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Vassilis Tsatsaris

Publications and source records attributed to Vassilis Tsatsaris.

12 recordsLinked to original sources
PubMed2005

Stimulation of human trophoblast invasion by placental growth hormone.

A critical step in establishment of human pregnancy is the invasion of the uterus wall by the extravillous cytotrophoblast (EVCT), a process regulated by multiple autocrine and paracrine factors. Hormones belonging to the GH/prolactin family are expressed at the maternofetal interface. Because they are involved in cell motility in various models, we examined the possible regulatory role of human placental GH (hPGH) in EVCT invasiveness. By using an in vitro invasion model, we found that EVCT isolated from first-trimester chorionic villi and cultured on Matrigel secreted hPGH and expressed human GH receptor (hGHR). These data were confirmed by in situ immunohistochemistry. EVCT expressed the full-length and truncated forms of hGHR, and the Janus kinase-2/signal transducer and activator of transcription factor-5 signaling pathway was activated in EVCT by hPGH treatment. Strong hPGH and hGHR expression was observed when EVCT invaded Matrigel and moved through the pores of the filter on which they were cultured. hPGH stimulated EVCT invasiveness, and this effect was inhibited by a Janus kinase-2 inhibitor. Interestingly, hPGH was more efficient than pituitary GH in stimulating EVCT invasiveness. These results offer the first evidence for a placental role of hPGH and suggest an autocrine/paracrine role of hPGH in the regulation of trophoblast invasion.

Cells, Cultured↗
PubMed2005

Shunting the intervillous space: new concepts in human uteroplacental vascularization.

OBJECTIVE: It is supposed that the intervillous space is not perfused by maternal blood during the first trimester, suggesting vascular shunts in the myometrium. We therefore attempted to provide arguments for a functional vascular anastomotic network located in the placental bed during human pregnancy. STUDY DESIGN: Three-dimensional (3D) sonography, laboratory analyses, and anatomic studies (hysterectomy specimens, uteroplacental vascular cast) were performed. RESULTS: Color Doppler showed a vascular network with anastomotic aspect located in the placental bed. A vascular cast of a uterus, obtained after postpartum hemorrhage, demonstrated a vascular anastomotic network in the myometrium. Higher PO2 levels in the uterine vein compared with the intervillous space confirmed the functional nature of this shunt. Low resistances in the uterine arteries during the first week after delivery suggested that this vascular network remains functional after placental expulsion. CONCLUSION: Our studies have yielded functional and anatomic evidence of an arteriovenous shunt located in the subplacental myometrium.

Cross-Sectional Studies↗
PubMed2004

Lipids from oxidized low-density lipoprotein modulate human trophoblast invasion: involvement of nuclear liver X receptors.

Human embryonic implantation involves major invasion of the uterine wall and remodeling of the uterine arteries by extravillous cytotrophoblast cells (EVCT). Abnormalities in these early steps of placental development lead to poor placentation and fetal growth defects and are frequently associated with preeclampsia, a major complication of human pregnancy. We recently showed that oxidized low-density lipoproteins (oxLDLs) are present in situ in EVCT and inhibit cell invasion in a concentration-dependent manner. The aim of the present study was to better understand the mechanisms by which oxLDL modulate trophoblast invasion. We therefore investigated the presence of oxLDL receptors in our cell culture model of human invasive primary EVCT. We found using immunocytochemistry and immunoblotting that the lectin-like oxLDL receptor-1 was the scavenger receptor mainly expressed in EVCT and was probably involved in oxLDL uptake. We next examined the effect of low-density lipoprotein oxidative state on trophoblast invasion in vitro using EVCT cultured on Matrigel-coated Transwell. We demonstrated that only oxLDL containing a high proportion of oxysterols and phosphatidylcholine hydroperoxide derivatives that provide ligands for liver X receptor (LXR) and peroxisomal proliferator-activated receptor gamma (PPARgamma), respectively, reduced trophoblast invasion. We next investigated the presence and the role of these nuclear receptors and found that in addition to PPARgamma, human invasive trophoblasts express LXRbeta, and activation of these nuclear receptors by specific synthetic or natural ligands inhibited trophoblast invasion. Finally, using a PPARgamma antagonist, we suggest that LXRbeta, rather than PPARgamma, is involved in oxLDL-mediated inhibition of human trophoblast invasion in vitro.

Cell Nucleus↗
PubMed2004

Monoamniotic twin pregnancies: antenatal management and perinatal results of 19 consecutive cases.

OBJECTIVE: To describe the obstetric management and perinatal outcome of antenatally diagnosed monoamniotic twin pregnancies (MATP) in a tertiary level maternity unit. SETTING: Port-Royal Maternity Hospital, Paris, France. POPULATION: MATP that progressed beyond 22 weeks seen from 1993 to 2001. METHODS: A retrospective chart review of all twin pregnancies. Diagnosis of MATP was made by ultrasonography and confirmed by placental pathology. MAIN OUTCOME MEASURE: Perinatal mortality. RESULTS: Among the 1242 twins pregnancies delivered during the study period, 19 were monoamniotic. Four fetuses (10% of all births) had malformations. Perinatal mortality was high (n= 12, 32%) because of fetal deaths (nine cases) and very preterm births (three neonatal deaths). No fetal deaths occurred after 29 weeks. Of the 15 women with at least one live fetus before labour, 6 gave birth by vaginal delivery (40%). No obstetric accidents occurred during vaginal deliveries. CONCLUSION: Perinatal mortality of MATP is still very high, even with accurate, early antenatal diagnosis, intensified surveillance and delivery provided in a tertiary level hospital. The main causes of perinatal deaths are cord accidents in utero, congenital anomalies and very preterm births.

