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PubMed1993

Mechanisms of murine trophoblast interaction with laminin.

Implantation of the mouse embryo depends on the interaction of the trophoblast and the uterine environment, which includes an extracellular matrix with abundant amounts of laminin. The experiments reported here analyzed the interaction of trophoblast with laminin in vitro. Secondary trophoblast attachment and spreading on laminin matrices was competitively inhibited in the presence of the laminin peptides YIGSR (Tyr-Ile-Gly-Ser-Arg), RGD (Arg-Gly-Asp), and IKVAV (Ile-Lys-Val-Ala-Val). Substrates of multiple, but not single, peptides supported attachment and spreading of trophoblast. The presence of laminin-binding proteins on trophoblast cell surfaces were detected by immunofluorescence using antiserum directed against a fusion protein encoded by the full-length clone for the 32-kDa laminin-binding protein. Immunoblotting with the same antiserum identified immunoreactive proteins of 33, 41, 45, 62, and 76 kDa in trophoblast lysates. The antiserum also inhibited the spreading of trophoblast on laminin matrices.

Amino Acid Sequence↗
PubMed1993

A porcine trophoblast cell line that secretes growth factors which stimulate porcine macrophages.

We have previously described experiments in both the mouse and the human indicating that cytokines capable of activating macrophages (colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-3 [IL-3]) are produced by, and/or stimulatory of, trophoblast cells in these species. In contrast to the complex hemochorial placenta of the mouse and humans, the pig has a simple diffuse type of placenta, designated as epitheliochorial. To determine whether similar phenomena might not apply to the porcine pregnancy, we have isolated a cell line, designated Jag-1, from the trophoblastic tips of Day 14 porcine embryos. We report here that this cell line is cytokeratin-positive, vimentin-negative, and therefore of epidermal origin. It also shares various morphological characteristics with porcine trophoblast as demonstrated at both the light and electron microscopic levels. In addition, Jag-1 cells and primary trophoblast tissue from Day 14 blastocyst do not express classical major histocompatibility (MHC) class I and class II antigens, a unique feature of trophoblast in many species. To determine the ability of this cell line to produce cytokines, we have developed an assay for porcine macrophage growth factors that utilizes uptake of tritiated thymidine. This assay responds positively to recombinant bovine GM-CSF and, more importantly, detects a similar activity in supernatants of the porcine trophoblast cell line and of Day 14 blastocysts. Thus porcine trophoblast cells, like their murine and human counterparts, produce and potentially interact with lymphohematopoietic cytokines that are traditionally associated with macrophages.

Animals↗
PubMed1995

Human intermediate trophoblasts express chorionic gonadotropin/luteinizing hormone receptor gene.

Human cyto- and synchtiotrophoblasts have recently been shown to contain functional hCG/LH receptors. The present study investigated whether human intermediate trophoblasts also contain these receptors. Six implantation sites from 4-8 wk of pregnancy were processed for in situ hybridization for hCG/LH receptors coupled with immunocytochemistry for human placental lactogen (hPL), an endocrine marker for intermediate trophoblasts. In addition, the sections were also double-immunostained for hCG/LH receptor and hPL proteins. The results showed that some but not all the intermediate trophoblasts contained hCG/LH receptors. The intermediate trophoblasts in endovascular locations contained more receptors than those in perivascular locations. Villus syncytiotrophoblasts contained the highest level of receptors, followed by intermediate trophoblasts in endovascular and perivascular locations and then villus cytotrophoblasts. These data, demonstrating the presence of hCG/LH receptors in intermediate trophoblasts, suggest a possible role for hCG in trophoblast invasion and maternal recognition of pregnancy.

Embryo Implantation↗
PubMed1999

Expression of the erythropoietin receptor by trophoblast cellsin the human placenta.

