Trophoblast Subpopulations Research Articles

Cytokeratin 17 as an immunohistochemical marker for intramural cytotrophoblast in human first trimester uteroplacental arteries.

Trophoblast cells, as blastocyst-wall derivatives, are of epithelial origin and differentiate initially into syncytiotrophoblast and cytotrophoblast subpopulations. Cyto- and syncytiotrophoblasts are the two cell types present in the surface cell layers of placental villi. Cytotrophoblastic cells lie in contact with the basal lamina and are the proliferating stem cells that guarantee cytotrophoblast and syncytiotrophoblast persistence. Implantation and placenta formation are mainly based on these two cell types. Villous cytotrophoblasts are the stem cells for all extravillous trophoblast subpopulations, which exhibit strictly regulated invasiveness. One aspect of extravillous trophoblasts is that they invade maternal endometrial spiral arteries and dilate them in order to achieve sufficient fetal blood supply. During this process, trophoblast cells, which are located in the remodelled uteroplacental artery walls, are thus defined as intramural cytotrophoblasts. Trophoblast differentiation is accompanied and defined by alterations in, for example, the translation pattern for cytokeratin genes. In an immunohistochemical study, we have demonstrated that only intramural cytotrophoblasts, from all the trophoblast populations of the junctional zone, express cytokeratin 17. Furthermore, cell shape and vascular architecture indicate that, in human placenta, intra-arterial trophoblast cells reach their destination by migration through the endometrial interstitium with consecutive intravasation. Cytokeratin 17, in particular, can therefore be used as a specific immunohistochemical marker for the intramural trophoblast subpopulation.

Lectin histochemistry of rat placental tissues

Lectin binding of rat trophoblast subpopulations was examined at days I0, 12 and I5 of gestation. Biotinylated lectins, specific for a range of carbohydrates, were applied to paraffin wax embedded tissues. At day I0 of pregnancy, a wide and similar range of lectins reacted with ectoplacental cone and giant cells: chorionic lamina was relatively unreactive except with wheat germ agglutinin. At days 12 and I5, the range of lectins reacting with the placental labyrinth was relatively restricted. Spongiotrophoblast at day 12 showed lectin reactivity similar to that of ectoplacental cone cells but at day I5 the reaction pattern indicated loss of N-acetylgalactosamine residues in the large, glycogen-rich cells. Trophoblastic giant cells also showed wide lectin reactivity: some reacted only with cytoplasmic components whilst others showed pericellular reactivity. Varying lectin reactivity of giant cells in different regions of the placenta suggests functional differences. There was reduced lectin reactivity of endovascular trophoblast at day I5, compared with day I2 of pregnancy, which may reflect altered invasive potential associated with loss of sialic acid and N-acetylgalactosamine residues. The pattern of lectin reactivity suggests that ectoplacental cells, as well as giving rise to giant cells, may also contribute to spongiotrophoblast and to endovascular trophoblast.

Differentiation of human trophoblast cells in vitro is inhibited by dimethyl sulfoxide

The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis.Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls.This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of non–protein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization.Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-type–specific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy complication. Gene ontology analysis of the syncytiotrophoblast data highlighted the dysregulation of immune functions, morphogenesis, transport, and responses to vascular endothelial growth factor and progesterone. The invasive cytotrophoblast data provided evidence of alterations in cellular movement, which is consistent with the shallow invasion often associated with severe preeclampsia. Other dysregulated pathways included immune, lipid, oxygen, and transforming growth factor-beta responses. The data for endovascular cytotrophoblasts showed disordered metabolism, signaling, and vascular development. Additionally, the transcriptional data revealed the differential expression in severe preeclampsia of 2 classes of non-coding RNAs: long non-coding RNAs and small nucleolar RNAs. The long non-coding RNA, urothelial cancer associated 1, was the most highly up-regulated in this class. In situ hybridization confirmed severe preeclampsia-associated expression in syncytiotrophoblasts. The small nucleolar RNAs, which chemically modify RNA structure, also correlated with severe preeclampsia. Thus, we enumerated Cajal body foci, sites of small nucleolar RNA activity, in primary cytotrophoblasts that were isolated from control and severe preeclampsia placentas. In severe preeclampsia, cytotrophoblasts had approximately double the number of these foci as the control samples.A laser microdissection approach enabled the identification of novel messenger RNAs and non-coding RNAs that were misexpressed by various trophoblast subpopulations in severe preeclampsia. The results suggested new avenues of investigation, in particular, the roles of PRG2, Kell blood group determinants, and urothelial cancer associated 1 in syncytiotrophoblast diseases. Additionally, many of the newly identified dysregulated molecules might have clinical utility as biomarkers of severe preeclampsia.

