Intervillous Space Of Placenta Research Articles

Placental Malaria: A New Insight into the Pathophysiology.

Malaria in pregnancy poses a great health risk to mother and her fetus and results into complications, such as abortion, still birth, intra uterine growth retardation, and low birth weight. The heavy infiltration of Plasmodium falciparum-infected RBCs in the intervillous spaces of placenta seems to be responsible for all the complications observed. Infected RBCs in the placenta cause an inflammatory environment with increase in inflammatory cells and cytokines which is deleterious to the placenta. Increased inflammatory responses in the infected placenta result into oxidative stress that in turn causes oxidative stress-induced placental cell death. Moreover, heat shock proteins that are produced in high concentration in stressed cells to combat the stress have been reported in fewer concentrations in malaria-infected placenta. Pathologies associated with placental malaria seems to be the effect of a change in immune status from antibody-mediated immune response to cell-mediated immune response resulting into excess inflammation, oxidative stress, apoptosis, and decreased heat shock protein expression. However, we also need to study other aspects of pathologies so that better drugs can be designed with new molecular targets.

Low Fetal Weight is Directly Caused by Sequestration of Parasites and Indirectly by IL-17 and IL-10 Imbalance in the Placenta of Pregnant Mice with Malaria.

The sequestration of infected erythrocytes in the placenta can activate the syncytiotrophoblast to release cytokines that affect the micro-environment and influence the delivery of nutrients and oxygen to fetus. The high level of IL-10 has been reported in the intervillous space and could prevent the pathological effects. There is still no data of Th17 involvement in the pathogenesis of placental malaria. This study was conducted to reveal the influence of placental IL-17 and IL-10 levels on fetal weights in malaria placenta. Seventeen pregnant BALB/C mice were divided into control (8 pregnant mice) and treatment group (9 pregnant mice infected by Plasmodium berghei). Placental specimens stained with hematoxylin and eosin were examined to determine the level of cytoadherence by counting the infected erythrocytes in the intervillous space of placenta. Levels of IL-17 and IL-10 in the placenta were measured using ELISA. All fetuses were weighed by analytical balance. Statistical analysis using Structural Equation Modeling showed that cytoadherence caused an increased level of placental IL-17 and a decreased level of placental IL-10. Cytoadherence also caused low fetal weight. The increased level of placental IL-17 caused low fetal weight, and interestingly low fetal weight was caused by a decrease of placental IL-10. It can be concluded that low fetal weight in placental malaria is directly caused by sequestration of the parasites and indirectly by the local imbalance of IL-17 and IL-10 levels.

An Upstream Open Reading Frame Controls Translation of var2csa, a Gene Implicated in Placental Malaria

Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue.

Stereological Analysis of Mature Human Placenta of Pregnant Women of Different Age

The normal placentas, regular pregnancies and deliveries were structurally examined. The aim of this research was to compare the results and to confirm if there were some difference in the structure of placenta related to the age of pregnant women. We examined 30 human placentas. The examined group of women were divided into two groups: 1) pregnant women 20-35 years old; 2) pregnant women over 35 years old. The stereological method was used. The volume density, absolute volume, the surface density and absolute surface of terminal villi of placentas in younger and older pregnant women were not significantly different. The volume density, absolute volume, the surface density and absolute surface of the other placentas villi in younger pregnant women compared to older ones, were significantly increased (p<0.001). The volume density of fibrinoid of placentas in older pregnant women compared to younger ones was significantly increased (p<0.02). The surface density, absolute volume and absolute surface of fibrinoid in these two examined groups of pregnant women were not significantly different. The volume density of intervillous space of placentas in older pregnant women compared to younger ones was significantly increased (p<0.05). Absolute volumes of intervillous space of placentas in these two examined groups of pregnant women are not significantly different.

Materno-fetal passage of nutritive and inhalant allergens across placentas of term and pre-term deliveries perfused in vitro.