Nonclassical sites of erythropoietin (EPO) and erythropoietin receptor (EPO-R) expression have been described that suggest new physiological roles for this hormone unrelated to erythropoiesis. The recent finding of EPO expression by trophoblast cells in the human placenta prompted us to consider whether these cells also express EPO-R. With use of immunocytochemistry, EPO-R was identified in villous and extravillous cytotrophoblast cells, as well as in the syncytiotrophoblast at all gestational ages. EPO-R was also expressed by cells within the villous core, including endothelial cells of fetoplacental blood vessels. Placental tissues and isolated and immunopurified trophoblast cells, as well as trophoblast-derived choriocarcinoma Jar cells, expressed immunoreactive EPO-R on Western blot. EPO-R mRNA was also detected in the same placental tissues and trophoblast cells by nested-primer reverse transcription-polymerase chain reaction. Finally, EPO-R was functional insofar as the receptor was phosphorylated on tyrosine residues in response to exogenous EPO treatment of cultured trophoblast or Jar cells. Thus, the present findings support the hypothesis that trophoblast cells of the human placenta express EPO-R. In view of these results, taken together with previous work demonstrating EPO expression by the same cells, an autocrine role for this hormone in the survival, proliferation, or differentiation of placental trophoblast cells is proposed.

Blotting, Western↗
PubMed2000

Participation of the mouse implanting trophoblast in nitric oxide production during pregnancy.

While considerable progress has been made in elucidating nitric oxide (NO) regulatory mechanisms in the later stages of gestation, much less is known about its synthesis and role during embryo implantation. Thus, to evaluate the participation of the trophoblast in the production of NO during this phase, this study focused on NADPH-diaphorase activity and the distribution of NO synthase isoforms (NOS) using immunohistochemistry in pre- and postimplantation mouse embryos in situ and in vitro, as well as on NO production itself, measured as total nitrite, in trophoblast culture supernatants (Griess reaction). No NADPH-diaphorase activity was found in preimplanting embryos except after culturing for at least 48 h, when a few trophoblastic giant cells were positive. Conversely, postimplantation trophoblast cells either lodged into the implantation chamber (in situ) or after culturing (in vitro) showed intense NADPH-diaphorase activity. Also in the postimplantation trophoblast, the endothelial and inducible NOS (eNOS and iNOS) isoforms were immunodetected, under both in situ and in vitro conditions, although in different patterns. Extracts of ectoplacental cone also revealed bands of 135 and 130 kDa on SDS-PAGE that reacted with anti-eNOS and anti-iNOS, respectively, on Western blot. Analysis of the culture supernatant demonstrated that the nitrite concentration was 1) proportional to the number of cultured trophoblast cells, 2) almost completely abolished in the presence of N(omega)-nitro-L-arginine methyl ester, and 3) increased 2-fold in cultures stimulated with gamma-interferon. These results strongly suggest the production of NO from constitutive and inducible isoforms of NOS by the implanting mouse trophoblast. They also emphasize the possibility of the participation of these cells in vasodilatation and angiogenesis, and in cytotoxic mechanisms involved in the intense phagocytosis of injured maternal cells, which occur during the implantation process.

Animals↗
PubMed1987

Intermediate trophoblast in germ cell neoplasms.

