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At least 649 records · Page 36Linked to original sources
PubMed2003

Parp1-deficiency induces differentiation of ES cells into trophoblast derivatives.

Embryonic stem (ES) cells deficient in the enzyme poly(ADP-ribose) polymerase (Parp1) develop into teratocarcinoma-like tumors when injected subcutaneously into nude mice that contain cells with giant cell-like morphology. We show here that these cells express genes characteristic of trophoblast giant cells and thus belong to the trophectoderm lineage. In addition, Parp1(-/-) tumors contained other trophoblast subtypes as revealed by expression of spongiotrophoblast-specific marker genes. The extent of giant cell differentiation was enhanced, however, as compared with spongiotrophoblast. A similar shift toward trophoblast giant cell differentiation was observed in cultures of Parp1-deficient ES cells and in placentae of Parp1(-/-) embryos. Analysis of other cell lineage markers demonstrated that Parp1 acts exclusively in trophoblast to suppress differentiation. Surprisingly, trophoblast derivatives were also detected in wildtype tumors and cultured ES cells, albeit at significantly lower frequency. These data show that wildtype ES cells contain a small population of cells with trophectoderm potential and that absence of Parp1 renders ES cells more susceptible to adopting a trophoblast phenotype.

Animals↗
PubMed2002

Decreased progesterone receptor expression in the intermediate trophoblastic cells of spontaneous abortions.

OBJECTIVE: To determine whether there are differences in the expression of progesterone receptor (PR) in intermediate trophoblastic cells of pregnancies ending in either spontaneous abortion (SAB) or elective abortion. DESIGN: Immunohistochemical identification of PR in intermediate trophoblastic cells. SETTING: Academic medical center. PATIENT(S): Subjects were 86 patients who either underwent first trimester SAB or elective abortion. INTERVENTION(S): All SAB and elective abortion specimens were serially sectioned and immunohistochemically stained for PR and for melanoma cell adhesion molecule. Melanoma cell adhesion molecule immunohistochemical staining was used as a sensitive and specific marker to identify intermediate trophoblastic cells on the adjacent tissue section. MAIN OUTCOME MEASURE(S): The PR staining of intermediate trophoblastic cells by semiquantitative immunostaining score. RESULT(S): The PR expression in intermediate trophoblastic cells was significantly greater in elective abortion specimens than in SAB specimens. When controlling for estimated gestational age, the difference in PR expression was even greater. CONCLUSION(S): The quantity of PR in intermediate trophoblastic cells is significantly less in SAB when compared to elective abortion pregnancies. Although it is unknown whether this is a primary or secondary event, this information may be an important finding in attempting to characterize both the molecular etiology of implantation and the molecular pathophysiology of SAB.

Abortion, Induced↗
PubMed1999

Lymphoid cell apoptosis induced by trophoblastic cells: a model of active foeto-placental tolerance.

To test the hypothesis that CD95-L (Fas-L) present on trophoblastic cells plays a part in establishing foeto-placental tolerance by inducing apoptosis of immune defence cells, we cocultured trophoblasts with lymphoid cells and scored the frequency of cell death in these cultures. We prepared human trophoblastic cells from term placentas removed by C-section and placed them in culture for 48 h before introducing the lymphoid cells. We added Jurkat cells, a CD3 + lymphoid cell line, or purified T cells from human blood to the cultured trophoblasts and monitored apoptosis by electron microscopy and flow cytometry after TUNEL or annexin V labelling. The frequency of cell death in the CD3 + cell population was higher when the lymphoid cells were cocultured with trophoblastic cells than when they were cultured alone. This frequency increased with time but was reduced when anti-CD95-L antibodies were added to the culture medium. Cell death was less frequent in the lymphoid cell population when trophoblasts were replaced with human fibroblasts not expressing CD95-L.

Apoptosis↗
PubMed2006

Trophoblast stem cells.