The pre- and postnatal environment appears to be of crucial importance for the manifestation of allergic diseases, which often begin during infancy. Although T cell reactivity of fetal origin to a range of common allergens is present in most cord blood samples, the immunological basis remains unclear. In order to test the hypothesis of transplacental allergen transfer we studied double-sided open ex vivo perfusion experiments of isolated placental cotyledons with the nutritive allergens beta-lactoglobulin (BLG) and ovalbumin (OVA) and the inhalant major birch pollen allergen Bet v1. Placentas of full-term and pre-term newborns were obtained immediately after delivery to recover functionally active maternal and fetal circulations. Thus, a fetal artery and a fetal vein were cannulated and perfused with pure medium (fetoplacental circulation), whereas the intervillous space of placentas was flushed with allergen containing medium by puncture of the basal plate (maternoplacental circulation). Samples that were collected throughout the perfusion experiment from fetal venous outflow were tested by allergen-specific enzyme-linked immunosorbent assays (ELISA) for the presence of allergens indicative of materno-fetal transplacental passage. We observed transplacental transfer of BLG, OVA and Bet v1 in placentas of term as well as premature deliveries. The respective allergen was readily detectable in fetal effluent at the beginning of the perfusion experiment and allergen levels reached a plateau after about 2 h. The steady state transfer rate of BLG and OVA in term placentas was 0.012% +/- 0.001 and 0.013% +/- 0.001 of total dose, i.e. 130.21 +/- 7.41 ng/mL and 115.83 +/- 6.07 ng/mL, respectively. The observed transfer rate of Bet v1 after 2h of perfusion was 0.155% +/- 0.034 of total dose, that is 2.41 +/- 1.36 ng/mL. Transplacentally transferred concentration of BLG and OVA in pre-term placentas increased continuously throughout perfusion time from 5.32 +/- 0.92 ng/mL at 1 min to 87.53 +/- 21.93 ng/mL at 120 min and 1.35 +/- 0.31 ng/mL at 1 min to 112.87 +/- 5.25 ng/mL at 150 min, respectively. Allergen-specific cord blood reactivity may be attributed to low levels of allergens crossing the human placenta and providing the fetus with the necessary stimulus for T cell priming.

Placental malaria is associated with cell-mediated inflammatory responses with selective absence of natural killer cells.

Immunosuppression, particularly of cell-mediated responses, has classically been thought to play a major role in the increased susceptibility to malaria observed in pregnant women. An immunohistochemical characterization of the inflammatory infiltrate in a group of 41 placentas from women living in a Plasmodium falciparum-hyperendemic area in Tanzania revealed a marked increase in the number of monocytes and macrophages and cytotoxic T cells in the intervillous space of placentas with active malaria infection, compared with noninfected placentas, placentas from women with past infection, and a control group of placentas from Spain. This increase was associated with the severity of the infection. High numbers of monocytes and macrophages were associated with low birth weight. We also detected a complete absence of NK cells in the intervillous space in all placentas. This apparently physiological absence of NK cells may contribute to hindering the clearance of the parasite. These results indicate that placental malaria does not appear to be associated with cell-mediated immunosuppression. The role of the absence of NK cells in increased susceptibility to malaria needs to be further elucidated.

Characterization of Proteoglycans of Human Placenta and Identification of Unique Chondroitin Sulfate Proteoglycans of the Intervillous Spaces That Mediate the Adherence ofPlasmodium falciparum-infected Erythrocytes to the Placenta

In pregnant women infected with Plasmodium falciparum, the infected red blood cells (IRBCs) selectively accumulate in the intervillous spaces of placenta, leading to poor fetal outcome and severe health complications in the mother. Although chondroitin 4-sulfate is known to mediate IRBC adherence to placenta, the natural receptor has not been identified. In the present study, the chondroitin sulfate proteoglycans (CSPGs) of human placenta were purified and structurally characterized, and adherence of IRBCs to these CSPGs investigated. The data indicate that the placenta contains three distinct types of CSPGs: significant quantities of uniquely low sulfated, extracellular CSPGs localized in the intervillous spaces, minor amounts of two cell-associated CSPGs, and major amounts of dermatan sulfate-like CSPGs of the fibrous tissue. Of the various CSPGs isolated from the placenta, the low sulfated CSPGs of the intervillous spaces most efficiently bind IRBCs. Based on IRBC adherence capacities and localization patterns of various CSPGs, we conclude that the CSPGs of the intervillous spaces are the receptors for placental IRBC adherence. The identification and characterization of these CSPGs provide a valuable tool for understanding the precise molecular interactions involved in placental IRBC adherence and for the development of therapeutic strategies for maternal malaria. In the accompanying paper (Alkhalil, A., Achur, R. N., Valiyaveettil, M., Ockenhouse, C. F., and Gowda, D. C. (2000) J. Biol. Chem. 275, 40357-40364), we report the structural requirements for the IRBC adherence.

Hydrogen concentration, carbon dioxide tension and acid base balance in blood of human umbilical cord and intervillous space of placenta.

Hydrogen concentration, carbon dioxide tension and acid base balance in blood of human umbilical cord and intervillous space of placenta.