Basal Trophoblast Research Articles

Antiphospholipid Antibodies Inhibit Trophoblast Toll-Like Receptor and Inflammasome Negative Regulators.

Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications associated with poor placentation and placental inflammation. Although these antibodies are heterogeneous, some anti-β2 -glycoprotein I (anti-β2 GPI) antibodies can activate Toll-like receptor 4 (TLR-4) and NLRP3 in human first-trimester trophoblasts. The objective of this study was to determine the role of negative regulators of TLR and inflammasome function in aPL-induced trophoblast inflammation. Human trophoblasts were not treated or were treated with anti-β2 GPI aPL or control IgG in the presence or absence of the common TAM (TYRO3, AXL, and Mer tyrosine kinase [MERTK]) receptor ligand growth arrest-specific protein 6 (GAS6) or the autophagy-inducer rapamycin. The expression and function of the TAM receptor pathway and autophagy were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Antiphospholipid antibody-induced trophoblast inflammation was measured by qRT-PCR, activity assays, and ELISA. Anti-β2 GPI aPL inhibited trophoblast TAM receptor function by reducing cellular expression of the receptor tyrosine kinases AXL and MERTK and the ligand GAS6. The addition of GAS6 blocked the effects of aPL on the TLR-4-mediated interleukin-8 (IL-8) response. However, the NLRP3 inflammasome-mediated IL-1β response was not affected by GAS6, suggesting that another regulatory pathway was involved. Indeed, anti-β2 GPI aPL inhibited basal trophoblast autophagy, and reversing this with rapamycin inhibited aPL-induced inflammasome function and IL-1β secretion. Basal TAM receptor function and autophagy may serve to inhibit trophoblast TLR and inflammasome function, respectively. Impairment of TAM receptor signaling and autophagy by anti-β2 GPI aPL may allow subsequent TLR and inflammasome activity, leading to a robust inflammatory response.

Polarity and the placenta.

Placental development requires a transcription factor, grainyhead-like 2 (GRHL2), which is expressed highly in cells that help generate the branched morphology of the organ, according to a new study in mouse and human tissue [1]. Grainyhead-like transcription factors are involved in epithelial development in several species—for instance, in formation of epithelial barriers. Katharina Walentin et al. were intrigued to find that GRHL2 is also expressed at high levels in mouse basal chorionic trophoblast (BCT) cells. Those cells form an epithelial cell-like layer during early embryogenesis, with their basement membranes abutting the allantoic mesoderm, which is derived from the embryo proper. As embryogenesis proceeds, this layer of BCT cells undergoes branching in coordination with the branching of endothelial cells, and the result is proper establishment of the maternalfetal interface. To find out more, Walentin et al. generated mice deficient in Grhl2 and found major defects in BCT cell polarity and basement membrane integrity. The mice also had severe disruptions in placental branching initiated by the BCT cell layer. Molecular analyses suggested that GRHL2 positively regulates a suite of genes, including those previously implicated in placental development and epithelial morphogenesis. One of these genes is serine protease inhibitor Kunitz type 1 (Spint1), and mice deficient in Spint1 are very similar to those deficient in Grhl2. Spint1 is known to positively regulate Cdh1, encoding the cell adhesion protein E-Cadherin. The findings may have implications for human disorders such as pre-eclampsia and fetal growth retardation, which can often be traced to placental defects. The researchers found that human orthologs of GRHL2 were expressed highly in human placental cells analogous to BCT cells—human villous cytotrophoblasts. Moreover, gene targets of GRHL2 identified in previous studies showed co-regulation in human placental tissue, in particular SPINT1.

Aspirin and Heparin Effect on Basal and Antiphospholipid Antibody Modulation of Trophoblast Function