At the first cell fate decision in mammalian development, the origins of trophoblast and embryonic cell lineages are established as the trophectoderm and the inner cell mass (ICM) in the blastocyst. In the trophoblast cell lineage, a subset of the trophectoderm cells maintains the capacity to proliferate and contribute to the extraembryonic ectoderm, the ectoplacental cone, and the secondary giant cells of the early conceptus after implantation, and finally they produce the entire trophoblastic population in the mature placenta. The stem cell population of the trophectoderm lineage can be isolated and maintained in vitro in the presence of fibroblast growth factor 4, heparin, and a feeder layer of mouse embryonic fibroblast cells. These apparently immortal stem cells in culture are termed trophoblast stem (TS) cells, and exhibit the potential to differentiate into multiple trophoblastic cell types in vitro, as well as in vivo. Even after multiple passages, TS cells retain the ability to participate in the normal development of chimeras and contribute exclusively to the trophoblastic component of the placenta and of the parietal yolk sac. The fate of TS cells is strikingly in contrast to that of embryonic stem cells, which never contribute to these tissues. In this chapter, detailed protocols for the isolation and establishment of TS cell lines from blastocysts and their maintenance are described.

Animals↗
PubMedDate not supplied

Cross-reactions between cell surface membrane antigens of human trophoblast and cancer cells.

This report describes cross-reactivity between cell surface membrane antigens of human trophoblast and certain transformed cells. Heterologous antisera were raised to chaotrope extracted, intact and solubilized trophoblast microvillous pellets. Antisera to microvilli, after absorption with human erythrocytes and serum proteins, reacted with trophoblast, endothelium and stromal cells of chorionic villi as well as with all other human tissues tested. This group of antigens was designated TA2. Further absorptions of the TA2 antisera with normal human tissues such as liver, kidney or peripheral blood leucocytes, removed all immunofluorescent reactivity except for the apical aspect of syncytiotrophoblast and membranes of the human transformed cell lines HEp-2, AV3 and Chang liver. This group of antigens was designated TA1. Absorption with trophoblast membrane pellets removed all TA1 and TA2 antibody activity. Rabbit antisera raised to the first peak of DOC solubilized syncytiotrophoblast microvilli were shown to have identical patterns of immunofluorescent reactivity to that described for TA1. Cytotoxicity assays with the antisera confirmed the immunofluorescent findings of species specificity and the inability to absorb out reactivity to the cell lines expressing trophoblast cross-reactive antigens with normal tissues. Exhaustive absorptions with AV3 and HEp-2 cell lines removed all immunofluorescent and cytotoxic activities. We propose that the trophoblast cross-reactive antigens present on certain transformed cell lines represent an adaptive response of tumour cells to natural selection pressures as a biological response to resist immunological recognition and rejection by the host.

Absorption↗
PubMedDate not supplied

An immunohistological comparison of the secretory capacity of villous and extravillous trophoblast in the human placenta.

Using an immunoperoxidase technique the localization of hCG, hPL, SP1, PAPP-A and PP5 within villous and extravillous trophoblast has been studied. The villous syncytiotrophoblast appears to be the sole significant source of hCG, SP1, PAPP-A and PP5 but hPL is also present in the infiltrating extravillous trophoblast. Within the interstitial extravillous trophoblast the proportion of cells staining positively for hPL increases progressively as the cells extend deeper into the uterine tissues but all the vascular extravillous trophoblast within the lumina of the spiral arteries stains positively for hPL at all levels within the decidua and inner myometrium. It is not clear why the synthetic capacity of the infiltrating trophoblast is limited to the production of hPL. We suggest that this might be indicative of selectivity of a specific subpopulation of cytotrophoblastic cells. It is unlikely that the physiological effects of infiltrating trophoblast are mediated by hPL, this substance being probably only a marker of a cell population with a particular invasive capacity.

Chorionic Gonadotropin↗
PubMed1996

Induction of erythrophagocytic activity in cultured mouse trophoblast cells by phorbol myristate acetate and all-trans-retinal.