Isolation and characterization of human placental trophoblast subpopulations from first-trimester chorionic villi.

A method for the simultaneous preparation of highly enriched human placental trophoblast populations (villous and extravillous) from first-trimester placental villi (5 to 12 weeks) by using sequential trypsinization, percoll gradient centrifugation, and negative selection with anti-CD9 immunomagnetic separation is described. The purification method resulted in the isolation of four distinct trophoblast populations identified on the basis of morphology and phenotyping: (i) mononuclear villous cytotrophoblast cells which, through differentiation, become committed to syncytium formation; (ii) an extravillous trophoblast population which appeared as a "crazy pavement" and, with subsequent subculturing, differentiated morphologically to mononuclear cells; (iii) an extravillous trophoblast fraction which fused to form multinucleated trophoblast giant cells; and (iv) floating intermediate extravillous trophoblast cells which fused together to form cell clumps and which further differentiated to a mononuclear anchoring intermediate extravillous trophoblast. Short-term cultures of the freshly isolated cell fractions consisted of heterogeneous trophoblasts at different differentiation stages as determined by their varied biochemical and morphological properties. All the isolated trophoblast populations expressed the cytokeratin intermediate filament and the epithelium-specific cell-cell adhesion molecule E-cadherin. The isolated villous trophoblasts in culture expressed integrins alpha 6 and beta 4 and reduced levels of beta 1 subunits, whereas the proliferating extravillous trophoblast cultures expressed alpha 1, alpha 3, and alpha 5 and high levels of beta 1 integrin subunits, vitronectin receptor (alpha V beta 3/beta 5), and major histocompatibility complex class 1 molecules. Furthermore, the isolated trophoblast populations secreted metalloproteases (such as type IV collagenases [mainly 72- and 92-kDa enzymes, i.e., gelatinases A and B]) and urokinase plasminogen activator, as evaluated by substrate gel zymography. This method of isolation should facilitate in vitro studies of trophoblast proliferation, differentiation, invasion, virus interactions, cytokenesis, and immunology.

Cytokine regulation of HLA-G expression in human trophoblast cell lines

HLA class I genes are differentially expressed among subpopulations of cells in first trimester human placentas. In this study, HLA class I protein was detected in extravillous cytotrophoblast cells by immunohistochemistry using the monoclonal antibody W6/32. In the same trophoblast subpopulation, class Ib proteins were identified with two monoclonal antibodies, 87G (anti-HLA-G) and 131 ( anti-HLA- A G ) and class Ia protein was detected with the monoclonal antibody, 4E ( anti-HLA- B C ). All of the antibodies also identified antigens on the human trophoblast-derived choriocarcinoma cell line, JEG-3. Therfore, the JEG-3 cells were used as a model system to study cytokine regulation of HLA-G in trophoblast cells. Northern blot hybridization studies showed that interferons (IFN-α, IFN-β, IFN-γ) and tumor necrosis factor-α (TNF-α) modestly enhanced steady state levels of HLA-G mRNA. Yet analysis of HLA-G protein by immunocytochemistry and flow cytometry failed to identify any changes in intracellular or membrane expression of HLA-G protein following cytokine treatment. Resistance to upregulation of HLA class I antigens was not a general feature of JEG-3 cells; IFNs enhanced expression of HLA- B C as well as HLA class I light chain, β2-microglobulin. HLA null Jar choriocarcinoma cells did not contain HLA-G mRNA or antigen and exposure to cytokines had no effect on HLA-G. The results of this study are consistent with the postulate that trophoblast cell expression of HLA-G is stringently regulated and is controlled in part by post-transcriptional mechanisms.