One-hundred-twenty-four germ cell tumors and 11 gestational choriocarcinomas were assessed immunohistochemically for the presence of the following placental markers: human chorionic gonadotrophin, human placental lactogen, and pregnancy-specific beta-1 glycoprotein, and for the expression of cytokeratin. A total of 40 cases contained syncytial trophoblastic cells, large mononuclear cells, or both. These cases included all gestational choriocarcinomas and choriocarcinomatous foci in 11 mixed germ cell tumors, 14 embryonal carcinomas, and four seminomas. Syncytial trophoblastic cells reactive for cytokeratin were identified in all choriocarcinomas, 12 embryonal carcinomas, and two seminomas. Human placental lactogen-reactive syncytial trophoblastic cells were observed in nine gestational choriocarcinomas, 10 choriocarcinomatous foci in mixed germ cell tumors, four embryonal carcinomas, and one seminoma. Pregnancy-specific beta-1 glycoprotein-reactive syncytial trophoblastic cells were seen in 10 gestational choriocarcinomas, all choriocarcinomatous foci in mixed germ cell tumors, 11 embryonal carcinomas, and one seminoma. Cytotrophoblasts, as expected, were identified only in choriocarcinomas. Cytokeratin-reactive cytotrophoblast was seen in all gestational choriocarcinomas and 10 choriocarcinomatous foci in mixed germ cell tumors. Human chorionic gonadotrophin-reactive cytotrophoblast was observed in two gestational choriocarcinomas and three choriocarcinomatous foci in mixed germ cell tumors. Cytotrophoblast was uniformly nonreactive for human placental lactogen and pregnancy-specific beta-1 glycoprotein. Cytokeratin-reactive large mononuclear cells were observed in 10 gestational choriocarcinomas, all choriocarcinomatous foci in mixed germ cell tumors, five embryonal carcinomas, and three seminomas. Human placental lactogen-reactive large mononuclear cells were identified in nine gestational choriocarcinomas, seven choriocarcinomatous foci in mixed germ cell tumors, one embryonal carcinoma, and one seminoma. Pregnancy-specific beta-1 glycoprotein-reactive large mononuclear cells were present in 10 gestational choriocarcinomas, 10 choriocarcinomatous foci in mixed germ cell tumors, two embryonal carcinomas, and two seminomas. Because of morphologic and immunohistochemical similarities of large mononuclear cells with intermediate trophoblast of the normal placenta and gestational trophoblastic neoplasms, we propose that the large mononuclear cells in gonadal and extragonadal germ cell neoplasms are equivalent to the intermediate trophoblast.

Choriocarcinoma↗
PubMed2001

Immunohistochemical expression analysis of inhibin-alpha and -beta subunits in partial and complete moles, trophoblastic tumors, and endometrial decidua.

The expression of inhibin-alpha subunit has been described in normal placentas, hydatidiform moles, and trophoblastic tumors. We performed a double immunohistochemical expression analysis of inhibin-alpha and inhibin-beta subunits in a cytogenetically well characterized series of 21 complete and 22 partial hydatidiform moles, 2 placental site trophoblastic tumors, and one choriocarcinoma. Syncytiotrophoblastic cells were consistently inhibin-alpha and inhibin-beta positive in all hydatidiform moles and in the one choriocarcinoma. Cytotrophoblast was negative for both subunits in all trophoblastic lesions studied. While villous intermediate trophoblastic cells were consistently inhibin-alpha negative in all hydatidiform moles, focal inhibin-beta immunoreactivity was detected in villous intermediate trophoblast in approximately one third of complete and partial hydatidiform moles. Decidual stromal cells in 40 hydatidiform moles were inhibin-alpha and inhibin-beta positive in approximately one third of cases. Both placental site trophoblastic tumors were inhibin-alpha positive but inhibin-beta negative. Our findings indicate that inhibin-alpha and -beta subunits are consistently coexpressed in syncytiotrophoblast in complete and partial moles. Immunohistochemical detection of inhibin subunits may be useful in the differential diagnosis of trophoblastic lesions.

Choriocarcinoma↗
PubMed1984

Recruitment of cytotoxic cells by ectopic grafts of xenogeneic, but not allogeneic, trophoblast.

In previous studies we showed that survival of Mus caroli embryos in the Mus musculus uterus was dependent on trophoblast genotype; M musculus trophoblast was protective while M caroli trophoblast was not. In this report we compare the immune response of M musculus to ectopic grafts of pure trophoblast of M caroli and M musculus genotypes to elucidate further differences between the properties of trophoblast from the two species that might account for the failure of M caroli trophoblast to protect the fetus. Grafts of M caroli or DBA/2J ectoplacental cone (EPC) or embryonic tissue (E) were placed beneath the renal capsule of Ha(ICR) mice that were untreated or had been immunized with M caroli lymphocytes or with P815 mastocytoma cells. No consistent morphological difference could be demonstrated between the xenografts and allografts by gross or histological examination. Cellular infiltration of allogeneic and xenogeneic EPC graft sites occurred in immunized mice within 5 days of grafting. Cells specifically cytotoxic to M caroli lymphoblasts were isolated from the xenogeneic graft sites, but no allogeneically sensitized cytotoxic cells could be demonstrated. These results show that xenoantigens expressed on trophoblast induce a cytotoxic immune response more readily than alloantigens.

