Judith N. Bulmer

Antigen expression by trophoblast populations in the human placenta and their possible immunobiological relevance

Antigen expression by villous and extravillous human trophoblast populations at discrete anatomical sites has been reviewed. The various different antigenic phenotypes have been highlighted using a panel of monoclonal antibodies reactive with characteristic trophoblast membrane antigens, a trophoblast-leucocyte common antigen, class I MHC antigens, epithelial cell cytokeratin and epithelial membrane markers. This approach has allowed three separate fetal trophoblast populations to be identified within term amniochorionic membranes, and also has facilitated further definition of trophoblast populations in maternal uterine tissues. Furthermore, antigenic alterations have been noted in the maternal uterine gland epithelium in pregnancy leading to the expression of a trophoblastic phenotype, thereby suggesting a mechanism of extrinsic regulation of gene expression in these tissues. The possible involvement in the immunoregulatory control of maternal responses in pregnancy of MHC-linked gene products expressed by trophoblast has been discussed.

Expression of the proliferation markers Ki67 and transferrin receptor by human trophoblast populations

Immunohistochemical techniques were used to investigate the expression of proliferation markers (Ki67 and transferrin receptor) by fetal trophoblast in normal human pregnancy. In placental villous tissue, transferrin receptor was detected not only on the apical syncytiotrophoblastic membrane but also on the proximal portion of cytotrophoblast columns, an area of high cellular proliferative activity. The majority of cells in cytotrophoblast columns and shell showed nuclear reactivity with Ki67. Villous syncytiotrophoblast was uniformly unreactive with Ki67 but a proportion of the underlying cytotrophoblast was Ki67-positive throughout pregnancy. Occasional Ki67-positive trophoblast cells were identified within chorion laeve at term. In contrast, interstitial and endovascular extravillous trophoblast in maternal uterine decidual tissue failed to label with either proliferation marker. Thus, chorionic villous cytotrophoblast and extravillous trophoblast in the chorion laeve appear to retain their proliferative capacity into late pregnancy. Cytotrophoblast columns represent a zone of cellular proliferation which may be dependent on transferrin.

Immunohistochemical Localization of Interferons in Human Placental Tissues in Normal, Ectopic, and Molar Pregnancy

ABSTRACT: Interferon (IFN)α, β, and γ have been localized in normal and pathological human pregnancy using both polyclonal and monoclonal antibodies in immunohistochemical techniques. IFNα was localized to fetal chorionic villous syncytiotrophoblast throughout normal pregnancy, as well as to extravillous trophoblast in the placental bed and chorion lave. Maternal decidual leukocytes, as well as fetal Hofbauer cells in the villous mesenchyme, also contained IFNα. IFNγ was detected in villous syncytiotrophoblast, while anti‐IFNβ showed only patchy weak reactivity with syncytiotrophoblast. Reaction patterns on ectopic pregnancy tissues were similar to those in early intrauterine pregnancy. In molar pregnancy, reactivity for IFNα, β, and γ was observed in syncytiotrophoblast. Along with their potential anti‐viral effects, placental interferons could play a role in local immunomodulation or in regulation of embryonic cell proliferation and differentiation.

Maternal and fetal cellular relationships in the human placental basal plate

Maternal and fetal cellular relationships in the normal human term placental basal plate were investigated by single and double immunohistochemical labelling techniques. Extravillous fetal trophoblast in the basal plate was uniformly reactive with markers of low-molecular-weight cytokeratins. The predominant maternal leucocyte population in the basal plate consisted of leucocyte-common-antigen-positive, class II MHC-positive macrophages, which exhibited acid phosphatase activity. Double-labelling methods highlighted the close association of these macrophages with extravillous trophoblast: they often extended processes around the fetal cells and were also observed within islands of cytotrophoblast. Other leucocytes were uncommon, although aggregates of T cells were apparent in some tissues.

Fibronectin and laminin in the early human placenta

The distribution of fibronectin and laminin was investigated in early intrauterine and ectopic tubal pregnancy using a standard immunoperoxidase technique on paraffin-embedded tissues. Localization of both fibronectin and laminin appeared identical in intrauterine and in ectopic pregnancy. Fibronectin was demonstrated in chorionic villous stroma, in the distal cytotrophoblast cell columns, in infiltrating mononuclear extravillous trophoblast and in endovascular trophoblast. Villous trophoblast and multinucleate interstitial trophoblast did not label. Extracellular fibronectin was demonstrated amidst sheets of infiltrating extravillous trophoblast. Laminin distribution was similar to that described for fibronectin but laminin was also present in the basement membrane of villous cytotrophoblast. Both fibronectin and laminin showed a pericellular distribution around decidual stromal cells. This study demonstrates further heterogeneity of human trophoblast populations. The presence of fibronectin in infiltrating extravillous trophoblast, endovascular trophoblast and in the distal columns may enhance trophoblast adhesion to maternal tissues and facilitate trophoblast migration.

