Feto-placental Interface Research Articles

High maternal BMI and low maternal blood BDNF may determine the limit of detection of amniotic fluid BDNF throughout gestation: Analysis of mother-fetus trios and literature review

ObjectiveAn increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF).MethodsIn this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay.ResultsIn 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01).ConclusionOur study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.

Mouse Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Perinatal Brain Injury Via a CD8+ T Cell Mechanism in a Model of Intrauterine Inflammation.

The objective of this study was to determine if mouse bone marrow-derived mesenchymal stem cells (BMMSCs) ameliorate preterm birth and perinatal brain injury induced by intrauterine inflammation (IUI). A mouse model of IUI-induced perinatal brain injury at embryonic (E) day 17 was utilized. BMMSCs were derived from GFP-transgenic mice and phenotypically confirmed to be CD44+, Sca-1+, CD45-, CD34-, CD11b-, and CD11c- by flow cytometry and sorted by fluorescence-activated cell sorting (FACS). Dams were assigned to four groups: phosphate-buffered saline (PBS) + PBS, PBS + BMMSCs, lipopolysaccharide (LPS) + PBS, and LPS + BMMSCs. Following maternal IUI, there was a significant increase in CD8+ T cells in the placentas. Maternally administered BMMSCs trafficked to the fetal side of the placenta and resulted in significantly decreased placental CD8+ T cells. Furthermore, fetal trafficking of maternally administered BMMSCs correlated with an improved performance on offspring neurobehavioral testing in LPS + BMMSC group compared with LPS + PBS group. Our data support that maternal administration of BMMSCs can alleviate perinatal inflammation-induced brain injury and improve neurobehavioral outcomes in the offspring via CD8+ T cell immunomodulation at the feto-placental interface.

Neonatal HDL Counteracts Placental Vascular Inflammation via S1P-S1PR1 Axis.

Placental inflammation and dysfunction during pregnancy are associated with short- and long-term adverse outcomes for the offspring. However, the mechanisms of vascular protection at the feto-placental interface are still poorly investigated. The high-density lipoprotein (HDL) associated sphingosine-1-phosphate (S1P) has been described as a powerful anti-inflammatory complex. This study aimed to elucidate the role of cord blood-derived HDL (nHDL) in feto-placental endothelial dysfunction. Here, we report that the exposure of primary fetal placental arterial endothelial cell (fPAEC) to healthy nHDL-S1P attenuated the ability of TNFα to activate NF-κB signaling and increase the expression of pro-inflammatory markers. Moreover, the angiotensin II (AngII)-induced reactive oxygen species (ROS) production was blunted in the presence of nHDL, whereas it was preserved when the cells were preincubated with S1P receptor antagonists, suggesting that S1P accounts for the vascular protective function of nHDL at the feto-placental unit. These results highlight the importance of HDL and S1P metabolism and signaling in pregnancy pathophysiology.

The Human Placenta in Diabetes and Obesity: Friend or Foe? The 2017 Norbert Freinkel Award Lecture.

The placenta plays a key role in sustaining fetal growth and development. Due to its position between mother and fetus, it is exposed to changes in the intrauterine environment in both circulations. The relative influence of changes in those circulations depends on the period of gestation. Early in pregnancy, maternal influences prevail and may affect the complex biological processes characteristic for this pregnancy period, such as placentation, early cell differentiation, and spiral artery remodeling. It is still unclear whether the placenta early in pregnancy is a friend or foe for the fetus. Later in pregnancy, when the fetal circulation is gradually establishing, fetal signals gain importance in regulating placental structure and function. Many of the placental alterations seen at term of pregnancy are the result of fetoplacental interactions often driven by fetal signals associated with maternal diabetes or obesity. These alterations, such as hypervascularization or enhanced cholesterol removal from placental endothelial cells, can be regarded as adaptations to maintain homeostasis at the fetoplacental interface and, thus, to protect the fetus. However, extreme conditions such as poorly controlled diabetes or pronounced obesity may exceed placental homeostatic capacity, with potentially adverse consequences for the fetus. Thus, in late pregnancy, the placenta acts mostly as a friend as long as the environmental perturbations do not exceed placental capacity for mounting adaptive responses.

Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women

Objective: Fetal fatty acid (FA) delivery is ultimately controlled by placental transport. Focus has been the maternal-placental interface, but regulation at the feto-placental interface is unknown.Methods: Placental macrovascular endothelial cells (EC) (n = 4/group) and trophoblasts (TB) (n = 5/group) were isolated from lean (pregravid BMI <25 kg/m2) and obese (body mass index (BMI) > 30) women. Fatty acid transporters FAT/CD36, FABPpm, FATP4, FABP 3, 4 and 5, PLIN2 and PPARα, δ, γ expression, was measured in EC and TB. Transporter response to 24 h palmitate (PA) was assessed.Results: mRNA expression of FABP3, 4, 5 and PPARγ was 2- to 3-fold reduced in EC of obese versus lean women (p < .03), but not in TB. Protein level of FABPpm was 20% lower in obese (p < .05). Palmitate (PA) up-regulated CD36, FABP3, FABP4, and PLIN2 gene expression by 3- to 4-fold in lean but not obese EC (p < .05), while PA increased FABP4 and PLIN2 in lean and obese TB, and FABP5 in lean (p < .05) EC. PA exposure up-regulated peroxisome proliferator activated receptors (PPARs) 2-fold in lean and obese EC (p < .05), but not in TB.Conclusions: In obese women, FA transporter expression is lower in placental EC, but not TB, and less sensitive to saturated FA, compared to lean women. FA transport may be regulated at the feto-placental interface.

OP 51 Fetal cholesterol deprivation in IUGR is caused by lower fetal synthesis rates

Introduction Fetal cholesterol levels are low in IUGR. Objectives We aimed at analyzing fetal cholesterol precursors, oxidation products, and plant sterols to gain deeper insights into fetal cholesterol metabolism in IUGR. Material and methods Umbilical cord sera were sampled from fetuses delivered between 24 weeks of gestation till term. 49 IUGR fetuses were matched to 49 adequate for age delivered preterm and term neonates (CTRL) according to gestational age at delivery. Sterols were analyzed by GC?MS. Concentration levels were accomplished by apolipoprotein profiling and discussed at the background of a lower cholesterol acceptor capacity in IUGR. Results In the IUGR group, total cholesterol concentrations were about 20% lower when compared to CTRL (p 0.50), while in the CTRL group phytosterol levels were correlated to HDL-cholesterol (rho > 0.50) and ApoA1 (rho > 0.40) underlining the important role of HDL, apoA1 and apoE as a cholesterol acceptors at the fetoplacental interface. 24- and 27-hydroxysterol to cholesterol ratios were higher in IUGR as compared to CTRL (p Conclusions The data suggest that fetal cholesterol synthesis rates is balanced in the HMG-CoA reductase pathway and in the Kandutsch-Russel pathway. The Bloch-pathway is activated in IUGR possibly to counterbalance higher cholesterol turnover rates. However, one cannot exclude additional desmosterol (or precursors) supply by the mother. Of interest, plant sterols in IUGR are highly correlated to apoE underlining the role of apoE as an important cholesterol acceptor at the feto-placental interface. Understanding the fetal cholesterol metabolism is important at the background of new therapy strategies, for example statin treatment in preeclampsia.

Apelin Controls Fetal and Neonatal Glucose Homeostasis and Is Altered by Maternal Undernutrition.

The adequate control of glucose homeostasis during both gestation and early postnatal life is crucial for the development of the fetoplacental unit and adaptive physiological responses at birth. Growing evidences indicate that apelin and its receptor, APJ, which are expressed across a wide range of tissues, exert important roles in glucose homeostasis in adults. However, little is known about the function of the apelinergic system during gestation. In this study, we evaluated the activity of this system in rats, the role of apelin in fetal and neonatal glucose homeostasis, and its modulation by maternal food restriction. We found that 1) the apelinergic system was expressed at the fetoplacental interface and in numerous fetal tissues, 2) ex vivo, the placenta released high amounts of apelin in late gestation, 3) intravenous apelin injection in mothers increased the transplacental transport of glucose, and 4) intraperitoneal apelin administration in neonates increased glucose uptake in lung and muscle. Maternal food restriction drastically reduced apelinemia in both mothers and growth-restricted fetuses and altered the expression of the apelinergic system at the fetoplacental interface. Together, our data demonstrate that apelin controls fetal and neonatal glucose homeostasis and is altered by fetal growth restriction induced by maternal undernutrition.