Trophoblast subpopulations in normal pregnancy and gestational trophoblastic tumors

Trophoblast subpopulations in normal pregnancy and gestational trophoblastic tumors

Differentiation of human trophoblast populations involves alterations in cytokeratin patterns.

Cytokeratins (CKs) are related to proliferation and differentiation of epithelial cells. Little knowledge exists about CK patterns in human trophoblast subpopulations (villous and extravillous trophoblasts). To better understand differentiation and function of trophoblast components, we studied the distribution patterns of CKs in the placenta throughout pregnancy. A panel of well-defined monoclonal antibodies against different types of cytokeratins, vimentin, and fibrin, was used on frozen and paraffin sections. CK8, 18, and 19 were expressed in all the villous and extravillous trophoblastic subsets throughout pregnancy. In the first trimester, syncytiotrophoblasts were positive for CK7 and 13 along the basal membrane. As pregnancy progressed there was an increase in intensity of the reaction product and a more diffuse positive staining of CK7 in the cytoplasm of the syncytium, with evident positivity along the apical membrane. CK13 showed similar expression as CK7, but with less intense staining along the apical membrane and less prominent staining in the cytoplasm. Villous cytotrophoblasts were also positive for CK7 and CK13. CK17 was found related to cytotrophoblastic cells in contact with or next to fibrin deposits. Extravillous cytotrophoblasts in cell islands and cell columns were positive for CK13 only in the cell layers located proximal to the villous stroma, whereas the distal and more differentiated cells were negative. CK7 was positive in all epithelial cells of cell islands and columns, but the reaction product was not present in cells deeply migrated into the decidua. Amnion was negative for anti-CK13 antibodies in the first trimester but was positive at term. CK4 and CK16 were not found in the placenta. Our study shows for the first time that the different populations of human placental trophoblast express cytokeratins in developmental, differentiative, and functional specific patterns. These findings can be useful to distinguish and classify the various trophoblastic populations and provide a foundation for studying pathological aspects of the trophoblast.

Screening for cytokine mRNA in human villous and extravillous trophoblasts using the reverse-transcriptase polymerase chain reaction (RT-PCR)

During the process of placental implantation, sessile villous trophoblast cells migrate from the villi into the decidua as isolated motile extravillous trophoblast cells. There is differential expression of the epidermal growth factor-receptor (EGF-R) and c-erbB2 proteins on villous and extravillous trophoblast populations. Using monoclonal antibodies to EGF-R and c-erbB2, we have obtained highly purified populations of villous and extravillous trophoblast by fluorescence activated cell sorting. These cells were examined by the reverse transcriptase-polymerase chain reaction (RT-PCR) using nested internal primer pairs for the following cytokines: CSF-1, GM-CSF, TNF-alpha, TGF-beta1, IFN-gamma, IL-2, LIF and also for LIF-receptor. TNF-alpha and TGF-beta 1 were present in all trophoblast populations. GM-CSF and CSF-1 were only found in some samples, with preferential expression of CSF-1 in villous populations. IFN-gamma, IL-2 and LIF mRNA were not found, although all samples contained LIF-receptor mRNA. These cytokines (CSF-1, TGF-beta, TNF-alpha and GM-CSF) are likely to influence trophoblast growth and differentiation in an autocrine manner, since their receptors are also present on trophoblast. These results illustrate a quick and simple method to analyse for the presence of cytokine and other transcripts in trophoblast subpopulations during early pregnancy.

Beta 1 integrins in third trimester human placentae: No differential expression in pathological pregnancy

Integrins are a group of cell surface receptors that play important roles in cell-cell and cell-extracellular matrix interactions. The expression of trophoblast cell surface integrin subunits changes during placental development in normal pregnancy but the functional significance is unknown. The aim of this study was to investigate the expression of β1 integrins and their extracellular matrix ligands in human placenta and membranes in normal and pathological pregnancy using an avidin-biotin-peroxidase technique. Expression of the β1 integrins was similar in all study groups. Whilst there was some heterogeneity of expression of specific integrin a chains this was not characteristic of defined subject groups, variations occurring within all groups. Two distinct trophoblast subpopulations were demonstrated in the chorion laeve according to differential expression of β1 integrins. Trophoblast immediately adjacent to maternal decidua, which expressed al rather than α2, also comprised the majority of trophoblast in the basal plate; possession of the α1, α3, α5, α6 rather than α2, α3, α5, α6 phenotype may be important in the invasive potential of trophoblast populations. The results obtained in the present study indicate that the integrin phenotypes of third trimester uteroplacental tissues are similar in normal and pathological pregnancy, including pre-eclampsia, before and after labour.