Animals↗
PubMed2003

Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells.

We recently identified two novel aminopeptidases, placental leucine aminopeptidase (P-LAP) and adipocyte-derived leucine aminopeptidase (A-LAP). Enzymatically, P-LAP degrades oxytocin, vasopressin, and angiotensin III, while A-LAP degrades angiotensin II and kallidin. In this study we investigated the expression and localization of P-LAP and A-LAP in human trophoblastic cells in the normal placenta (n = 26), gestational choriocarcinoma (n = 8), and placental site trophoblastic tumor (n = 3). On immunoblot analysis both P-LAP and A-LAP proteins were detected in normal placenta and five choriocarcinoma tissues, as well as in two choriocarcinoma cell lines. Immunohistochemical staining of normal placental tissues demonstrated that P-LAP was not only localized in villous syncytiotrophoblasts but also highly expressed in extravillous trophoblasts (EVTs) invading the decidua or maternal spiral arteries. The expression level of P-LAP on these invasive EVTs reached a maximum during the late first to second trimesters of pregnancy, and it decreased in the third trimester. Similarly, A-LAP was strongly expressed in EVTs invading the decidua or spiral arteries in the second trimester of pregnancy, while it was weakly or moderately expressed in villous cytotrophoblasts or EVTs located in the cell columns. These two aminopeptidases were more strongly expressed in all eight choriocarcinomas and three placental site trophoblastic tumors and mainly localized to the intermediate-type trophoblastic tumor cells invading the uterine myometrium or stromal vessels. In summary P-LAP and A-LAP were predominantly expressed in the invasive phenotype of EVTs during placentation, as well as in the invasive tumor cells of trophoblastic neoplasms. These results suggest the involvement of these aminopeptidases in invasiveness of both normal and malignant intermediate-type trophoblasts possibly through degradation of specific peptide substrates.

Adipocytes↗
PubMed2005

Expression pattern of the activating protein-1 family of transcription factors in gestational trophoblastic lesions.

The human placenta is an endocrine tissue with a unique capacity for rapid, but tightly controlled, proliferation and invasion. Gestational trophoblastic diseases (GTDs) are placental pathologies with endocrine activity and partially malignant potential and include hydatidiform moles, placental site nodules, and tumors such as placental site trophoblastic tumor and choriocarcinomas. The activating protein-1 (AP-1) family of transcription factors is composed of the cellular homologs of the Jun and Fos oncoproteins, which are immediately involved in cellular proliferation, differentiation, and invasion processes and in the regulation of endocrine genes. The expression pattern of the AP-1 family in the normal human placenta has been recently described, where most of the factors were found in the extravillous (invasive) trophoblast. Their systematic expression in GTD has not been studied thus far. For this reason in this study, we investigated the expression pattern of the AP-1 family in GTDs and compared it with the expression in normal placenta using immunohistochemistry with specific polyclonal antibodies against all members of the AP-1 family (JunB, JunD, c-Jun, c-Fos, FosB, Fra-1, Fra-2). Immunohistochemistry was performed on normal human placentas (positive control) and on 28 cases of GTD including 7 choriocarcinomas and 21 hydatidiform moles. In the normal placenta and in hydatidiform molar samples, most AP-1 factors (especially c-Jun, JunD, and Fra2) were expressed in the intermediate (extravillous) trophoblast. In addition, in molar lesions, strong expression was found in trophoblasts proliferating from the surface of villi. There was only a weak expression of JunB and Fra2 in small fractions of villous cyto- and syncytiotrophoblast nuclei. In choriocarcinomas, there was a strong expression for c-Jun, JunD, Fra1, and Fra2. The specific localization to extravillous trophoblasts and their expression pattern in GTDs indicate that the AP-1 family of transcription factors might be implicated in regulating proliferation and invasion of trophoblasts and play a role in the pathogenesis of GTDs.