Low molecular weight (LMW) heparin, with or without aspirin (acetylsalicylic acid [ASA]), is used to prevent complications in antiphospholipid syndrome in pregnancy. Our objective was to elucidate the actions of low-dose LMW heparin and ASA on basal and antiphospholipid antibody-induced modulation of trophoblast function. The human first-trimester trophoblast cell line (HTR-8) was treated with or without antiphospholipid antibody in the presence of no medication, low-dose LMW heparin, low-dose ASA, or combination therapy. Interleukin (IL)-6, IL-8, IL-1β, growth-regulated oncogene-α, vascular endothelial growth factor (VEGF), placental growth factor, soluble FMS-like tyrosine kinase-1, and soluble endoglin were measured in the supernatant. Cell migration was performed using a two-chamber assay. Low molecular weight heparin improved basal trophoblast migration and induced potent increases in growth-regulated oncogene-α and soluble FMS-like tyrosine kinase-1. Aspirin did not affect basal function. Combined therapy promoted migration but did not reverse the LMW heparin-induced soluble FMS-like tyrosine kinase-1 effect. Antiphospholipid antibody increased IL-8, IL-1β, growth-regulated oncogene-alpha, VEGF, placental growth factor, and soluble endoglin secretion, while decreasing cell migration and IL-6 and soluble FMS-like tyrosine kinase-1 secretion. The antiphospholipid antibody-induced cytokine changes were best reversed with LMW heparin, with partial reversal of IL-8 and IL-1β upregulation. The antiphospholipid antibody-induced angiogenic changes were worsened by LMW heparin, with increased soluble FMS-like tyrosine kinase-1 secretion. The therapies did not reverse antiphospholipid antibody-induced decrease in migration. In the absence of antiphospholipid antibodies, LMW heparin induces potentially detrimental proinflammatory and antiangiogenic profile in the trophoblast. In the presence of antiphospholipid antibodies, single-agent LMW heparin may be the optimal therapy to counter trophoblast inflammation, but also induces an antiangiogenic response. These findings may explain the inability of current therapies to consistently prevent adverse outcomes.

The effect of probenecid and MK-571 on the feto-maternal transfer of saquinavir in dually perfused human term placenta

Human placenta, particularly the blood–placenta barrier, with various transporters has crucial role to protect the fetus and, on the other hand, to facilitate movement of compounds towards the fetal circulation. This study aimed to characterize the role of basal transporters of the syncytiotrophoblast, which appear to be yet less studied, in the fetal-to-maternal transfer of saquinavir by use of dually perfused human placentas. A dual perfusion of human placenta was performed to study effect of MK-571 and probenecid, inhibitors of the MRP1 and OATP transporters, expressed in the basal trophoblast membrane, on the transfer of saquinavir. The fetal-to-maternal placental transfer of saquinavir in the control group as measured by TPT AUC% (absolute fraction of the dose crossing placenta) was 14.0%, which is 73% less than the transfer of the freely diffusible antipyrine. The two inhibitors, MK-571 and probenecid caused a non-significant ( P = 0.34 for ANOVA) reduction of 43% and 24%, respectively, in the mean amount of saquinavir transferred from the fetal to the maternal side. MK-571 also somewhat (by 31%) reduced the TPT AUC% of antipyrine, but this finding did not reach statistical significance ( P = 0.25). Neither of the employed inhibitors had an effect on the placental transfer index of saquinavir transfer ( P = 0.77). The present results indicated lack of significant effect by MK-571 and probenecid on the fetal-to-maternal transfer of saquinavir and suggest that MRP1 and, possibly, OATP2B1 do not play a significant role in the fetal-to-maternal transfer of saquinavir.

Expression and function of a new angiogenic factor AA98 target molecule at the maternal-embryonic boundary of rhesus monkey

The target molecule of monoclonal antibody AA98 (AA for short) is a new vascular endothelial cell related factor and plays a role in angiogenesis as indicated by the previous data. To investigate its role in angiogenesis and placentation in primate, we examined its expression in the implantation sites on D17, 19, 28 and 34 of gestation in rhesus monkey by immunohistochemistry and Western immunoblot. Western blot analysis showed that the primary antibody used in this study was specific for its epitope. AA protein was mainly expressed in small blood vessels and in some cytotrophoblast cells. The AA staining was found mainly in the endothelial cells and vascular small muscle. This observation supported the AA's role in angiogenesis. AA was spatio-temporarily expressed in cytotrophoblasts: weak in proliferating trophoblast within cell column and endovascular trophoblast, strong in trophoblastic subpopulation within the basal plate and vascular trophoblast; AA staining within the basal plate was down-regulated during early placentation. The shift of AA98 expression in extravillous trophoblasts suggestes a role of this new factor during the course of cytotrophoblast metastasis and spiral artery remodeling. The spatio-temporarily expression indicats that AA98 could be also used as a trophoblast cellular marker to characterize the acquisition of a vascular endothelial and invasive phenotype.

