Fas and FasL expression in placentas complicated with intrauterine growth retardation with and without preeclampsia

Objective: To compare the level of Fas and FasL immunohistochemical expression in villous trophoblast (VT), extravillous trophoblast (EVT) cells, decidual cells (DC), endothelial cells (EC) of villous blood vessels and spiral arteries between the study groups of intrauterine growth retardation (IUGR) placentas with and without preeclampsia (PE).

Methods: The study included 17 placentas from pregnancies complicated by IUGR?+?PE and 17 placentas from pregnancies complicated by idiopathic IUGR (I-IUGR). Seventeen placentas from normal pregnancies served as a control group. CD31 was used to detect endothelial cells (EC). Immunohistochemical expression of Fas and FasL was assessed in all examined parts of placenta using the semi-quantitative HSCORE method.

Results: FasL expression was significantly higher in all examined parts of placenta in I-IUGR as compared to IUGR?+?PE and control group. Placentas with IUGR?+?PE had the significantly lowest expression of FasL in VT and EC of villi vessels. Expression of Fas did not differ significantly between the study groups.

Conclusion: Different expression of FasL in placentas from I-IUGR and IUGR?+?PE suggests that FasL probably has a different role in the etiology of these two syndromes.     

Placental expression of insulin-like growth factor-I,fibroblast growth factor-basic,and neural cell adhesion molecule in preeclampsia

Objective. To investigate placental expression of insulin-like growth factor-I (IGF-I), fibroblast growth factor-basic (FGF-b), and neural cell adhesion molecule (N-CAM) in preeclampsia.

Study design. An immunohistochemical analysis using IGF-I, FGF-b, and N-CAM antibodies was conducted on 4% paraformaldehyde-fixed placental tissues of preeclamptic patients (N = 14) and normotensive pregnant subjects (N = 10). Immunostaining patterns of chorionic villi and amniochorionic membranes were assessed.

Results. Significantly increased FGF-b and N-CAM immunoreactivities in cytotrophoblasts and increased FGF-b immunoreactivity in capillary endothelium of chorionic villi of preeclamptic subjects were noted. Significantly increased FGF-b and decreased N-CAM immunoreactivities in extravillous trophoblasts and decidual cells of amniochorionic membranes obtained from preeclamptic subjects were demonstrated. Additionally, a significantly increased IGF-I immunoreactivity was shown in decidual cells of preeclamptic cases.

Conclusion. Investigation of the regional distribution of IGF-I, FGF-b, and N-CAM at the maternal–fetal interface establishes a better understanding of cell-specific altered growth processes, which may be associated with the pathogenesis of preeclampsia.     

Risk factors of intrauterine growth retardation in Congo

A case-control study was performed between April 1st and September 30th to investigate determinants of intrauterine growth retardation (IUGR) in 3 centers in Brazzaville, Congo. Each patient group included 539 neonates. Cases were newborns with birth weight below the 10th percentile of the Leroy and Lefort curve. Risk factors of IUGR identified with univariate analysis were: maternal age<20 years, low educational level, unmarried woman, low social and economic status, primiparity, low birthweight of previous child, low interpregnancy interval, number of prenatal examinations<4, maternal weight gain during pregnancy<5kg and malaria. Multivariate analysis retained 3 risk factors: low educational level, low social and economic status, and maternal weight gain during pregnancy<5kg. This study enabled us to identify certain risk factors of IUGR useful for establishing a prevention strategy.     