PO-0364 Histological Aspects Of The Feto-placental Interface In The Pregnancy Induced Hypertension

Background and aims We studied the feto-placental interface, in Pregnancy Induced Hypertension (PIH), to present his specific structural modifications. Method We have studied the microscopical modifications of 68 placentas obtained after delivery for two equal groups representing mothers with PIH and normotensive. The samples obtained by sections were specifically prepared for the study using three types of histological stains. We used optical microscopy for observing mainly the lumen of spiral arteriole and changes in its intimate and medial tunica. Results We registered the following specific structural modifications in the pregnancies with PIH : fibrosis in the middle of the villosity, fibrinoid necrosis, condensation of stromal connective tissue, syncytial layer agglutinations of the villous or intervillous spaces (nodes, buds, or bridges), thrombosis and/or infarction of the spiral vessels and villous capillary endothelial atheromatosis. Conclusions Our study was done to find a better understanding of the histo-logical changes of the preeclamptic feto-maternal interface concerning his role in PIH. The morphological modifications of the feto-placental interface in the PIH represent a marker of the fetal and postnatal hypoxia/ischemia with an immediate and late impact upon their cerebral development.

PO-0365 Histological Aspects Of The Feto-placental Interface In The Gestational Diabetes Mellitus

<h3>Background and aims</h3> We studied the feto-placental interface, in the Gestational diabetes mellitus (GDM), to present his specific structural modifications and his cellular injuries. <h3>Method</h3> An optical microscopic analysis was performed on 30 placentas, obtained after delivery for two equal groups representing mothers with GDM and normal pregnancies. The samples obtained by sections were specifically prepared for the study using three types of histological stains. The histological observation centred upon the: trophoblast, villous stroma and fetal capillary. The statistical study of the data was performed using SPSS 17.0. <h3>Results</h3> Through optical microscopy were identified varying degrees of lesions consisting of: villous oedema, proliferation and villous fibrosis of the capillaries, large number of syncytial knots, important fibrinoid necrosis, moderate fibrin thrombi, hyperplasia of the syncytiotrophoblast, chorangiosis, slightly thickened of the basement membrane of the feto-maternal interface. <h3>Conclusion</h3> Histological changes in the placentas of women with GDM are significant factors contributing to fetal anoxia with impact on placental vascular permeability. A diabetic milieu causes vascular dysfunction, increasing angiogenesis in GDM is considerred to be the cause of the placental abnormalities and complications (miscarriage, stillbirth, macrosomia, and congenital anomalies).

Placental expression of lipoprotein lipase and endothelial lipase in women with severe preeclampsia

Objective To investigate the effect of abnormal lipid metabolism in the pathogenesis of preeclampsia.Methods Thirty women with severe preeclampsia who delivered by cesarean section in the International Peace Maternity & Child Health Hospital from November 1,2011 to June 30,2012,were included as the study group.Thirty normal pregnant women delivered during the same period by cesarean section were included as the control group.The mRNA levels of lipoprotein lipase (LPL) and endothelial lipase (EL) in the placentas were quantified by real-time polymerase chain reaction.The expression of LPL/EL protein was detected by Western-blot assay and the distribution on the placenta was determined by immunohistochemical staining.The maternal serum level of lipid markers was detected by automatic biochemical analyzer.Difference between the two groups was compared with t-test or rank-sum test.Results (1) The triglyceride (TG) concentration [(3.35±0.80) mmol/L vs (2.75± 0.92) mmol/L,t =3.082,P=0.003] and atherosclerosis index (AI) (2.76±0.46 vs 2.47±0.34,t=3.066,P=0.003) increased in the study group compared with the control group,while the concentration of high-density lipoprotein-cholestrol (HDL-c) decreased[(1.64 ± 0.34) mmol/L vs (1.85 ± 0.22) mmol/L,t=-3.157,P =0.003].(2) The median level of LPL mRNA expression in placenta of the study group was higher than that of the control [1.26 (0.46-1.58) vs 0.52 (0.34-0.84),Z=-2.587,P=0.010],whereas the expression of EL mRNA was lower [0.65 (0.48-0.76) vs 1.32 (0.94-1.62),Z=-4.154,P=0.000].(3) Immunohistochemical analysis showed that the placenta EL and LPL located in cytoplasm of syncytiotrophoblast cells at the materno-placental interface and of endothelial cells at the feto-placental interface.(4) Compared with the control group,the median level of LPL protein expression in placenta inthe study group increased [0.68(0.46-0.83) vs 0.31(0.15-0.55),Z=3.335,P=0.001],and the expression of EL protein decreased [0.13 (0.11 0.16) vs 0.70(0.56 0.81),Z=-5.711,P=0.000].The expression of LPL protein was negatively correlated with that of EL protein (r=-0.501,P=0.000).Conclusions Abnormal lipid metabolism contributes to the pathogenesis of severe preeclampsia. Key words: Pre-eclampsia; Lipoprotein lipase; Endothelial lipase; Placenta