Hepatocyte Growth Factor Induced Human Trophoblast Motility Involves Phosphatidylinositol-3-Kinase, Mitogen-Activated Protein Kinase, and Inducible Nitric Oxide Synthase

Hepatocyte growth factor (HGF) increases human trophoblast motility and invasion, an effect which is abrogated when inducible nitric oxide synthase (iNOS) is inhibited. In this study we have investigated the pathways involved in the regulation of trophoblast motility. Both basal and HGF-stimulated motility of the extravillous trophoblast cell line, SGHPL-4, were inhibited in a dose-dependent manner by the phosphatidylinositol-3-kinase (PI3-kinase) inhibitor, LY294002. HGF-stimulated iNOS expression was also inhibited by LY294002 and direct activation of PI3-kinase, using the peptide 740Y-P, led to an increase in iNOS expression and cell motility. Pretreatment with rapamycin, which acts at a point distal to PI3-kinase activation, also inhibited basal and HGF-stimulated motility. Inhibition of the p42/p44 mitogen activated protein kinase (MAPK) pathway but not the p38 MAPK pathway had significant inhibitory effects on HGF-stimulated but not basal trophoblast motility. Inhibition of p42/p44 MAPK also inhibited HGF-induced iNOS expression. This data demonstrate that the PI3-kinase signaling pathway is involved in basal trophoblast motility and that both MAPK and PI3-kinase signaling pathways are important in HGF-stimulated motility and iNOS expression.

Localization and possible role of membrane type metallo-proteinase and tissue inhibitors of metalloproteinase-1 in early stages of placentation

Human placental tissues from the first and second trimesters of gestation have been investigated using riboprobe in situ hybridisation of mRNA sequences coding for membrane type metalloproteinase (MT-1-MMP) and tissue inhibitors of metalloproteinase-1 (TIMP-1). Results show that (i) both mRNAs express at a relatively high level in the chorion laeve trophoblast cells and the adjacent decidual cells of fetal membrane; (ii) the most abundant expression of the two mRNAs was found in the extravillous trophoblast between Rohrs and Nitabuch striae of basal plate, trophoblast shell and gland cells of the decidua; (iii) isolated or small groups of cytotrophoblast cells in the chorionic villi and in the cells lining arterioles in decidua and stem villi also expressed both MT-1-MMP and TIMP-1 at defferent extents. The data suggest that the coordinated expression of the MT-MMP and its inhibitor TIMP in defferent cells of the placental tissue may play an essential role in trophoblast invasion and angiogenesis related to placentation in the first two trimesters of gestation. They may also have an ability to effect separation of fetal from material tissue at a favorable junctional site during parturition.

Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide.

1. The expression of hepatocyte growth factor (HGF) is essential for normal placental development although its function is unknown. In this study we examined the effect of HGF on trophoblast cell motility and invasion of fibrin gels and investigated the possible role of nitric oxide (NO) in this process. 2. The human extravillous trophoblast cell line SGHPL-4 express both the constitutive and inducible isoforms of nitric oxide synthase (NOS). 3. HGF significantly stimulates cell motility in monolayer culture, the invasion of fibrin gels and the production of guanosine 3':5'-cyclic monophosphate (cyclic GMP). 4. Invasion, motility and cyclic GMP production were inhibited by Ng-monomethyl-L-arginine (L-NMMA). 5. Cell motility was also significantly inhibited by the inducible NOS specific inhibitor 1400 W. 6. Neither 8 Br-cyclic GMP nor the NO donor spermine-NO had any significant effect on basal trophoblast cell motility. 7. The data presented in this study demonstrate a direct effect of trophoblast-derived NO synthesis on trophoblast cell function and support the idea that HGF is involved in the regulation of trophoblast invasion through mechanisms that involve the production of NO. However neither exogenous NO nor activation of cyclic GMP-dependent pathways alone are sufficient to stimulate trophoblast cell motility.

Seminal fluid and the expression of MHC class I antigens in the placenta of the rat.

To determine whether seminal fluid influences the expression of MHC class I antigens on the surface of basal trophoblast cells in the placenta of the rat. Transfer of DA x DA embryos into a WF (allogeneic) or DA (syngeneic) recipient made pseudopregnant by hormonal treatment followed by mating with a vasectomized male (seminal fluid) or by mechanical stimulation (no seminal fluid). Antigen expression was determined by electron microscopic immunocytochemistry using the appropriate gold-labeled monoclonal antibodies. Seminal fluid did not affect the expression of MHC class I antigens on the surface of the basal trophoblast in either allogeneic or syngeneic matings. The suppression of the expression of paternal class I antigens on the surface of the basal trophoblast cells in allogeneic pregnancies most likely occurs at the genome level shortly after fertilization.