Phorbol myristate acetate (PMA) and all-trans-retinal (retinal) were evaluated as possible phagocytic stimulators of cultured, post implantation, trophoblast cells. Ectoplacental cones dissected from 7.5 day-old mouse embryos provided the source of trophoblastic cells. Co-cultures were performed using stimulated and non-stimulated trophoblast cells and erythrocytes under standard conditions. Phagocytic activity was expressed as the total number of phagocytic cells per ectoplacental cone, and as phagosomic vacuoles per trophoblast giant cell, either in the presence or absence of the stimulators. Both chemical agents had similar effects, less than 12 h after stimulation, statistically significant numbers of erythrophagosomes appear in the trophoblast giant cells (TGC). These findings demonstrate that TGC, like neutrophils and macrophages, can be activated to phagocytosis by exogenous factors. This enhanced activity may result from the generation and release of reactive oxygen species. In conclusion, our data suggest that, because stimulation was provided, the remarkable in vivo phagocytic activity of the trophoblast can be maintained under in vitro conditions, allowing study of the pathways and regulatory steps involved in this process.

Animals↗
PubMed1996

The effect of hypoxia on term trophoblast: hormone synthesis and release.

Isolated trophoblast in culture remained viable when exposed to severe hypoxia (Po2 12-14 mmHg) for at least 72 h as indicated by trypan blue exclusion and the synthesis and secretion of metabolically labelled proteins. However, release of hCG, hPL, progesterone and estradiol was reduced to < 10 per cent when compared to trophoblast in normoxia (Po2 120-130 mmHg). hCG mRNA was also reduced demonstrating interruption of synthesis at transcription. Acute exposure to hypoxia (2 h) suppressed progesterone release but not hCG, whereas inhibitors of oxidative phosphorylation suppressed hCG release but not progesterone. hCG release increases progressively during culture in normoxia, peaking at 72 h. Exposure of trophoblast to hypoxia for 48 h after 24, 48 and 72 h in normoxia interrupted this progression but did not suppress hCG release. Progesterone release, in contrast, was reduced by hypoxia. Exogenous dibutyryl cAMP increased hCG and progesterone release by normoxic trophoblast but not by hypoxic cells. Trophoblast returned to normoxia after 24 h in hypoxia increased hCG and progesterone release, suggesting early recovery. Conservation of oxygen and ATP by reducing hormone synthesis may contribute to survival of trophoblast in hypoxia.

Cell Hypoxia↗
PubMedDate not supplied

Analysis of MHC class I expression in equine trophoblast cells using in situ hybridization.

Down-regulation of major histocompatibility complex (MHC) genes by trophoblast cells is considered to be a primary mechanism preventing maternal immune rejection of the fetal-placental unit in mammalian pregnancy by rendering these cells, which form the primary barrier between mother and fetus, relatively non-antigenic. In situ hybridization with probes encoding human and horse MHC class I genes was used to characterize the pattern of MHC class I mRNA expression in the various forms of horse trophoblast. Strong hybridization signals were observed in the invasive trophoblast cells of chorionic girdle tissue. In contrast, no hybridization signal specific for MHC class I mRNA transcripts was observed in the descendent endometrial cup trophoblast cells. In the non-invasive trophoblast cells of the allantochorion, no hybridization signals specific for horse MHC class I mRNA transcripts were consistently detected. In parallel to the in vivo results, strong hybridization signals were observed in the small, mononuclear cells present in chorionic girdle cell explant cultures, but not in the population of large binucleate cells corresponding to endometrial cup cells. The results obtained using in situ hybridization are consistent with the hypothesis that expression of MHC class I genes may be controlled at the transcriptional level in horse invasive and non-invasive trophoblast cells, and suggest that down-regulation of MHC class I antigen expression in endometrial cup cells may be accomplished by the same mechanisms in vivo and in vitro.