Female↗
PubMed1997

Evaluation of trophoblast HLA-G antigen with a specific monoclonal antibody.

A monoclonal antibody to HLA-G has been generated by immunizing HLA-A2.1/human beta 2-microglobulin (beta 2 m) double transgenic mice with murine L cells transfected with both human beta 2 m and HLA-G. This monoclonal antibody, designated as G233, has been found not to cross-react with other HLA class I antigens when tested on numerous cell lines by flow cytometry. With immunohistology, all populations of extravillous trophoblast (cell columns, interstitial trophoblast, endovascular trophoblast, placental bed giant cells) were stained. An extensive range of adult and fetal tissues was also tested but none reacted with monoclonal antibody G233, including those previously reported to express HLA-G mRNA, indicating that the protein has a highly restricted distribution. Failure to detect HLA-G in the fetal thymus raises the question as to how T-cell tolerance to this antigen is induced. Immunoprecipitation of trophoblast surface proteins with monoclonal antibody G233 revealed a heavy chain of 39 kDa and a light chain of 12 kDa, indicating that HLA-G expressed on the surface of trophoblast is complexed with beta 2 m. However, sequential immunoprecipitation with monoclonal antibody W6/32 followed by monoclonal antibody G233 continued to detect a residual band of 39 kDa, suggesting that trophoblast surface HLA-G may also occur as free heavy chains not associated with beta 2 m. Immunoprecipitation followed by two dimensional gel electrophoresis showed that monoclonal antibody G233 recognizes several isoforms of HLA-G from trophoblast similar to the characteristic spot array previously described for HLA-G. This monoclonal antibody G233 will be highly useful in future experiments to elucidate the function of HLA-G.

Adult↗
PubMed1983

Trophoblast alterations in the placental bed in relation to physiological changes in spiral arteries.

Ninety-three placental bed biopsies containing a segment of a spiral artery at the level of the decidual-myometrial junction (53 with and 40 without physiological changes) were histologically investigated for depth of trophoblastic penetration of the uterine wall, formation of trophoblastic multinucleated giant cells and the enzyme histochemical characteristics of the interstitial (stromal) and vascular (intramural) trophoblast. The depth of trophoblastic penetration was not related to the presence or absence of the physiological changes. Conversely, in the absence of physiological changes, a significant accumulation of multinucleated giant cells at the decidual-myometrial junction was found before 36 weeks of gestation. The enzyme histochemical characteristics of the placental bed trophoblast suggest a stromal migration of trophoblast to the proximal (decidual-myometrial) part of the spiral artery whereas the distal part might be invaded by intraluminal (upstream) invasion. The hypothesis is put forward that in the absence of physiological changes a disturbed stromal migration is caused by intrinsic (trophoblastic) or extrinsic (interstitial of vascular) factors expressed by the augmentation of the multinucleated cells at the decidual-myometrial junction.

Female↗
PubMed1991

Trophoblast deportation in pre-eclamptic pregnancy.

OBJECTIVES: To examine the deportation of trophoblast cells into the maternal blood in pre-eclamptic (gestational proteinuric hypertension) and normal pregnancy. DESIGN: The monoclonal anti-cytokeratin antibody JMB2 was used in the APAAP technique to label trophoblast cells in cell smears of uterine vein blood obtained at caesarean section. SUBJECTS: 10 women with proteinuric pre-eclampsia requiring caesarean section, 10 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia and five control women who had never been pregnant. RESULTS: Three populations of trophoblast cells were identified; two mononuclear cytotrophoblast types with diameters varying from 11-14 microns and 19-25 microns respectively, and multinucleated syncytiotrophoblast cells varying in size from 23-88 microns. Women with pre-eclampsia had more trophoblast cells in uterine vein blood than were found in pregnant women without pre-eclampsia. There was no correlation between the numbers of trophoblast cells and the stage of gestation or severity of the pre-eclampsia, although an acute maternal or fetal event necessitating delivery was associated with increased deportation of trophoblast. Mononuclear cytotrophoblast cells were detected in the peripheral blood of only 1 of 5 pre-eclamptic patients, despite their presence in the uterine vein blood of all 5 women. CONCLUSIONS: Trophoblast deportation is increased in pre-eclamptic pregnancy, with both cytotrophoblast and syncytiotrophoblast present in the uterine vein blood, but there is no correlation with the severity of the disease. In some cases cytotrophoblast may also enter the peripheral circulation.

