longitudinal layers. Intercellular communication (measured by Lucifer yellow dye transfer through gap junctions) was more intense in the circular than in the longitudinal layer of the bovine myometrium. The circular layer also exhibited a greater degree of punctuate immunofluorescence to Cx-43. Myocytes from the circular layer expressed more Cx-43 messenger RNA (mRNA; 2.38 +/- 0.46, Cx-43 over 18S RNA) than the longitudinal layer (1.46 +/- 0.48, Cx-43 over 18S RNA; P < 0.05). The modulation of Cx-43 expression by sex steroids in the two myometrial layers was tested using a pure steroidal antiestrogen, EM-139. In myocytes from the circular layer, the level of Cx-43 mRNA was decreased after treatment with 0.1 microM EM-139 (1.37 +/- 0.25, Cx-43 over 18S RNA) compared to that in untreated cells (2.38 +/- 0.46, Cx-43 over 18S RNA), representing a 40% inhibition. In parallel, cell-cell coupling and the amount of Cx-43 protein were also reduced after antiestrogen treatment. In contrast, treatment of cells from the longitudinal layer with the antiestrogen did not significantly affect the level of Cx-43 mRNA, protein, or cell-cell coupling. These data demonstrate that Cx-43 protein and mRNA are expressed and regulated differentially in myocytes from the circular and longitudinal layers of bovine myometrium. Furthermore, the circular myometrial layer may represent a preferential target for estrogen regulation of the biochemical and mechanical processes controlling contractility.
Animals↗
Increase in messenger ribonucleic acid encoding the myometrial gap junction protein, connexin-43, requires protein synthesis and is associated with increased expression of the activator protein-1, c-fos.
Expression of the myometrial gap junction protein connexin-43 (Cx-43) increases dramatically with the onset of labor in association with an increase in the plasma estrogen to progesterone ratio. Moreover, we reported that the levels of messenger RNA (mRNA) and protein encoded by the Cx-43 gene are regulated positively by estrogen and negatively by progesterone in both pregnant and nonpregnant rats. However, although the Cx-43 gene has been reported to be responsive to estrogen, it does not contain a palindromic estrogen response element. It does, however, contain a consensus activator protein-1 (AP-1)-binding site that may be of significance, as estrogen has been reported to increase expression of the AP-1 proteins, Fos and Jun, in the uterus. Therefore, we tested the hypothesis that the increase in Cx-43 mRNA levels in the myometrium during labor and after estrogen administration is mediated indirectly through induction of trans-activating factors, of which Fos and Jun are putative candidates. Treatment of nonpregnant ovariectomized rats with cyclohexamide blocked the estrogen-induced increase in Cx-43 mRNA in the myometrium, suggesting that this action of estrogen requires newly synthesized protein. Estrogen treatment alone induced an increase in mRNA encoding c-fos and c-jun in nonpregnant rats, which preceded by 2-3 h an increase in Cx-43 mRNA. Labor was also associated with a coincident expression of c-fos and Cx-43 in the myometrium, although there was no change in c-jun mRNA levels during this period. These associative data were strengthened by our observation that in paradigms in which labor was induced prematurely by ovariectomy or blocked by treatment with progesterone, changes in c-fos expression were closely matched by changes in Cx-43 mRNA. These data support our hypothesis that estrogen (and, by extension, labor-)-induced increases in Cx-43 mRNA are mediated indirectly through newly synthesized trans-activating factors. Moreover, the temporal correlation between the expression of c-fos and Cx-43 and the presence of AP-1 cis-acting elements within the Cx-43 promoter suggest that c-fos may be one of these trans-activating proteins.
Animals↗
Dexamethasone partially protects the myometrium against beta-adrenergic agonist-induced desensitization in vivo in the rat.
OBJECTIVE: Our purpose was to determine the ability of dexamethasone to prevent the onset of myometrial desensitization to beta-adrenergic agonists in vivo. STUDY DESIGN: On day 5 post partum chronically catheterized rats were randomized to receive either dexamethasone or corn oil (vehicle), followed 12 hours later by a continuous infusion of either isoproterenol or saline solution (vehicle). Uterine contractions were monitored throughout. We measured myometrial glucocorticoid receptor levels in chronically catheterized and sham-operated rats and beta 2-adrenergic receptor densities in the experimental rats before and during the infusions. RESULTS: Surgery did not lead to any decrease in glucocorticoid receptor number. Dexamethasone significantly increased the duration of myometrial responsiveness to isoproterenol compared with vehicle-pretreated rats, although agonist-induced down-regulation of beta-adrenergic receptor number was not prevented. CONCLUSION: Dexamethasone partially protects the rat myometrium from desensitization induced by the continuous infusion of beta-adrenergic agonists through mechanisms independent of the beta 2-receptor.