Animals↗
PubMedDate not supplied

Evidence for basic fibroblast growth factor as a crucial angiogenic growth factor, released from human trophoblasts during early gestation.

The objective of this study was to clarify the possible angiogenesis-promoting factors from human trophoblasts in early stage gestation. The existence of angiogenic growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in the condition medium from human villous trophoblasts was determined. Biological activity of angiogenic growth factors released by trophoblasts was examined using vascular endothelial cell lines. The condition medium from trophoblasts enhanced the growth of endothelial cells. Although cultured trophoblasts exhibited immunoreactive products for both bFGF and VEGF in the cytoplasm, only bFGF was detected in the condition medium by ELISA. The growth-enhancing activity of the condition medium was eliminated completely by the addition of anti-bFGF antibody but not with anti-VEGF antibody. Thus, trophoblastic cells seem to play an important role in extensive angiogenesis occurring in early gestation, mainly by releasing bFGF but not VEGF.

Adult↗
PubMedDate not supplied

Interferon-gamma induces differentiation of ectoplacental cone cells to phenotypically distinct trophoblasts.

Maturation of the murine ectoplacental cone results in the development of the placental tissue which essentially consists of two trophoblastic zones, the spongiotrophoblast and labyrinthine trophoblast. In this study we attempted to investigate the action of cytokines on ectoplacental cone cell differentiation to mature trophoblast cells. After determining the cellular composition of the ectoplacental cone cell suspensions based on the expression of cytokeratin, vimentin, Mac-1, class I and class II MHC antigens, the cells were exposed to the differentiation-inducing cytokines IL-3, GM-CSF, CSF-1 and IFN-gamma. From the four factors employed, only IFN-gamma increased the levels of cytokeratin-positive cells without inducing Mac-1 expression. IL-3 increased the percentages of cytokeratin as well as Mac-1- and vimentin-positive cells whereas GM-CSF and CSF-1 preferentially promoted an increase of the Mac-1 and vimentin markers. For further analysis, ectoplacental cone cells were negatively selected for Mac-1, class I and class II antigens to exclude non-trophoblastic contaminants and thereafter treated with the same cytokines. We show here that only IFN-gamma leads the sorted ectoplacental cone cells to a pure trophoblastic population composed of 100% cytokeratin-positive cells. The specificity of IFN-gamma on this differentiation pathway is strengthened by the fact that murine maternal serum on the day of EC formation contains high levels of this cytokine, suggesting that its natural presence supports - at least phenotypically - the in vivo differentiation of EC cells to trophoblasts.

Animals↗
PubMedDate not supplied

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on chorionic gonadotropin secretion by human trophoblasts.

This study tests the idea that the environmental toxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), affects human trophoblast differentiation and alters the secretion of chorionic gonadotropin (CG). Primary cultures of cytotrophoblast cells were incubated under differentiation-inducing and nondifferentiation-inducing conditions in the presence or absence of different concentrations of TCDD. Levels of immunoreactive CG as well as bioactive CG were measured in culture supernatants. TCDD caused a significant increase in the secretion of immunoreactive CG from differentiated trophoblast cultures but had no effect on the secretion of bioactive hormone. The net effect was a TCDD-dependent reduction in the CG bioactive/immunoreactive (B/I) ratio for differentiated trophoblast cultures. TCDD had no effect on immunoreactive or bioactive CG secretion by undifferentiated trophoblasts. Immunocytochemical studies showed that TCDD had no effect on the morphologic differentiation of trophoblast cells as determined by staining nuclei and desmosomal proteins. On the other hand, immunocytochemical staining for CG was increased in cells exposed to TCDD compared to control cells. These in vitro results support earlier in vivo studies in macaques suggesting that trophoblast is a target for TCCD and that TCDD-induced early pregnancy loss is accompanied by a decrease in the CG B/I ratio.

Cell Nucleus↗
PubMed2003

Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells.