Regulation of placental metabolism by glucose supply

Glucose is supplied to the placenta and fetus from the maternal plasma according to concentration-dependent mechanisms exhibiting saturation kinetics that are mediated by facilitative transporter proteins on both the maternal-facing microvillus and fetal-facing basal trophoblast membranes. Placental glucose transport to the fetus requires a net maternal-to-fetal plasma glucose concentration gradient that is determined by placental as well as fetal glucose consumption. Fetal plasma glucose concentration, independent of maternal glucose concentration, regulates the partition of placental glucose uptake into transfer to the fetus and consumption by the placenta. Placental transport capacity increases with advancing gestation, probably by an increased number of transporter proteins as surface area increases. Placental glucose consumption contributes to most or all of placental lactate and fructose production and other less well defined non-oxidative pathways of carbon metabolism. Placental glucose consumption accounts for at least 50% of placental oxygen consumption which remains independent of short-term or long-term changes in placental glucose supply, thus requiring varying amounts of other carbon substrates. Placental glucose supply, therefore, plays a key role in regulating placental glucose metabolism and placental carbon balance, and interacts reciprocally with other carbon substrates to maintain placental oxidative metabolism.

Major Histocompatibility Complex Class I Antigens Expressed on Rat Trophoblast Cells

There is controversy about the size of the major histocompatibility complex antigens of trophoblast cells from placenta. There are some reports that the heavy chains of these molecules are smaller (39-43 kd) than those of the classical class I antigens (45-46 kd), while there are others which show that both the light and the heavy forms of class I antigens occur in the trophoblast cells. In order to investigate this problem, we studied the classical class I antigen (RT1.Aa) and the pregnancy-associated class I antigen (Pa) of the rat from 125I-labeled basal trophoblast cells, isolated from the placenta of WF females pregnant by DA males, using very mild conditions. These antigens were compared with those of the syngeneic (DA x DA) trophoblast cells or paternal (DA) lymphocytes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both the Aa and Pa antigens, precipitated from the two trophoblast preparations, showed a heavy chain of 46 kd associated with a 12 kd beta 2-microglobulin component, as did the same molecules precipitated from the lymphocytes. Heavy chains in the range of 39-43 kd could not be detected in any of the samples. The results suggest that the smaller molecular weight heavy chains are methodological artifacts and could arise from loss of a glycan(s) during isolation.

Gene imprinting and major histocompatibility complex class I antigen expression in the rat placenta.

Ultrastructural immunocytochemical studies of the expression of major histocompatibility complex class I antigens in the placentas of inbred rats were performed using placentas derived from natural matings and from embryo transfers into females made pseudopregnant by mechanical stimulation. The studies utilized the WF (u) and DA (a) strains and monoclonal antibodies to all of the class I antigens involved. All four mating combinations of the two strains showed that only paternal antigens were expressed in the placenta and that they were limited to the basal trophoblast. This conclusion was confirmed using embryo transfer experiments. In allogeneic natural matings, the allele-specific class I transplantation antigens were not expressed on the membrane of the basal trophoblast but they were expressed in embryo transfers involving embryos of the same genotype. In both types of pregnancies, the pregnancy-associated (Pa) antigen was present on the membrane of the basal trophoblast. The antibody response to DA X DA and to WF X DA embryos transferred into pseudopregnant WF females was against the allele-specific RT1.Aa antigen and the Pa antigen, whereas the antibody response to the heterozygous embryo in the natural WF (female) X DA (male) mating was against the Pa antigen only. These results are consistent with the hypothesis that the suppression of the expression of the allele-specific major histocompatibility complex class I antigens occurs shortly after fertilization and that it requires the uterine environment of a natural mating.

A unique antigen, RT11, in the placenta of the rat.