Antibodies, Monoclonal↗
PubMed1996

Non-invasive prenatal diagnosis by isolation of both trophoblasts and fetal nucleated red blood cells from the peripheral blood of pregnant women.

OBJECTIVE: To isolate fetal trophoblasts and nucleated red blood cells from the peripheral blood of pregnant women. DESIGN: Trophoblasts were isolated from whole blood of women in the first trimester of pregnancy by a specific monoclonal antibody, 340. Nucleated red blood cells were isolated by separating whole blood on a triple gradient, staining with ferromagnetic particles coated with an antitransferrin monoclonal antibody and separated on a mini magnetic activated cell sorting (MACS) column. Sorted cells were sexed using a nested polymerase chain reaction for a specific sequence on the Y chromosome and the sex was confirmed by karyotyping of chorionic villus samples. PARTICIPANTS: Patients between 10 and 14 weeks of pregnancy who were undergoing elective chorionic villus sampling for the detection of fetal aneuploidies. MAIN OUTCOME MEASURE: Fetal sex determined by polymerase chain reaction on fetal cells sorted from maternal blood. RESULTS: When both trophoblasts and nucleated red blood cells were sorted, fetal sex was correctly predicted in 12/13 cases (92%), which included correct diagnosis of five of six male pregnancies. More importantly the two techniques were complementary, with only one male pregnancy being diagnosed on both trophoblasts and nucleated red blood cells, two being detected only with trophoblasts and two on nucleated red blood cells alone. No false positives (male signal from a female pregnancy) were diagnosed with either trophoblasts or nucleated red blood cells even with the highly sensitive nested polymerase chain reaction technique, which is very prone to contamination. This study also shows that it is possible to isolate both trophoblasts and nucleated red blood cells from the same sample of maternal blood. CONCLUSION: Fetal cells can be isolated from maternal blood at around 10 weeks of pregnancy.

Aneuploidy↗
PubMedDate not supplied

Allo-antigenicity of trophoblast cells.

Trophoblast cells of the placenta represent the frontier of the conceptus at the feto-maternal interface, exposed to the maternal immune system. The presence or the absence of major histocompatibility (MHC) antigens on trophoblast cells, thus, is a key determinant of immune interactions between the mother and the allogeneic fetus during pregnancy. This article critically reviews the studies of the alloantigenic status of murine and human trophoblast cells, including the published data in the mouse and unpublished data in the human in the authors' own laboratory. It is shown that, in both these species, a significant proportion of trophoblast cells express Class 1 but not Class 2 MHC antigens in a manner directly accessible to the maternal immune system. However, the lack of immunogenicity of semiallogeneic trophoblast cells can not solely be explained on the basis of the absence of Class 2 molecules, despite the presence of Class 1 molecules. It is proposed either that the Class 1 MHC antigens on the trophoblast cells are presented in a nonimmunogenic manner to the maternal T cells or else that certain cells at the feto-maternal interface (eg, fetally derived trophoblast cells, maternally derived lymphoid cells, or decidual cells) elaborate potent immunosuppressor molecules capable of abrogating T cell alloreactivity.

Animals↗
PubMed1996

Cytokine expression by models of human trophoblast as assessed by a semiquantitative reverse transcription-polymerase chain reaction technique.