Production of interferons in human placental trophoblast subpopulations and their possible roles in pregnancy

The human cytotrophoblasts are the first fetal cells to arise during embryogenesis and are the progenitor cells to villous (noninvasive), syncytiotrophoblast (noninvasive), "intermediate" extravillous (invasive), and "anchoring" extravillous (invasive) trophoblast subpopulations. These trophoblast subpopulations were isolated from first- and third-trimester placentae and were stimulated with Sendai virus, granulocyte-macrophage colony-stimulating factors (GM-CSF), and platelet-derived growth factor (PDGF) to produce interferons (IFNs). GM-CSF and PDGF induced very low levels of IFN in first-trimester extravillous and villous trophoblast subpopulations. Highly proliferating and invasive intermediate extravillous trophoblast cultures produced five- to eightfold more IFNs than villous trophoblast cultures and two- to fivefold more IFN than the syncytiotrophoblast cultures when stimulated with Sendai virus. Syncytiotrophoblast cultures produced higher levels of IFNs (up to twofold) than villous trophoblast cultures when stimulated with the same virus. Pretreatment of first-trimester extravillous and villous trophoblast cultures with GM-CSF and PDGF followed by infection with Sendai virus resulted in greater IFN production than when the cultures were stimulated with virus alone. The levels of IFN produced were dependent on the type of trophoblast, the type of inducer, and the stage of differentiation of the trophoblasts. The purified trophoblast IFNs have potent antiviral activities when assayed on human amniotic WISH cells, and they inhibited proliferation of normal trophoblasts and trophoblast-derived malignant cells in vitro without any toxicity. Furthermore, the trophoblast IFNs activated NK cell activity and suppressed mitogen-stimulated lymphocyte proliferation at concentrations of between 10 and 1,000 IU/ml. The possible functions of the trophoblast IFNs during pregnancy are discussed with respect to human placental and fetal protection and development.

Retroviral crossreactivity of trophoblast subpopulations within human placental cell isolates

Retroviral crossreactivity of trophoblast subpopulations within human placental cell isolates

Detection of placental growth hormone variant and chorionic somatomammotropin ribonucleic acid expression in human trophoblastic neoplasms by reverse transcriptase-polymerase chain reaction.

Attempts to assess human placental GH variant (hGH-V) and chorionic somatomammotropin (hCS) RNA in choriocarcinoma cell lines have been hampered by low levels of expression and limited sensitivity of RNA blotting analysis. We examined human choriocarcinoma BeWo, JAR, and JEG-3 cell lines as well as samples of complete hydatidiform moles for expression of members of the human GH (hGH) gene family using reverse transcriptase-polymerase chain reaction. A single and common set of primers was designed and used to detect products of the hGH/hCS genes as well as distinguish processed RNA from any contaminating DNA. Transcripts from the hCS genes hCS-A and -B were distinguished from placental hGH variant (hGH-V) and hCS-like (hCS-L) gene RNA by diagnostic restriction digestion of the polymerase chain reaction products. The expected pattern of hGH/hCS RNA expression was detected in term placenta, where hCS and hGH-V/hCS-L transcripts represented approximately 95% and approximately 5% of the total hGH/hCS RNA, respectively. The level of hCS RNA varied from 22-99% of the total hGH/hCS RNA in the neoplastic trophoblast samples, and variable levels of hGH-V and hCS-L RNA were also observed. In choriocarcinoma JAR cells, hGH-V RNA represented approximately 78% of the total hGH/hCS RNA compared to approximately 22% for hCS. Further, although low hCS-L RNA levels (< 1%) were found in term placenta and two of the hydatidiform moles, hCS-L transcripts represented 11% of the total hGH/hCS RNA in a third hydatidiform mole. Finally, in contrast to the detection of variable levels of hCS-L RNA in term placenta and hydatidiform mole samples, no hCS-L transcripts were detected in the three choriocarcinoma cell lines examined. These patterns reflect either deregulated hGH/hCS gene expression in neoplastic trophoblasts or differences that accompany the process of differentiation of trophoblast subpopulations. Regardless, this suggests that the control of hGH-V and hCS-L gene expression is distinct from that of the hCS-A and hCS-B genes and raises questions about the possible involvement of hGH/hCS family members in the pathology of placental abnormalities.