Dysregulation of Placental Endothelial Lipase and Lipoprotein Lipase in Intrauterine Growth-Restricted Pregnancies

Fetal supply of maternally derived fatty acids requires lipase-mediated hydrolysis of lipoprotein-borne triglycerides and phospholipids at the placental surface. The objective of the study was to test the hypothesis that members of the triglyceride lipase gene (TLG) family are expressed in the human placenta at the maternoplacental (syncytiotrophoblast) and fetoplacental (endothelial cells) interface and that their expression is altered in pregnancy pathologies. Expression of TLG family members in primary placental cells (trophoblast and endothelial cells) and tissues of first-trimester and term human placenta was analyzed by microarrays, RT-PCR, Western blotting, and immunohistochemistry. Their expression was compared between normal pregnancies and those complicated with intrauterine growth restriction (IUGR). Participants included women with uncomplicated pregnancies and pregnancies complicated by IUGR. Endothelial lipase (EL) and lipoprotein lipase (LPL) were the only lipases among the TLG family expressed in key cells of the human placenta. In first trimester, EL and LPL were expressed in trophoblasts. At term, EL was detected in trophoblasts and endothelial cells, whereas LPL was absent in these cells. Both lipases were found at placental blood vessels, EL in vascular endothelial cells and LPL in the surrounding smooth muscle cells. In total placental tissue EL expression prevails in first trimester and at term. Compared with normal placentas, EL mRNA was decreased (30%; P < 0.02), whereas LPL mRNA expression was increased (2.4-fold; P < 0.015) in IUGR. EL is the predominant TLG family member in the human placenta present at both interfaces. EL and LPL are dysregulated in IUGR.

Perinatal programming of appetite control by leptin?

The concept of fetal and perinatal programming of neuroendocrine functions has attracted growing interest within the last 15 years. Barker (1) first demonstrated the relationship between low birth weight and diseases of later adulthood such as coronary heart disease and the metabolic syndrome. Meanwhile, there is convincing evidence that intrauterine factors such as placental insufficiency lead to a change of the metabolic and endocrine milieu in the feto-placental interface. These changes influence birth weight and also lead to persistent remodelling of endocrine functions (2, 3). Perinatal programming, therefore, implies persistent epigenetic changes of primarily genetic neuroendocrine functions. Finding the underlying mechanisms for the perinatal programming of a disease such as the metabolic syndrome – a disease associated with tremendous socioeconomic consequences – would be the first step towards initiating innovative concepts for preventive measures. In a different but related field dealing with the early determination of neuroendocrine function needed later in life, namely the specification of sexually dimorphic patterns in the mammalian forebrain (4), recent advances have been made: specifically the surge of sex steroid secretion in early neonatal life has been linked to neuroanatomical and functional changes in the forebrain (5 – 7).

