A Case of Intrauterine Growth Restriction in Association with Placental Mesenchymal Dysplasia with Abnormal Placental Lymphatic Development
Maternal and Fetal Health Research Group, University of Manchester, St Mary's Hospital, Manchester M13 0JH, UK.Placenta (Impact Factor: 2.71). 06/2009; 30(7):654-7. DOI: 10.1016/j.placenta.2009.04.004
Placental mesenchymal dysplasia (PMD) is a rare human disorder associated with stillbirth, intrauterine growth restriction (IUGR) and Beckwith-Wiedemann syndrome. Although the morphology of this condition has been described in 86 cases, the underlying cellular origin is unclear. We investigate the placental cell type involved in a case of PMD associated with a live born female infant with IUGR. In PMD intermediate villi contain cisternae, lined by non-proliferative cells. Immunostaining reveals they are not of trophoblast or vascular endothelial origin. There is positive immunostaining for lymphatic endothelium; this abnormal lymphangiogenesis is in concordance with current hypotheses regarding the aetiology of PMD. Furthermore, such observations suggest that placental villous mesenchyme may differentiate into various cell types, even those not normally found in the human placenta.
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ABSTRACT: Scant data on placental lymphatic vessels have pointed to the absence of lymphatic circulation. A recent study on mesenchymal dysplasia (MD), however, has identified pathologic lymphangiogenesis using the D2-40 lymphatic marker. These conflicting data have prompted us to investigate whether lymphatic vessels are present in normal developing placentas and in placental disorders characterized by cistern formation. Seventeen human placentas without significant pathological abnormality ranging from 12 to 39 weeks of gestational age were studied. Cisternal placental disorders were represented by mesenchymal dysplasia (n = 1), partial hydatitiform mole (n = 2), spontaneous abortion (n = 3) and complete hydatiform mole (n = 2). To identify lymphatic vessels, we used lymphatic endothelial markers Prox-1 and D2-40. The pan-endothelial marker CD31 was used to highlight overall placental vasculature and to determine if the lining cells of cisterns were of endothelial origin. Lymphatic marker positivity was assessed in maternal (decidual) as well as in fetal (chorionic villous) vasculature. No staining with Prox-1 or D2-40 was identified in fetal vessels in developing or term placentas, or in selected cisternal placental disorders, although both markers highlighted a number of thin-walled decidual vessels. Cistern lining cells were negative for Prox-1, D2-40 and CD31. D2-40 consistently marked stromal cells in chorionic villi and highlighted perivascular/pericellular extracellular matrix. We established that no lymphatic vasculature is present in the chorionic villi during development, at term or in selected edematous placental disorders. The cisternal lining cells are not endothelial cells; most likely they are of stromal cell origin. Lymphangiogenesis is a part of decidual vascular remodeling during gestation.Placenta 02/2011; 32(4):310-6. DOI:10.1016/j.placenta.2011.01.013 · 2.71 Impact Factor
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ABSTRACT: The aim of this study was to assess the association between genetic variants of the insulin receptor substrate (IRS)-1 gene, platelet function, and long-term outcomes in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease while on aspirin and clopidogrel therapy. The effects of pharmacogenetic determinants on platelet function and cardiovascular outcomes in type DM patients are unknown. The association between IRS-1 genetic variants, platelet function, and the risk of major adverse cardiac events (MACE) at 2 years was assessed in 187 patients with type 2 DM and stable coronary artery disease on maintenance aspirin and clopidogrel therapy. Seven tag single nucleotide polymorphisms were selected. Individuals with high platelet reactivity were more frequent among carriers of the C allele (GC and CC genotypes; approximately 20% of population) of the rs956115 marker (44.4% vs. 20.5%; odds ratio: 3.1, 95% confidence interval [CI]: 1.44 to 6.67; p = 0.006). These patients were at higher risk of MACE (28.0% vs. 10.9%; hazard ratio: 2.90, 95% CI: 1.38 to 6.11; p = 0.005). The C allele carriers of the rs956115 marker were more commonly associated with a hyperreactive platelet phenotype. This was confirmed in an external validation cohort of patients with type 2 DM but not in an external validation cohort of patients without DM. Carriers of the C allele of the rs956115 marker also had a significantly higher risk of MACE compared with noncarriers (30.6% vs. 11.4%; hazard ratio: 2.88, 95% CI: 1.35 to 6.14; p = 0.006). Type 2 DM patients who are carriers of the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and increased risk of MACE.Journal of the American College of Cardiology 06/2011; 58(1):30-9. DOI:10.1016/j.jacc.2011.02.040 · 16.50 Impact Factor
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ABSTRACT: Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while it inhibits it in non-tumor cells. Melatonin kills tumor cells through induction of reactive oxygen species generation and activation of pro-apoptotic pathways. In contrast, melatonin promotes the survival of non-tumor cells due to its antioxidant properties and the inhibition of pro-apoptotic pathways. In primary human villous trophoblast, a known pseudo-tumorigenic tissue, melatonin promotes the survival through inhibition of the Bax/Bcl-2 pathway while in BeWo choriocarcinoma cell line melatonin induces permeabilization of the mitochondrial membrane leading to cellular death. These findings suggest that the trophoblast is a good model to study the differential effects of melatonin on the intrinsic apoptosis pathway. This review describes the differential effects of melatonin on the intrinsic apoptosis pathway in tumor and non-tumor cells and presents the trophoblast as a novel model system in which to study these effects of melatonin.Molecular and Cellular Endocrinology 08/2011; 348(1):1-11. DOI:10.1016/j.mce.2011.08.025 · 4.41 Impact Factor
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