OBJECTIVES: Recent evidence indicates that preeclampsia is associated with the presence of autoantibodies capable of activating the angiotensin II receptor, AT1. We sought to evaluate the role of AT1 agonistic autoantibodies (AT1-AA) in two major features of preeclampsia-increased plasminogen activator inhibitor-1 (PAI-1) production and shallow trophoblast invasion. METHODS: This study included 38 pregnant patients, 20 of whom had severe preeclampsia and 18 normotensive individuals. Immunoglobulin (Ig)G was purified from these individuals, and the presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of cultured rat neonatal cardiac myocytes. Immortalized human trophoblasts were chosen to study PAI-1 production and secretion after treatment with IgG from normotensive and preeclamptic women. An in vitro Matrigel invasion assay was used to test the effect of AT1-AA on the invasive properties of human trophoblasts. Losartan and cyclosporin A were used to determine whether the AT1-AA-induced stimulation of PAI-1 secretion is through the AT1 receptor and the calcineurin-nuclear factor of activated t-cells (NFAT)-dependent pathway. RESULTS: The results show that IgG from 18 of 20 severely preeclamptic women stimulated increased cardiomyocyte contraction rates of 20-40 beats per minute. A significant stimulation of PAI-1 secretion from human trophoblasts was observed with IgG from the same 18 of 20 patients with severe preeclampsia. Of IgG obtained from 18 normotensive pregnant patients, only two showed a relatively low level of biologic activity in the cardiomyocyte contraction and PAI-1 secretion assays. Activation of AT1 receptors by AT1-AA was blocked by losartan (an AT1 receptor antagonist) and by a seven amino acid peptide corresponding to a sequence present on the second extracellular loop of the AT1 receptor. Activation of AT1 receptors by AT1-AA resulted in decreased trophoblast invasiveness as determined by the in vitro Matrigel invasion assay. Additional data indicate that AT1 receptor activation by AT1-AA is followed by the downstream activation of the calcium-dependent calcineurin-NFAT signaling pathway leading to increased PAI-1 gene expression. CONCLUSION: Our findings suggest that maternal autoantibody with the ability to activate AT1 receptors may account for two features of preeclampsia, increased PAI-1 production and shallow trophoblast invasion.

Animals↗
PubMedDate not supplied

Differentiation-dependent changes in human trophoblast expression of decay-accelerating factor are modulated by 3',5' cyclic adenosine monophosphate.

OBJECTIVE: Decay-accelerating factor (DAF) is a complement regulatory protein that prevents complement-mediated cell lysis. Its expression in human trophoblasts depends on their anatomic location and gestational age. The mechanisms that govern the regulation of its expression in trophoblasts are not understood. The objective of the present study was to investigate the effects of trophoblast differentiation and cyclic adenosine monophosphate (cAMP) on DAF expression. METHODS: Human trophoblasts were isolated from chorionic villi, cultured, and harvested at timed intervals for total RNA extraction and Northern analysis. Expression of DAF was also assessed by immunocytochemistry. In some cultures, the trophoblasts were exposed to the cAMP agonists 8-bromo-cAMP and Sp-cAMPs or the antagonist Rp-cAMPs. RESULTS: Expression of DAF mRNA increased as the cells differentiated in culture, with the 2.2-kb transcript of membrane-bound DAF appearing first. As differentiation proceeded, the 1.5-kb transcript became the predominant mRNA form. Exposure of the cells to Rp-cAMPs delayed this process; 8-bromo-cAMP accelerated it. Sp-cAMPs selectively up-regulated the 2.2-kb mRNA transcript. Immunocytochemistry confirmed the effects of differentiation on DAF protein expression. CONCLUSION: Expression of DAF in human trophoblasts is dependent on the state of cell differentiation, and cAMP is an intracellular modulator of this process. This effect may be mediated through alternative processing of DAF mRNA in its 3'UT region, which in turn affects mRNA stability.

Blotting, Northern↗
PubMedDate not supplied

[The 2 differentiation pathways of the human trophoblast].