Harry Goldblatt Award 2002

HomeHypertensionVol. 41, No. 3Harry Goldblatt Award 2002 Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBHarry Goldblatt Award 2002 Originally published1 Mar 2003https://doi.org/10.1161/01.HYP.0000060144.52886.F7Hypertension. 2003;41:867–868The Harry Goldblatt Award is presented each year to the author(s) of the paper(s) from last year’s meeting judged by the Publication Committee of the Council for High Blood Pressure Research to represent the most significant new contribution to the understanding of the causes and/or consequences of hypertension. The award is named for the eminent hypertension researcher Dr Harry Goldblatt and is supported by a generous donation to the council from his family. Included with the award is a $1,000 honorarium and a commemorative plaque.Download figureDownload PowerPointDr Alberto Nasjletti (left), Dr Robin Davisson (center), Dr Ernesto Schiffrin (right).The 2002 Harry Goldblatt Award in Cardiovascular Research was awarded to Dr Robin Davisson, who is an assistant professor in the Department of Anatomy and Cell Biology at the University of Iowa College of Medicine. Dr Davisson has been using genetic approaches to study mechanisms of hypertension. She has been particularly interested in using novel transgenetic mouse models of brain-selective overexpression of the renin-angiotensin system to investigate central mechanisms of neurogenic hypertension. In an interesting extension of her expertise in the area of genetics, Dr Davisson has developed a spontaneous genetic mouse model of preeclampsia. For her manuscript entitled “Discovery of a Spontaneous Genetic Mouse Model of Preeclampsia,” Dr Davisson has been awarded the Harry Goldblatt Award in Cardiovascular Research.The mechanisms that account for preeclampsia, the most prevalent hypertensive disorder of pregnancy, are unclear. Research in this area has been impeded by the lack of experimental models to study this disorder. Dr Davisson had the clever idea that BPH/5 mice, an inbred mouse strain with mildly elevated arterial pressure, might develop a pregnancy-induced hypertensive syndrome. Using telemetry, Dr Davisson clearly demonstrated that BPH/5 mice, but not controls, exhibit a further increase in arterial pressure during the last trimester of pregnancy. As in human subjects with preeclampsia, the late gestational rise in arterial pressure returned to control levels shortly after delivery. During the last trimester of pregnancy, the hypertension was associated with proteinuria and progressive glomerulosclerosis, changes that resolved after delivery. The BPH/5 mice also delivered smaller litters and longitudinal ultrasound studies documented fetal demise before the onset of hypertension and renal disease. This latter observation supports a prominent hypothesis suggesting that the primary defect in preeclampsia originates at the fetoplacental interface. This animal model, which bears a close resemblance to clinical preeclampsia, would appear to provide a unique opportunity to study the molecular genetic pathophysiology of this disorder.Past Recipients of the Goldblatt Award2001Lilach O. Lerman, MD, PhD2000Jane F. Reckelhoff, PhD1999Craig H. Gelband, PhD1998Edward W. Inscho, PhD1997Kristof Graf, MDSandra Pfister, PhD1996Ryuichi Morishita, MD, PhD1995Dewan S.A. Majid, MD, PhD1994R. Davis Manning, Jr, PhD1993William J. Stekiel, PhD1992Albert P. Rocchini, MD1991Donald W. Ducharme, PhDDouglas W. Harris, MDJames H. Ludens, MDFrederic Mandel, MDW. Rodney Mathews, MD1990Pavel Hamet, MD, PhD1989John M. Hamlyn, PhD1988Albert J. Nasjletti, MD1987Victor J. Dzau, MD1986Willa A. Hseuh, MD1985Daniel T. O’Connor, MD1984John E. Hall, PhD1983Gaetan Thibault, PhD1982Gunner Gothberg, MD1981Michael J. Antonaccio, PhD1980Donald D. Heistad, MD1979Carlos Ferrario, MD Previous Back to top Next FiguresReferencesRelatedDetails March 2003Vol 41, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/01.HYP.0000060144.52886.F7 Originally publishedMarch 1, 2003 PDF download Advertisement

Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice.

Two uptake systems that control the extracellular concentrations of released monoamine neurotransmitters such as noradrenaline and adrenaline have been described. Uptake-1 is present at presynaptic nerve endings, whereas uptake-2 is extraneuronal and has been identified in myocardium and vascular and nonvascular smooth muscle cells. The gene encoding the uptake-2 transporter has recently been identified in humans (EMT), rats (OCT3), and mice (Orct3/Slc22a3). To generate an in vivo model for uptake-2, we have inactivated the mouse Orct3 gene. Homozygous mutant mice are viable and fertile with no obvious physiological defect and also show no significant imbalance of noradrenaline or dopamine. However, Orct3-null mice show an impaired uptake-2 activity as measured by accumulation of intravenously administered [(3)H]MPP(+) (1-methyl-4-phenylpyridinium). A 72% reduction in MPP(+) levels was measured in hearts of both male and female Orct3 mutant mice. No significant differences between wild-type and mutant mice were found in any other adult organ or in plasma. When [(3)H]MPP(+) was injected into pregnant females, a threefold-reduced MPP(+) accumulation was observed in homozygous mutant embryos but not in their placentas or amniotic fluid. These data show that Orct3 is the principal component for uptake-2 function in the adult heart and identify the placenta as a novel site of action of uptake-2 that acts at the fetoplacental interface.