In the course of exploring the antibody response in the unsensitized WF (u) female pregnant by a DA (a) male, we prepared a hybridoma that secreted an antibody (mAb 213) that was specific to the a haplotype but identified an antigen different from Pa. This antigen was designated RT11. It is present from the twelfth day of gestation on the collagen fibers of the placenta and of all organs in fetal and adult rats. It is particularly prominent on red blood cells; in the yolk sac epithelium; in the walls of the endodermal sinus, blood vessels and bronchioles; and in capsules and trabeculae. A very small amount is present on DA lymphocytes, since 17-20% of them react with mAb 213 by cytofluorimetry. The RT11 antigen is absent from the basal and labyrinthine trophoblast cells, from the parenchymal cells of all organs, and from T and B cells. This distribution pattern is completely different from that of the Aa and Pa antigens. Inhibition and absorption studies showed that RT11 is not an integral part of the collagen molecule. The SDS-PAGE analysis of the immunoprecipitates of RT11 from radioiodinated whole-membrane extracts of red blood cells and from the glycoprotein fraction thereof showed that it is an unglycosylated protein of molecular weight 29,000. The evidence to date suggests that RT11 is a blood group antigen. Studies on the genetic control of the expression of RT11 were undertaken to determine whether a gene linked to the MHC was involved and whether the control mechanism was unigenic or polygenic. Backcrosses generated using inbred strains--(DA x BN)F1 x DA-- and using complementary congenic strains--(DA.1N x BN.1A) F1 x BN.1A--showed that the expression of RT11 was under polygenic control, and that both an MHC-linked gene (1.2 cM from RT1.Aa) and genes not linked to the MHC are involved. By contrast, the expression of the Pa antigen is under the control of an MHC gene only.

Immunohistochemical study of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) in the human and cynomolgus monkey placenta, umbilical cord and decidua

Tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) were studied immunohistochemically by the avidin-biotin immunoperoxidase technique in human and cynomolgus monkey placentae, membranes, umbilical cords and decidua. In early human placentae, TPA was localized mainly in the cell membranes of villous syncytio- and cyto-trophoblast. The cytoplasm of those trophoblastic cells were weakly stained with TPA. The membrane of basal chorionic trophoblast cells was strongly stained with TPA and the cytoplasm stained weakly. In early cynomolgus placentae, similar immunostaining results were obtained. However, the positive stainings for TPA was more marked in the cytoplasm of villous syncytiotrophoblast and basal chorionic trophoblast, and less marked in the cell membrane of villous cytotrophoblast. In early human and cynomolgus placentae, CA125 was not demonstrated immunohistochemically in the villi and basal chorion. In human and cynomolgus term placentae, the villous syncytiotrophoblast and basal and reflected chorionic trophoblast showed similar immunostaining as the early placentae. In addition, TPA was found in the amniotic epithelium in both sorts of placentae. TPA was not detected immunohistochemically in the umbilical cord and decidual cells. While weakly positive stains for CA125 were observed in decidual cells, CA125 was localized mainly in the membrane and cytoplasm of amniotic epithelium in both human and cynomolgus term placentae. TPA and CA125 are thus oncoplacental antigens and the monkey could serve as a model for their investigation.

Isolation and characterization of rat trophoblast cells.

Previous immunohistochemical studies of the rat placenta using specific alloantisera and/or monoclonal antibodies showed that the basal zone trophoblasts stained for Pa and Aa class I major histocompatibility complex (MHC) antigens and for the human SP1-related antigen. In an effort to isolate the basal zone trophoblast cells from the rat placenta, we used these markers to assess the degree of purification of the cells separated by density gradient centrifugation using either Ficoll-Hypaque or Percoll as the gradient medium. The cells were put either on the top or at the bottom of discontinuous density gradients in the range of 1.005-1.10 g/ml. The cell separation profiles for the two media were different. With Percoll, most of the trophoblast cells (80-95%) were collected at the density gradients 1.04/1.06 and 1.06/1.08, whereas with Ficoll-Hypaque, these gradients separated only a small fraction (4-23%) of the trophoblast cells, and most of them pelleted at the bottom of the tube. The trophoblast cells separated by Ficoll-Hypaque, however, showed fewer contaminant cells than those separated by the Percoll gradients.

Differential expression of MHC class I antigens on the placenta of the rat. A mechanism for the survival of the fetal allograft.