The human placental bed: histology, immunohistochemistry and pathology

There has been much interest recently on local intra‐uterine materno‐fetal interactions particularly in the placental bed where cellular relationships between mother and fetus are at their most intimate. While few histopathologists are expected to interpret formal placental bed biopsy specimens, confrontation with tissue from this site is common following abortion, post‐partum haemorrhage or molar gestation. This review gives an account of recent advances in our knowledge of the histology, immunohistochemistry and pathology of the placental bed. It focuses particularly on extravillous trophoblast populations and their relationship to maternal cells and emphasizes the importance of vascular changes.

Detection of fetal DNA in trans‐cervical swabs from first trimester pregnancies by gene amplification: a new route to prenatal diagnosis?

Objective To determine whether fetal sex can be predicted from fetal DNA retrieved transcervically from the lower part of the uterine cavity in the first trimester of pregnancy.

Complement component deposition in utero-placental (spiral) arteries in normal human pregnancy

There is conflicting evidence for the deposition of complement in spiral arteries in normal and abnormal human pregnancies. The immunogold silver staining (IGSS) technique was used to investigate the distribution of C1q, C3d, C4, C6 and C9 within the spiral arteries of formalin-fixed normal pregnancy hysterectomy specimens ranging in gestational age from 4 to 40 weeks. Deposition of complement components studied was observed in all cases suggesting classical pathway activation. Reactivity was not confined to vessels showing endovascular trophoblast though the latter showed a characteristic linear deposition subjacent to the trophoblast. Reactivity was most intense for C3d and C9. An appreciation of complement deposition as a feature of normal pregnancy is essential before significant immunopathology can be recognised in placental bed vessels in abnormal pregnancy.

Immunohistological and biochemical evidence for a role for hyaluronic acid in the growth and development of the placenta

A monoclonal antibody, designated NDOG1, has been used to stain a series of human and monkey placentae as well as several adult human tissues using immunoperoxidase techniques. In early placentae, NDOG1 was found to stain extracellular material associated with proliferating, extravillous cytotrophoblast cell columns and with the cytotrophoblast shell at the feto-maternal junction. The immunohistology suggests that NDOG1 antigen may be secreted by the anchoring cytotrophoblast into the immediately adjacent maternal tissues. NDOG1 antibody also shows extracellular staining in the stroma of early human placentae and reacted with the apical villous syncytiotrophoblast plasma membrane throughout pregnancy. Biochemical experiments demonstrated that extracts of this latter membrane contained NDOG1 antigenic activity which was susceptible to digestion with bovine testicular hyaluronidase. Hyaluronic acid was the only glycosaminoglycan found in this membrane, thereby implying a reaction between NDOG1 antibody and hyaluronic acid. Whilst no such direct interaction could be demonstrated in vitro, NDOG1 was shown to compete with two other antibodies which themselves demonstrated specificity for hyaluronic acid. The proposed identity between the NDOG1 antigen and hyaluronic acid is discussed particularly in terms of placentation where the distribution of NDOG1 staining may confirm the role of hyaluronic acid in providing an open matrix structure during stages of cell proliferation, migration and invasion.

Subinvolution of the uteroplacental arteries in the human placental bed

Subinvolution of the uteroplacental arteries of the placental bed is a recognized cause of post partum haemorrhage causing significant morbidity. Whilst the physiological changes in these arteries during pregnancy and the part played by endovascular trophoblast migration are well documented, the sequence of events during involution and the pathophysiology of subinvolution are unknown. Using immunohistochemical techniques we have studied uteroplacental arteries in the placental bed in 25 cases of post partum haemorrhage and compared the subinvoluted vessels with normally involuted vessels. Non‐involuted vessels were present in 22 test cases; these abnormal vessels were filled with thrombus and no endothelial lining was detected. Extravillous perivascular trophoblast was usually present in the walls of these abnormal vessels and in some cases was seen in an endovascular position. Subinvolution of placental site vessels may represent an abnormal interaction between maternal uterine cells and fetal trophoblast.