Lupus nephritis and the anti-phospholipid antibody syndrome in pregnancy

Lupus nephritis and the anti-phospholipid antibody syndrome in pregnancy

Determination of cytokine mRNA-expression in term human placenta of patients with gestational hypertension, intrauterine growth retardation and gestational diabetes mellitus using polymerase chain reaction.

Our objective was to test the hypothesis, that pregnancy-related diseases are going along with changes in cytokine mRNA-expression at the placental site, either as a part of a pathological process or in connection with regulatory mechanisms induced by disturbances at the feto-maternal interface resulting from previous pathological changes--in the sense of counterregulation. The cytokines chosen for this investigation are known to 1.) be expressed in the human placental tissue, 2.) to be involved in immunological processes and 3.) the regulation of growth and differentiation processes of different cell types of the placenta or decidua, 4.) to play a role in the angiogenesis at the feto-placental interface and 5.) to be involved in pathological processes in other human diseases. 32 samples derived from term human placentas were examined for messenger RNA levels of interleukin 1 alpha (II-1 alpha), tumor necrosis factor-alpha (TNF-alpha), platelet derived growth factor-A chain (PDGF-A), platelet derived growth factor-B chain (PDGF-B), and platelet derived growth factor receptor (PDGF-R) using a semiquantitative reverse transcriptase (RT) polymerase chain reaction (PCR) protocol. To calibrate samples in our procedure, beta-actin mRNA (messenger ribonucleic acid) known as a "house keeping" gene was proven to be constantly expressed. The sample-groups consisted of normal pregnancies (n = 8), gestational hypertension (GH, n = 7), intrauterine growth retardation (IUGR, n = 6), gestational diabetes mellitus (GDM, n = 5), and gemini (n = 3 x 2). Throughout the 32 samples, a significant correlation between PDGF-A and PDGF-R expression, PDGF-A and TNF-alpha expression was stated (p = 0.007). Compared with the pattern of expression in normal placentas, placentas of growth retarded pregnancies had higher Il-1 alpha mRNA (p = 0.016), PDGF-A (p = 0.029) and PDGF-B (p = 0.001) levels. The samples of the gestational hypertension group and placentas of patients with gestational diabetes displayed a significantly stronger PDGF-R mRNA signal (p = 0.0029 and p = 0.008). Though these marked differences in cytokine mRNA levels between clinical groups were statistically proven, clear correlation of these differences with clinical data was not found.

Glutathione and Glutathione-related Enzymes in Decidua and Placenta of Controls and Women with Pre-eclampsia

Pre-eclampsia is a major complication of pregnancy with high morbidity and mortality rates. The aetiology is still unclear but impaired detoxification or enhanced levels of reactive (oxygen) metabolites may contribute to the development or maintenance of pre-eclampsia. Glutathione and glutathione-related enzymes, as one of the major detoxificating and free-radical scavenging systems, may play a role in controlling the disease.Seventeen normotensive pregnant women and 24 pre-eclamptic women were investigated prospectively with respect to placental and decidual levels of total glutathione (GSH), glutathione S-transferase activity (GST), selenium-dependent glutathione peroxidase (SeGPX) and total glutathione peroxidase activity (TGPX, both selenium- and non-selenium-dependent GPX). Decidual levels of glutathione and related enzymes were compared with placental levels, and the investigated parameters in pre-eclampsia were compared with those in normotensive pregnancy by the Mann–Whitney U -test. Clinical data were correlated with biochemical parameters by Spearman's correlation test.Glutathione levels were significantly higher in decidua as compared with placenta. Glutathione levels were elevated in pre-eclampsia and HELLP (haemolysis, elevated liver enzymes, low platelets) as compared to normotensive pregnancy for decidua and in the placenta of patients with pre-eclampsia only. Glutathione S-transferase activity was not different between the two groups. In the placenta of patients with pre-eclampsia+HELLP, total glutathione peroxidase activity was elevated versus controls. Selenium-dependent glutathione peroxidase activity was higher in decidua versus placenta and in decidua of pre-eclamptic versus control subjects.Enhanced glutathione concentrations and glutathione peroxidase activities were often found in placenta and decidua in pre-eclampsia, probably as a compensatory mechanism to prevent further damage by peroxides, (oxygen) radicals or other toxins in the placenta or in the feto–placental interface.