Adult↗
PubMed2004

Oxidized low-density lipoproteins inhibit trophoblastic cell invasion.

Human implantation involves a major invasion of the uterine wall and remodeling of the uterine arteries by trophoblastic cells. Abnormalities in these early steps of placental development lead to poor placentation, fetal growth defects and are frequently associated with pre-eclampsia, a serious disease specific to human pregnancy. Lipid metabolism is altered during human pregnancy, with low-density lipoproteins (LDL) becoming more susceptible to oxidation. The aim of this study was to localize oxidized LDL (oxLDL) at the implantation site and to investigate the role of oxLDL in human trophoblast invasion in vitro. We showed by immunohistochemistry that oxLDL was present in cytotrophoblasts of villous and extravillous origin in sections of first trimester human placenta. We purified primary invasive extravillous cytotrophoblasts isolated from the chorionic villi of human first trimester placenta and cultured them on Matrigel-coated transwells. We demonstrated using this invasion assay that oxLDL, but not native LDL, inhibited cell invasion in a concentration-dependent manner. These results suggest that human trophoblast invasion may be modulated by oxLDL in vivo and provide new insights into the pathophysiology of pre-eclampsia associated with oxidative stress and defective trophoblast invasion.

Cells, Cultured↗
PubMed2004

Pharmacokinetics of tocolytic agents.

Tocolytic agents are drugs designed to inhibit contractions of myometrial smooth muscle cells. Such an effect has been demonstrated in vitro or in vivo for several pharmacological agents, including beta-adrenergic agonists, calcium channel antagonists, oxytocin antagonists, NSAIDs and magnesium sulfate. However, the aim of tocolysis is not only to stop uterine contractions or to prevent preterm delivery, but to prevent perinatal morbidity and mortality associated with preterm birth. The achievement of this goal has not yet been clearly demonstrated for any of the drugs available, and the use of tocolytic agents may appear controversial. Therefore, it is important to avoid maternal and fetal toxicity when tocolytic agents are used. During pregnancy, all steps of drug pharmacokinetics are altered. Absorption of drugs administered orally is limited because of delayed stomach emptying and reduced intestinal motility. The volume of distribution of drugs is increased. The metabolic activity of the liver is increased, accelerating the metabolism of lipophilic drugs. Renal filtration is increased, leading to enhanced renal elimination of water-soluble drugs. These modifications are generally responsible for reduced plasma concentration and reduced half-life of most drugs. These specific modifications have to be taken into account when using a drug in pregnant women. The aim of this review is to provide the reader with pharmacological data about drugs currently used to treat preterm labour. Such data in pregnant women may affect the choice of optimal drug dosage and route of administration.

Adrenergic beta-Agonists↗
PubMed2004

Atosiban for preterm labour.

Oxytocin antagonists are synthetic analogues that have the nonapeptide structure of oxytocin. They act by competing with oxytocin for receptors in the myometrium. Animal experiments and pilot clinical studies have examined several agents and, of these, atosiban has been the object of extensive clinical trials. In a large placebo-controlled trial with >500 patients, atosiban reduced the number of premature deliveries over 7 days compared with placebo with no more adverse effects than placebo. In large multicentre studies comparing atosiban with beta-adrenoceptor agonists, the efficacy of the two medications was similar for pregnancy prolongation for 48 hours and for 7 days. The adverse effects, particularly cardiovascular, were considerably more frequent in the patients receiving beta-adrenoceptor agonists, who had to stop treatment significantly more often than the atosiban recipients. No fetal adverse effects were seen with atosiban and, in particular, no effect on baseline fetal heart rate, unlike with the beta-adrenoceptor agonists. Neonatal outcome did not differ significantly according to the treatment. The usefulness of maintenance treatment after the initial 48 hours has not been confirmed. Thus, the effectiveness of oxytocin antagonists appears to be similar to beta-adrenoceptor agonists and the former are not accompanied by measurable adverse effects. Oxytocin antagonists were designed specifically as tocolytics and have been validated by the European Drug Agency. They may be the treatment of choice for preterm labour, particularly in patients at risk of cardiovascular complications (e.g. multiple pregnancy, heart disease, etc.).

Adrenergic beta-Agonists↗
PubMed2003

Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences.

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development.

Adult↗
PubMed2002

Calcitonin gene-related peptide (CGRP) and CGRP receptor expression at the human implantation site.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide produced by tissue-specific alternative splicing of the primary transcript of the calcitonin gene. The objectives of this study were: 1) to determine the expression of CGRP and its receptor at the human implantation site, and 2) to examine the possible in vitro effect of this neuropeptide on two major partners of implantation, decidual cells and extravillous cytotrophoblasts. Immunohistological analysis of first-trimester placental chorionic villi showed CGRP in decidual cells and glandular cells, but not in extravillous trophoblast cells. CGRP expression was confirmed in cultured decidual cells by Southern blot analysis and immunocytochemistry and by RIA in culture medium. Transcripts of calcitonin receptor-like receptor were detected by Southern blot analysis of RT-PCR amplicons from both decidual and extravillous trophoblast cells, whereas transcripts for the receptor activity-modifying protein 1 were detected in decidual cells only. In vitro, CGRP stimulated cAMP production but not nitric oxide (NO) release by cultured decidual cells; in contrast CGRP increased NO release but not cAMP production in cultured extravillous trophoblasts. The presence of NO synthase (endothelial and inducible) was confirmed by immunodetection in extravillous trophoblasts, both in situ and in vitro. This study points to a paracrine and autocrine effect of CGRP on decidual and extravillous trophoblast cells, two major actors in implantation.

Alternative Splicing↗