Differential Lectin Binding to the Fibrinoid of Human Full-Term Placenta: Correlation with a Fibrin Antibody and the PAF-Halmi Method

Placental fibrinoid is thought to contain various glycoproteins originating from cell secretion and tissue degeneration, occasionally merged with fibrin. Information on the characteristics and derivation of the various fibrinoid components, however, is still fragmentary. Therefore, the present histochemical study on acetone-fixed placental tissue sections compared the staining pattern of FITC-conjugated lectins from Ulex europaeus (UEA-I), Bandeiraea simplicifolia (BS-I) and Lycopersicon esculentum (LEA) with the reactivity of a fibrin antibody and a modified paraldehyde-fuchsin stain. Using different color reactions, the latter histological method identified two types of fibrinoid, which correlated well with fibrin-type and matrix-type fibrinoid. Immunohistochemically, fibrin was detected at the intervillous border of the basal plate, in some inner parts and in perivillous fibrinoid. UEA-I bound to endothelial cells and partially to fibrin-type fibrinoid of villi and the basal plate, thus indicating a reaction with immured and disintegrated remnants of endothelial and blood cells. LEA stained fibrin-negative (i.e. matrix-type) fibrinoid homogeneously within the basal plate; the small reactive areas within the perivillous fibrinoid may belong to degenerating trophoblastic residues, because in villi LEA specifically reacted with the syncytiotrophoblast. BS-I heterogeneously labeled matrix-type fibrinoid deposits in the basal plate which surrounded decidual cells and subpopulations of extravillous trophoblast. In cell islands, BS-I also stained fibrinoid surrounding trophoblast cells heterogeneously. The data (1) confirm the existence of two types of placental fibrinoid, fibrin-type and matrix-type fibrinoid, (2) suggest that both types of fibrinoid contain different glycoconjugates, and (3) demonstrate the practical usefulness of the modified paraldehyde-fuchsin method for the identification of the two types of fibrinoid.

Human cytotrophoblast invasion is mediated by metalloproteinases and β1 integrins and is accompanied by changes in the expression of adhesion molecules and HLA-g

ED27 trophoblast-like cells were prepared from human chorionic villus samples obtained at 9 weeks gestation and have been grown continuously in vitro without phenotypic drift for nearly a decade. These cells express many trophoblast markers, including cytokeratin, placental alkaline phosphatase (PLAP), secretion of 17β-estradiol, and a microvillous apical surface. The ED27 cell line is a useful model system for studies of placental cell biology and has been distributed to laboratories world-wide. However, experiments to investigate their relationship to primary villous cytotrophoblast have shown that these cells do not secrete detectable amounts of human chorionic gonadotropin in culture and, when digested with trypsin, disperse into individual cells. Furthermore, immunocytochemical studies demonstrated that, unlike villous cytotrophoblasts, ED27 cells were immunoreactive with monoclonal antibodies recognizing some HLA Class I antigens. This was not HLA-G, however, as would be expected if these cells originated from extravillous cytotrophoblasts, but rather classical HLA-A, B which is thought not to be expressed by any trophoblast subpopulations. These inconsistencies prompted us to question the authenticity of the continuous cell line as it now exists. Genetic haplotype analysis using the polymerase chain reaction (PCR) revealed that ED27 was genetically identically to the HeLa cell line. Inasmuch as HeLa cells have never been grown in the laboratory (DAK), the only possible origin of HeLa cell contamination of ED27 cells was the WISH cell line, and further PCR analysis revealed that this cell line was also genetically identical to HeLa. Like ED27 cells, HeLa cells and WISH cells synthesized small amounts of estrogen and were found to express PLAP and antigens recognized by the monoclonal antibodies ED822, directed against the syncytiotrophoblast, and J1B5 directed against villous cytotrophoblast. These results point out the need for adherence to rigorous and consistent quality control measures to assure the authenticity of cell lines used as in vitro model systems.