Ethanol-induced expression of cytokines in a first-trimester trophoblast cell line

OBJECTIVES: Altered cytokine expression at the fetoplacental interface may be a potential mechanism for the development of fetal immune dysfunction in children with fetal alcohol syndrome. This study was conducted to determine whether first-trimester trophoblasts respond to ethanol exposure by the induction of specific cytokines. STUDY DESIGN: HTR-8/SVneo trophoblast cells were cultured in vitro in the presence of either ethanol (0.5% [vol/vol]), lipopolysaccharide (1 μg/mL), or ethanol and lipopolysaccharide. Expression of granulocyte colony–stimulating factor, regulated on activation normal T cell expressed and secreted, and interleukin-6 was examined by Northern analysis and enzyme-linked immunosorbent assay. RESULTS: Culture in the presence of ethanol, lipopolysaccharide, or lipopolysaccharide and ethanol resulted in the increased transcription and secretion of granulocyte colony–stimulating factor, regulated on activation normal T cell expressed and secreted, and interleukin-6 at significantly greater levels ( P < .01) than control cultures. CONCLUSIONS: Human first-trimester trophoblasts express high levels of cytokines when cultured in the presence of ethanol. Trophoblasts may therefore be an important exogenous source of cytokines for the fetus, and altered cytokine levels during early gestation may have an adverse effect on the development of the fetal immune system. (Am J Obstet Gynecol 1998;179:470-5.)

Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction

Objectives: The factor V Leiden mutation is the most common genetic predisposition to thrombosis. However, little is known concerning the reproductive outcome of mutation carriers or prenatal expressivity of this thrombogenic mutation. Our purpose was to examine whether this mutation presents phenotypically as miscarriage or idiopathic placental thrombosis. Study design: We performed two studies. First, a case-control comparison to determine whether fetal or maternal carriers of the factor V Leiden mutation are at risk for spontaneous miscarriage was performed, and, second, a cohort study evaluating placental infarction in fetuses carrying this mutation was performed. Results: We found a twofold increase in the factor V Leiden carrier frequency in 12 of 139 (8.6%) abortuses compared with 17 of 403 (4.2%) unselected pregnant women seen in the labor and delivery suite and, even more remarkable, a tenfold increase in the fetal carrier frequency in 10 of 24 (42%) placentas with >10% placental infarction compared with 7 of 372 (1.9%) placentas with <10% placental infarction. Conclusions: These findings suggest a prenatal phenotype and effects of this mutation at the fetoplacental interface. If large prospective studies confirm these findings, then testing for this thrombogenic mutation should be considered in women and placental tissue from spontaneous abortuses and placentas with evidence of placental infarction. In addition to identifying individuals and families at risk for thrombosis, this information may help to improve our understanding of hemostasis and circulatory disturbances at the fetoplacental interface. (Am J Obstet Gynecol 1997;177:402-5.)

Presence of Activated Macrophages in a Murine Model of Early Embryo Loss

Even though our knowledge of the phenomenon at play at the fetoplacental interface has greatly advanced during the past years, a complete understanding of the reasons why the developing embryo is not rejected by maternal immune effector cells remains largely unknown. We have used immunohistochemistry with the macrophage-specific markers F4/80 and MHC II to study the relationship between decidual infiltration and resorption in murine models of embryo loss between days 6 and 10 of gestation. Analysis of day 8 CBA/J x DBA/2 pregnancies has revealed 2 distinct populations of embryos. The majority (69.4%) expressed low levels of F4/80+ cells, but a minority (30.6%) expressed much higher level of the macrophage marker. In FBA/J x BALB/c, most embryos (91.7%) expressed low numbers of F4/80+ cells. As earlier experiments established that products of activated macrophages (TNF-alpha and nitric oxide) were implicated in embryo loss in this model, the activation status of the F4/80+ macrophages was assessed through the cell surface expression of MHC II. Again, a similar association was established: 30.6% of the CBA/J x DBA/2 embryos were infiltrated by significantly more MHC II+ cells than the control CBA/J x BALB/c mating. Finally, when coordinate expression of F4/80, MHC II and CD11b was assessed, it was found that an embryo significantly infiltrated by cells bearing one of the 3 markers was also heavily infiltrated by cells bearing the 2 other markers. This study has shown that the augmented infiltration of the deciduum with maternal macrophages is an early event which precedes spontaneous abortion of the early embryo.