title: Imbalance of mononuclear cell infiltrates in the placental tissue from foetuses after spontaneous abortion versus therapeutic termination from 8th to 12th weeks of gestational age.
abstract: Placental macrophages (Hofbauer cells) are located close to trophoblastic cells and foetal capillaries, which make them perfect candidates for involvement in regulatory processes within the villous core. Their capacity of producing several cytokines and prostaglandin-synthesising enzymes, and expressing vascular endothelial growth factor, indicate a possible role in placental development and angiogenesis in order to support pregnancy. Common cells to Hofbauer macrophages sharing similar cell surface markers (HLA-A, -B, -C and leukocyte common antigen) have been reported in the stroma, decidua and amnion, indicating additional foetal protection. Yet this is not always the case. Most spontaneous abortions occur before 12 weeks' gestation, and most are due to chromosomal errors in the conceptus. Relatively few truly spontaneous abortions take place between 12 and 20 weeks' gestation. Thereafter, between 20 and 30 weeks, another type of premature spontaneous termination becomes prevalent, which is due to ascending infection. The numbers of cells expressing the various markers of the monocytemacrophage lineage change throughout pregnancy. In the present study, we investigated the immunohistochemical expression of mononuclear infiltrations in paraffin-embedded placentas, from foetuses after spontaneous abortion (8th, 10th and 12th weeks of gestational age), and those after therapeutic abortion at the same time, using a panel of monoclonal antibodies for the identification of leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26), T lymphocytes (CD45RO/UCHL1), CD68 and CD14 cells. Immunologic factors in human reproductive failure are plausible mechanisms of infertility and spontaneous abortion. Approximately 25% of cases of premature ovarian failure appear to result from an autoimmune aetiology. Unfortunately, current therapeutic options for these women are limited to exogenous hormone or gamete substitution. Local inflammations at the sites of endometriosis implants are postulated to mediate the pain and reduced fecundability associated with this clinical syndrome. The recruitment of immune cells, particularly monocytes and T-cells, neovascularisation around foci of invading peritoneal lesions, and the possible development of antiendometrial autoantibodies support an immunologic basis of this disorder. To date, treatment of pain and infertility associated with endometriosis is primarily surgical, although immune-based adjuvants are theoretical possibilities for the future. Finally, although hypotheses supporting immunologic mechanisms of recurrent pregnancy loss have been popular over the past decade, most clinical investigations in this area do not provide compelling evidence for this position. Reputable specialists in reproductive medicine use experimental immunotherapies judiciously in selected cases of repetitive abortion. For example, the use of anticoagulation therapy can be beneficial in cases with documented antiphospholipid antibodies. At present, however, efficacious immunotherapy protocols for general application have not been established. Despite these caveats, continued strides in our understanding of human reproductive immunology should yield considerable future progress in this field. During the physiological changes that occur in the first and in the beginning of the second trimester of pregnancy, spiral arteries of the placental bed are converted into the uteroplacental arteries. The essence of this conversion consists of losing the muscular elements in the vessel walls, making them unable to respond to vasomotor influences. Cells that infiltrate the walls of spiral arteries and replace their normal elements are called migratory, non-villous or intermediate trophoblastic cells. Besides infiltrating and replacing the anatomic structures of spiral arteries, intermediate trophoblastic cells also penetrate into the lumina of these vessels forming endovascular plugs. These plugs are one of the reasons why early uteroplacental blood flow cannot be visualised, even with transvaginal ultrasound, during the first 12 weeks of gestation. In uncomplicated pregnancies, the endovascular trophoblast is bound to disappear by the end of the second trimester of pregnancy, but the literature on this topic is scarce. Here we describe the detection, isolation and characterisation of CD45RO-, L26- and CD68/CD14-positive cells from human early pregnancy deciduas. These cells were found in close vicinity to endometrial glands, with preference to the basal layer of the decidua. We conclude that (1) maternal cells, apparently CD45RO/UCHL1-positive cells, cross the maternofoetal barrier and participate in spontaneous (involuntary) abortions, and (2) a small proportion of maternal cells (approximately 30%), apparently CD68/CD14-positive cells, also cross the maternal-foetal barrier and cause growth delay and recurrent reproductive failure. Further investigation of involvement of the intercellular adhesion molecules 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin in leukocyte accumulation will be needed to support the passage of maternal cells to the foetus. The results were statistically significant (P<0.0001, Student's t-test).
authors.affiliation: Department of Histology-Embryology, Democritus University of Thrace, Dragana, 68100, Alexandroupolis, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Lambropoulou
authors.forename: D
authors.initials: D
authors.lastname: Tamiolakis
authors.forename: J
authors.initials: J
authors.lastname: Venizelos
authors.forename: V
authors.initials: V
authors.lastname: Liberis
authors.forename: G
authors.initials: G
authors.lastname: Galazios
authors.forename: P
authors.initials: P
authors.lastname: Tsikouras
authors.forename: D
authors.initials: D
authors.lastname: Karamanidis
authors.forename: G
authors.initials: G
authors.lastname: Petrakis
authors.forename: T
authors.initials: T
authors.lastname: Constantinidis
authors.forename: M
authors.initials: M
authors.lastname: Menegaki
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
mesh_terms: D000028:Abortion, Induced; D000022:Abortion, Spontaneous / Q000276:immunology* / Q000473:pathology; D000032:Abortion, Therapeutic; D000367:Age Factors; D015703:Antigens, CD / Q000032:analysis; D003656:Decidua / Q000276:immunology / Q000473:pathology; D004717:Endometrium / Q000276:immunology / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010920:Placenta / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D015703:Antigens, CD