In some mating combinations in rats, there is a maternal antibody response to the maternal antigenic components of the placenta without any previous immunization of the mother. The highest response occurs in the WF (u) female mated to the DA (a) male, and it is against a unique MHC-encoded class I antigen, the Pa antigen, and not against the major allele-specific transplantation antigen of the DA strain, RT1.Aa. The development of mAbs to the Pa and Aa antigens allowed us to localize these antigens on the placenta and to explore the reason for the differential antibody response to them using immunohistochemical and biochemical techniques. Both antibodies reacted with the WF X DA placenta and stained the endovascular and interstitial trophoblast of the decidua, the basal trophoblast, Reichert's membrane, and the yolk sac epithelium, but they did not stain the labyrinthine trophoblast. Blocking studies showed that each antibody reacted with a separate molecule in the placenta. Anti-class II mAbs reactive with the a or u haplotype did not stain the WF X DA, DA X DA, or WF X WF placenta; hence, there are no class II antigens in the placenta. Electron microscopic studies of the semiallogeneic WF X DA placenta using the immunogold technique with both single- and double-labeling showed that only the Pa antigen was expressed on the surface of the basal trophoblast, but that both the Pa and Aa antigens were in the cytoplasm of these cells; neither antigen was found in the labyrinthine trophoblast. By contrast, the placenta from the syngeneic DA X DA mating expressed both the Pa and Aa antigens on the surface of the basal trophoblast as well as in the cytoplasm; neither antigen was found in the labyrinthine trophoblast. These observations were quantified morphometrically using electron photomicrographs of single-labeled tissues. Both the Pa and Aa antigens isolated from the plasma membrane of lymphocytes have heavy chains of 46 kD, but those antigens isolated from the plasma membrane of basal trophoblast cells have heavy chains of 43 kD. Based on densitometric measurements of autoradiographs, the Pa/Aa ratio in the basal trophoblast membrane is 23.5, whereas it is 0.46 in lymphocyte membranes. These studies show that there is differential regulation of the expression of class I antigens on basal trophoblast cells in semiallogeneic pregnancies, but not in syngeneic pregnancies, such that the major allele-specific transplantation antigen is scarcely expressed on the surface of the basal trophoblast.(ABSTRACT TRUNCATED AT 400 WORDS)

Electron microscopic localization of the Pa and RT1.Aa antigens on the placenta of the rat

A major factor in the ability of the placenta to avoid allograft rejection is the differential expression of MHC class I antigens on its surface. Using monoclonal antibodies and the electron microscopic immunogold technique, we have demonstrated that only the pregnancy-associated (Pa) antigen, which carries a broadly shared antigenic determinant, is expressed on the placental surface in the rat, whereas the allele-specific classical transplantation antigens are not. Both types of antigens are, however, present in the cytoplasm of the basal trophoblast but completely absent from the labyrinthine trophoblast.

Distribution of Trop 3 and 4 antigens as defined by monoclonal antibodies raised against a human choriocarcinoma cell line.

The reactivities of Trop 3 and 4 monoclonal antibodies (MAbs) were studied on human term and 7-week extraembryonic membranes, adult tissues, and cell lines. Trop 3 MAb reacted with cells of chorionic villi, decidua, amniotic epithelium, and basal plate trophoblast. Trop 4 MAb reacted only with syncytiotrophoblast. On epithelium, Trop 3 MAb bound to stratified and glandular epithelium, but Trop 4 MAb reactivity was limited to basal keratinocytes. On peripheral blood mononuclear cells, Trop 3 MAb reacted with the majority of cells and Trop 4 MAb with the totality. Most cell lines were positive with both MAbs. However, one chemically induced MHC mutant was negative and another decreased its expression of Trop 3 antigen. Our results suggest Trop 3 MAb might recognize a monomorphic determinant of TLX antigens and Trop 4 is involved in cell proliferation or in cell-to-cell interaction.

Localization of the Pa antigen on the placenta of the rat.

A unique class I MHC antigen, the Pa antigen, is the major immunogenic molecule on the placenta of the rat. It carries only a widely shared public antigenic determinant, and it is located on the basal trophoblast.

The immunohistochemical localization of pregnancy-specific β1-glycoprotein in postimplantation rat trophoblast

Pregnancy-specific beta 1-glycoprotein (SP1) was identified by peroxidase-antiperoxidase (PAP) immunohistochemistry in the placenta of inbred strains of rat between 10 and 21 days of gestation. SP1 was located predominantly in basal zone trophoblast and in intravascular trophoblast of decidual vessels, but it was absent from labyrinthine trophoblast. No perivascular cells were identified by SP1 staining, but occasional clusters of interstitial trophoblast stained for SP1. The results suggest that basal and labyrinthine trophoblast are functionally different.