Isolation of cell island cytotrophoblast from first trimester human placenta and characterization of NDOG5, a monoclonal antibody specific for a human trophoblast subpopulation

Isolation of cell island cytotrophoblast from first trimester human placenta and characterization of NDOG5, a monoclonal antibody specific for a human trophoblast subpopulation

Differential expression of blood-group-related carbohydrate antigens by trophoblast subpopulations

International Journal of Gynecology & ObstetricsVolume 28, Issue 4 p. 396-396 Citations from the literature experimental gynecology Differential expression of blood-group-related carbohydrate antigens by trophoblast subpopulations A King, A KingSearch for more papers by this authorYW Loke, YW LokeSearch for more papers by this author A King, A KingSearch for more papers by this authorYW Loke, YW LokeSearch for more papers by this author First published: April 1989 https://doi.org/10.1016/0020-7292(89)90643-7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume28, Issue4April 1989Pages 396-396 RelatedInformation

Differential expression of blood-group-related carbohydrate antigens by trophoblast subpopulations.

A panel of monoclonal antibodies directed at fucosylated and sialylated carbohydrates on the Type 1 and Type 2 blood group precursor chains was used in an immunohistological study of trophoblast subpopulations. Formalin-fixed paraffin-embedded sections of normal trophoblast throughout pregnancy, hydatidiform moles and gestational choriocarcinoma were examined. Sialyl-Lex was localized in extravillous trophoblast populations in normal and molar pregnancies and choriocarcinoma tumour cells. After neuraminidase treatment, Lex was identified in similar cell populations. Although Lea was identified in syncytial trophoblast cells at the maternofetal interface, no staining was seen for sialyl-Lea. Villous trophoblast did not stain with any of the monoclonal antibodies used. Our results underline the divergent differentiation of trophoblast into villous and invasive extravillous subpopulations. The analogy with tumour cells is discussed.

Major histocompatibility antigens on trophoblast and their regulation: implications in the maternal-fetal relationship.

Recent technological advances have provided methods of detecting antigens encoded by the major histocompatibility complex with greater precision, allowing the expression of such antigens on the components of the placenta to be clarified. Of specific interest is the expression of these antigens on trophoblast cells, the fetal-derived epithelial cells that confront maternal blood and tissues at the maternal-fetal interface. It is now clear that the different trophoblast subpopulations differentially express class I antigens, although none appear to express class II antigens. Class I antigens can be induced by exposure to interferons on some populations but apparently not others, suggesting that the regulation of their expression differs for subpopulations of trophoblast cells, depending on gestational stage and location. This restricted expression has important implications for maternal-fetal immune interactions during the different phases of pregnancy and perhaps also bears on physiological functions of the feto-placental unit, such as growth and differentiation.

Immunohistologic identification of trophoblast populations in early human pregnancy with the use of monoclonal antibodies

Three murine monoclonal antibodies (H315, H316, and NDOG1) have been used in a peroxidase-antiperoxidase technique on formalin-fixed paraffin-embedded tissues to identify populations of fetal trophoblast cells by their expression of membrane antigens in chorionic and decidual tissue from the first trimester of normal human pregnancy. H315 and H316 showed comparable staining of placental villous syncytiotrophoblast and cytotrophoblast and were also able to distinguish subpopulations of nonvillous trophoblast in the placental bed, including perivascular and endovascular trophoblastic cells as well as cytotrophoblastic elements within the decidua and myometrium. H315 and H316 also showed cytoplasmic staining of columnar epithelium of endometrial glands throughout the first trimester. In contrast, NDOG1 stained chorionic syncytiotrophoblast but not villous cytotrophoblast and also did not react with any cytotrophoblastic elements in the placental bed. NDOG1 distinguished these different subpopulations of trophoblast as early as 13 to 15 days after ovulation.