Adrenergic beta-Agonists↗
Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation.
The spatiotemporal distribution of two angiogenic growth factors, platelet-derived endothelial cell growth factor (PDECGF) and vascular endothelial growth factor (VEGF) were determined using immunohistochemistry on sections of human placentae from each trimester of pregnancy. In the first trimester PDECGF was detected in trophoblast and in a band in the centre of the villous core. During gestation staining spread throughout the stroma but began to weaken in trophoblast until, by term, it was found only in stroma and in some endothelial cells. VEGF was detected exclusively in cytotrophoblast during the first trimester and then in syncytiotrophoblast throughout the remainder of pregnancy. Western blot analysis revealed that PDECGF antisera bound to three bands approximately 27, 47 and 94 kDa. The lowest band was not detected in platelet lysate and may represent an alternatively processed form of this peptide in placenta. VEGF antisera bound strongly to bands approximately 36, 46, 54, 56 and 64 kDa. The intensity of most bands increased between the first and second trimesters, consistent with an increased level of angiogenesis as the placenta develops. The presence of both factors in trophoblast in early pregnancy may be indicative of the trophoblast playing an active role in influencing the development of the villous vascular network.
Blotting, Western↗
Expression of the gap junction protein connexin-43 is increased in the human myometrium toward term and with the onset of labor.
OBJECTIVES: Our aim was to determine the temporal pattern of expression of transcripts encoding the myometrial gap junction protein connexin-43 in the human myometrium during late pregnancy and with the onset of labor. We also correlated these data with levels of total connexin-43 protein and the appearance of gap junctions within the myometrial cell membrane. STUDY DESIGN: Myometrial tissue was collected during cesarean section from 27 women between 37 and 41 weeks of gestation not in labor and from 7 women between 39 and 41 weeks during active labor. The levels of connexin-43 messenger ribonucleic acid and protein were estimated by Northern and Western analysis, respectively. The appearance of gap junctions between myometrial cells was assessed by immunofluorescence of histologic sections of myometrium from these women. RESULTS: Levels of connexin-43 messenger ribonucleic acid in myometrial tissue collected from women not in labor increased (p < 0.01) between 37 and 40 weeks' gestation with a further significant increase occurring during labor (p < 0.05). The level of connexin-43 protein decreased (p < 0.05) during late pregnancy and was not increased during labor although gap junctions (which were not present during pregnancy) did appear in the myometrial cell membrane during labor. CONCLUSIONS: These data suggest that the mechanisms responsible for the increased myometrial cell-cell communication necessary for the development of effective labor contractions likely involves regulation at the level of both messenger ribonucleic acid and gap junction formation in the cell membrane.
Animals↗
Localization of endoglin, a transforming growth factor-beta binding protein, and of CD44 and integrins in placenta during the first trimester of pregnancy.
Endoglin is an integral membrane glycoprotein that binds transforming growth factor-beta 1 (TGF beta 1) with high affinity and is predominantly expressed on human endothelial cells. Characterization of this homodimeric protein from human term placenta has shown that it is particularly abundant on the syncytiotrophoblast. Immunofluorescence staining of sections of first trimester placenta now reveals that endoglin is found at even higher levels on the syncytiotrophoblast of samples ranging from 6 to 12 wk of gestation. Very low levels are observed on the undifferentiated cytotrophoblast cells that can be identified by their expression of the alpha 6 beta 4 integrin, a receptor for laminin. Within the villi, blood vessels and stromal cells are negative for endoglin but positive for alpha 1 beta 1 integrin, a receptor for collagens and laminin. Stromal cells also express CD44, a hyaluronic acid receptor. Of particular interest is the up-regulation of endoglin expression in the transition from polarized undifferentiated to non-polarized intermediate cytotrophoblasts (CTB) as the cells align in columns to invade the uterus. This occurs in parallel with the acquisition of alpha 5 beta 1 integrin (fibronectin receptor) and precedes the loss of alpha 6 beta 4 integrin. CD44 and alpha 1 beta 1 integrin are noticeably absent from the CTB within the columns but are expressed at very high levels throughout the placental bed. Endoglin is undetectable within the decidua; thus, intermediate CTB that have invaded the placental bed express alpha 5 beta 1 integrin and cytokeratins but not endoglin.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