The trophoblast is the major component of the human placenta. It is directly involved in blastocyst implantation and in feto-placental growth and development. Human trophoblast follows two major pathways of differentiation: the villous trophoblast, bathing in maternal blood of intervillous spaces and involved in matemo-fetal exchanges and in placental endocrine functions; the extra-villous trophoblast involved in uterine spiral arteries remodeling and in the placental anchorage into the uterine wall. It is essential to understand the cellular and molecular mechanisms involved in human trophoblast differentiation: cellular proliferation, migration, invasion and differentiation by cell-cell fusion. Abnormal trophoblast differentiation is implicated in the major pathologies of human pregnancy such as pre-eclampsia and intrauterine growth retardation.

Cell Differentiation↗
PubMed2003

Evidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway.

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration.

Biomarkers↗
PubMed2002

Gestational trophoblastic disease: one more risk in adolescent pregnancy.

BACKGROUND: An evaluation of the performance of a Referral Center in the diagnosis, treatment and follow up of adolescents with gestational trophoblastic disease. METHODS: In a 13-year prospective cohort study, between March 1987 and March 2000, 124 adolescents with gestational trophoblastic disease were followed up and/or treated by a multidisciplinary team. Adolescents underwent strict clinical and laboratory control after mole evacuation to guarantee adhesion to follow up, early diagnosis, and prompt treatment of persistent disease. The Student-Fischer t-test and the chi-square test were used for the statistic analysis of the results. RESULTS: Adolescents represented 21.3% of the 583 patients with gestational trophoblastic disease: 102 (82.3%) had uncomplicated hydatidiform moles, and 22 (17.7%) underwent chemotherapy for persistent gestational trophoblastic disease or a gestational trophoblastic tumor. Complications were diagnosed earlier (p < 0.001) in patients managed and treated at the referral center. Of the adolescents with complications, 81.8% were low risk, 54.5% were at the International Federation of Gynecology and Obstetrics stage I, and 90.9% were treated with chemotherapy only. Time to remission and follow up were shorter for uncomplicated hydatidiform moles (9.8 +/- 3.4 weeks and 8.8 +/- 1.8 months, respectively) than for persistent disease (16.2 +/- 5.8 weeks and 45 +/- 24.5 months, respectively). Adhesion to follow up was similar in the two groups (84.2% and 91.8%). To this date, 50% of the adolescents have had one or more gestations, and 82% of these pregnancies were normal. CONCLUSIONS: Adolescents comprise approximately 20% of all gestational trophoblastic disease patients and have high adhesion to follow up. The disease did not affect their reproductive capacity, and chances of a normal subsequent gestation were high.

Adolescent↗
PubMed2003

Evidence for a correlation between trophoblast invasiveness and STAT3 activity.

PROBLEM: Extravillous trophoblast cells are capable of invading decidual tissue during early pregnancy. This property is reminiscent of cancer cells. The invasiveness of trophoblasts, however, extends only to a well-regulated limit. Signal transduction processes underlying this phenomenon are as yet poorly characterized. Many factors involved in trophoblast invasiveness are known to trigger intracellular signaling cascades in other cell types that ultimately lead to the activation of signal transducers and activators of transcription (STATs). STAT3 activity was recently found related to the malignant phenotype of different tumor cells and potentially contributes to their invasive properties. METHOD OF STUDY: We investigated the status of STAT3 activity in ex vivo trophoblast cells from first trimester and term placentae employing an electrophoretic mobility shift assay (EMSA) and compared it with that of a highly malignant choriocarcinoma cell line. RESULTS: Specific DNA binding activity of two STAT3 variants (STAT3alpha and beta) was observed in immature trophoblasts and appeared to be lost in term placentae. The malignant phenotype of choriocarcinoma cells coincides with a high degree of STAT3 activity. CONCLUSION: These results suggest a connection between STAT3 activity and trophoblast invasiveness.

Base Sequence↗