PROBLEM: Cytokines form an important communication network between the mother and fetus. Defining the significance of these factors requires an understanding of their constitutive expression by maternal and fetal tissues. This study examines cytokine expression by human trophoblast. METHODS: A reverse transcription polymerase chain reaction (RT-PCR) technique was used to assess cytokine expression by choriocarcinoma cells (BeWo, JEG-3, and JAR) and term trophoblast. Placental digests were enriched for trophoblast by immunoaffinity (CD-9) columns. RESULTS: Interleukin (IL)-1, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were weakly expressed or absent in the choriocarcinoma cells. In contrast, these cytokines were expressed by term trophoblast. IL-6, IL-10, IFN-alpha, IFN-beta, and granulocyte macrophage-colony stimulating factor (GM-CSF) mRNA were detected in all trophoblast cells, except for a paucity of IL-10 expression by JEG-3 cells. CONCLUSIONS: Human choriocarcinoma cells and term trophoblast express cytokines that may regulate critical reproductive events. Expression of inflammatory cytokines such as IL-1, TNF-alpha, and IFN-gamma by term trophoblast could trigger labor or be a consequence of labor-associated events.

Cell Line↗
PubMed1997

Expression of cell adhesion molecules in the extravillous trophoblast is altered in IUGR.

PROBLEM: The invasion of trophoblast cells into the uterine wall and its arterial system is essential for the normal development of pregnancy. Cell adhesion molecules (CAM), such as the immunoglobulin superfamily and integrins, play a crucial role in a number of immunological reactions and in the invasion of the human trophoblast. Intrauterine growth restriction (IUGR) has been associated with abnormal trophoblast invasion. Therefore, the expression of CAM in the extravillous trophoblast of pregnancies complicated by IUGR might be different from normal pregnancies. METHOD OF STUDY: Normal (n = 21) and IUGR (n = 19) placentas were collected and stored at -70 degrees C. Immunohistochemistry (avidin-biotin complex peroxidase-doublestaining) of frozen tissue sections was performed using antibodies specific for the immunoglobulin superfamily vascular adhesion molecule-1 (VCAM-1; CD 106), intercellular adhesion molecule (ICAM-1) (CD 54), ICAM-2 (CD 102), ICAM-3 (CD 50), the integrins alpha 2 beta 1, alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1 and cytokeratin. The percentage of immunopositive extravillous trophoblast cells (EVT) and the intensity of the immunoreactivity for the various CAM and integrin antibodies was assessed. RESULTS: In IUGR placentas, there was less expression of VCAM-1 (CD 106), alpha 2 beta 1, alpha 3 beta 1, and alpha 5 beta 1 (P < 0.05) in the extravillous trophoblast than in normal pregnancies. Finally we observed for the first time that ICAM-3 was expressed on EVT and that its expression was markedly up-regulated in the EVT or IUGR placentas. No differences were found for ICAM-1 (CD 54), ICAM-2 (CD 102), alpha 4 beta 1 and alpha 6 beta 1. CONCLUSION: Our data show that there are significant differences in the expression of cell adhesion molecules of the extravillous trophoblast from IUGR and normal pregnancies. These differences might reflect changes in the immunological reactions and cell-cell interactions between mother and the developing fetus which could interfere with fetal growth.

Antigens, CD↗
PubMed1998

MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression.

PROBLEM: Major histocompatibility complex (MHC) class II molecule expression is specifically suppressed on fetal trophoblasts, even in response to interferon (IFN)-gamma, a potent inducer of MHC class II genes. The suppression of class II induction has been suggested to play a role in preventing rejection of the fetal allograft. The mechanism of this suppression is unknown. METHOD OF STUDY: Human trophoblast cell lines were examined for expression of MHC class II transcription factors and for activity of the IFN-gamma signaling pathway. Additionally, trophoblast cells were transfected with a vector expressing the class II transactivator, CIITA, and assayed for class II expression. RESULTS: The MHC class II transcription factors RFX and X2BP and the IFN-gamma signaling pathway components are expressed constitutively and are functional in trophoblasts. However, CIITA expression was absent in trophoblasts and could not be induced by IFN-gamma. Transfection of CIITA into trophoblast cells resulted in derepression of class II gene expression. CONCLUSIONS: The lack of induction of MHC class II genes in response to IFN-gamma in trophoblast cells is caused neither by the absence of factors that bind class II promoters, nor by a lesion in the IFN-gamma signaling pathway, but results from a specific inhibition of the CIITA gene.

Cell Line↗