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Angiogenesis and vascular remodeling are crucial processes in tumor invasion and metastasis as well as in embryo implantation and normal development of the placenta. We have previously shown that hCG expressed in trophoblast and various malignant tumors promotes cellular motility and that uterine endothelium expresses hCG/LH receptor in vivo. In this study hCG was proposed to promote angiogenesis. A three-dimensional in vitro angiogenesis system consisting of uterine microvascular endothelial cells seeded on microcarriers and entrapped in a fibrin matrix was used to study the influence of hCG on neovascularization. Physiological concentrations of hCG (5-50,000 mU/ml) significantly increased in vitro capillary formation (up to 2.5-fold) and migration of endothelial cells in a Boyden chamber assay (up to 3.6-fold) in a dose-dependent manner, whereas hCG had no effect on cell proliferation. In vivo, hCG induced neovascularization in the chicken chorioallantoic membrane assay comparable to the activity of vascular endothelial growth factor. hCG-secreting tumors (choriocarcinoma, endometrium, and ovarian carcinoma) promoted in vitro neovascularization (up to 3-fold), whereas hCG-neutralizing antibody, pertussis toxin (G protein inhibitor), or GRGDTP peptide (integrin antagonist), respectively, abolished both tumor- and hCG-induced capillary sprout formation. Our data indicate a novel function for hCG in uterine adaptation to early pregnancy as well as in tumor development and underline the importance of hCG as an as yet unrecognized angiogenic factor.

Abstract-Although maternal-fetal cholesterol transfer may serve to compensate for insufficient fetal cholesterol biosynthesis under pathological conditions, it may have detrimental consequences under conditions of maternal hypercholesterolemia leading to preatherosclerotic lesion development in fetal aortas. Maternal cholesterol may enter fetal circulation by traversing syncytiotrophoblast and endothelial layers of the placenta. We hypothesized that endothelial cells (ECs) of the fetoplacental vasculature display a high and tightly regulated capacity for cholesterol release. Using ECs isolated from human term placenta (HPECs), we investigated cholesterol release capacity and examined transporters involved in cholesterol efflux pathways controlled by liver-X-receptors (LXRs). HPECs demonstrated 2.5-fold higher cholesterol release to lipid-free apolipoprotein (apo)A-I than human umbilical vein ECs (HUVECs), whereas both cell types showed similar cholesterol efflux to high-density lipoproteins (HDLs). Interestingly, treatment of HPECs with LXR activators increased cholesterol efflux to both types of acceptors, whereas no such response could be observed for HUVECs. In line with enhanced cholesterol efflux, LXR activation in HPECs increased expression of ATP-binding cassette transporters ABCA1 and ABCG1, while not altering expression of ABCG4 and scavenger receptor class B type I (SR-BI). Inhibition of ABCA1 or silencing of ABCG1 decreased cholesterol efflux to apoA-I (Ϫ70%) and HDL 3 (Ϫ57%), respectively. Immunohistochemistry localized both transporters predominantly to the apical membranes of placental ECs in situ. Thus, ECs of human term placenta exhibit unique, efficient and LXR-regulated cholesterol efflux mechanisms. We propose a sequential pathway mediated by ABCA1 and ABCG1, respectively, by which HPECs participate in forming mature HDL in the fetal blood. (Circ Res. 2009;104:600-608.)Key Words: maternal-fetal cholesterol transfer Ⅲ endothelial cells Ⅲ HDL Ⅲ liver X receptors C holesterol is indispensable during fetal development. 1 It has been long assumed that most, if not all, cholesterol required for fetal growth is synthesized de novo by the fetus itself, thus making it autonomous from maternal or placental cholesterol supply. However, several lines of evidence have cast doubt on this notion. 2,3 Fetuses that lack the ability to synthesize cholesterol, such as those with the Smith-LemliOpitz syndrome, are, nevertheless, born with low levels of tissue and plasma cholesterol, indicating that they have acquired maternal cholesterol in utero. 4 Recent exciting studies demonstrated a strong correlation between the size and number of atherosclerotic lesions in human fetal arteries with maternal cholesterol levels. 5,6 Moreover, maternal hypercholesterolemia also modified early predictors of cardiovascular disease in the offspring, thus corroborating the concept of developmental programming of adult disease in human. 7 Considering that progression of atherosclerosis in adults takes ages, these striking resu...

Health problems can develop during a pregnancy, turning it into a high risk. The aim of this study was to explore the influence of hypertensive disorders, gestational diabetes, and preterm birth as risk factors for health-related quality of life (HRQL) and depressive symptoms during late pregnancy and postpartum. A prospective, longitudinal study was performed with three assessments. Ninety women were recruited in the study including 29 controls. HRQL was measured using the WHO-QOL-BREF questionnaire. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS). Statistical analyses were performed using ANOVA and the chi-square test to explore HRQL and depressive symptoms between three pregnancy risk groups and controls. Women of the preterm group had statistically significant higher depression scores and lower HRQL scores on the physical domain during pregnancy than those without complications. Women with hypertensive disorders showed the second most depressive symptoms. Physical and global HRQL improved and depressive symptoms decreased significantly from late pregnancy and early postpartum period to late postpartum. Pregnant specific health problems, especially the risk for preterm delivery is associated with more depressive symptoms and decreased HRQL in pregnancy. Guidance and communication for these women is important. The counseling should be multi professional to reduce childbirth burdens.

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Pregnancy is associated with substantial changes in the haemostatic system and a six-fold higher incidence of venous thromboembolism. Conventional global tests, such as prothrombin time and activated partial thromboplastin time, do not definitely detect this hypercoagulable condition. We investigated whether the changes in haemostatic system during pregnancy are reflected in the calibrated automated thrombography (CAT). Thrombin generation was measured in platelet-poor plasma (PPP) of 150 healthy pregnant women without any pregnancy associated diseases by means of CAT. In addition, prothrombin (FII), antithrombin (AT), protein S, protein C, tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and prothrombin fragments 1+2 (F1+2) were measured. Endogenous thrombin potential (ETP) and peak of thrombin generation increased significantly with gestational weeks, while lag time and time to peak remained unchanged. A significant increase of PAI-1, TFPI, F1+2 and TAT as well as a significant decrease of free protein S, protein S antigen, and protein S activity was observed. Levels of AT and protein C remained stable during pregnancy. Division of population in trimester of pregnancy and analysis of differences between the trimesters showed rather similar results. Our study shows that endogenous thrombin potential does increase with duration of normal uncomplicated pregnancy. Whether parameters of continuous thrombin generation will correlate with thrombembolic disease remains to be shown.

EL is the predominant TLG family member in the human placenta present at both interfaces. EL and LPL are dysregulated in IUGR.