Fibrinolytic parameters in normotensive pregnancy with intrauterine fetal growth retardation and in severe preeclampsia

In pregnancy a decrease in fibrinolytic activity, which is due to an increase in plasminogen activator inhibitor activity and plasminogen activator inhibitor type 1 and type 2, has been described. Because the placenta is a source of both type 1 and type 2 plasminogen activator inhibitor, we have studied them and other fibrinolytic parameters in a group of normotensive pregnant women with intrauterine fetal growth retardation and in two groups of women with preeclampsia, with or without intrauterine growth retardation. A significant increase in plasminogen activator inhibitor type 1 antigen and plasminogen activator inhibitor activity was observed in preeclampsia, with or without intrauterine growth retardation, but not in normotensive pregnancy with intrauterine growth retardation, when compared with normal pregnancy. Plasminogen activator inhibitor type 2 antigen levels showed a significant decrease in both groups of pregnant women (normotensive or preeclamptic) with intrauterine growth retardation when compared with pregnancies without intrauterine growth retardation. A significant correlation between plasminogen activator inhibitor type 2 levels and fetal weight has been observed in the clinical groups.     

子痫前期及ＨＥＬＬＰ综合征引产问题

通过综述1980至今发表的临床研究,探讨子痫前期和HELLP综合征(HELLP综合征为妊娠期高血压疾病的严重并发症,本病以溶血、肝酶升高及血小板减少为特点)的引产问题,包括如何评估25～34周及<25周的子痫前期、HELLP综合征的病情及终止妊娠指征,终止妊娠的方式及终止妊娠对于母儿的风险和益处,为临床提供循证医学证据。     

Oligohydramnios,intrauterine growth retardation and fetal death due to umbilical cord torsion

Intrautrine fetal death was observed in a woman at 35 gestational weeks shortly after she was admitted to hospital due to suspected placental insufficiency expressed by oligohydramnios and fetal growth retardation. The pathologic examination showed umbilical cord torsion and an organized thrombus at the site of the torsion. This findings could imply that both the fetal death and the placental insufficiency were the results of the cord torsion.affiliated to the Medical School of the Hebrew University and Hadassa, Jerusalem Correspondence to: A. Ben-Arie     

Placental gene expression patterns of epidermal growth factor in intrauterine growth restriction

Objective

In this study, we compared human placental gene expression patterns of epidermal growth factor (EGF) in pregnancies with intrauterine growth restriction (IUGR) vs. normal pregnancies as control.

Study design

Gene expression of EGF was determined from human placental samples collected from all pregnancies presenting with IUGR at our institution during the study period January 1, 2010–January 1, 2011. Multiple clinical variables were also assessed including maternal age, gestational weight gain, increase of BMI during pregnancy and fetal gender.

Results

A total of 241 samples were obtained (101 in the IUGR pregnancy group, 140 in the normal pregnancy group). EGF was found to be underexpressed in the IUGR group compared to normal pregnancy (Ln2^α: −1.54; p < 0.04). Within the IUGR group no fetal gender-dependent difference was seen in EGF gene expression (Ln2^α: 0.44; p < 0.06). Similarly, no significant difference in EGF expression was noted in cases with more vs. less severe forms of IUGR (Ln2^α: −0.08; p = 0.05). IUGR pregnancies were significantly more common in the maternal age group 35–44 years compared to other age groups. Gestational weight gain and gestational BMI increase were significantly lower in IUGR pregnancies compared to controls.

Conclusions

Placental expression of EGF was found to be reduced in IUGR pregnancies vs. normal pregnancies. This may partly explain the smaller placental size and placental dysfunction commonly seen with IUGR. An increased incidence of IUGR was observed with maternal age exceeding 35 years. The probability of IUGR correlated with lower gestational weight gain and lower BMI increase during pregnancy.     

The value of Doppler assessment of the uteroplacental circulation in predicting preeclampsia or intrauterine growth retardation

Flow velocity waveforms of the uteroplacental arteries were analyzed at 20 and 24 weeks of gestation, by means of duplex pulsed Doppler ultrasonography, in 93 women at risk for preeclampsia or intrauterine growth retardation. The ability of an elevated resistance index to predict these conditions was tested. At 20 and 24 weeks an abnormal resistance index was significantly associated with intrauterine growth retardation but not with preeclampsia, with or without proteinuria. A low fetal abdominal circumference at 20 or 24 weeks or an increasing maternal plasma uric acid concentration at 24 weeks was as predictive as an elevated resistance index. In a second group of 43 women, screened in the same way, the only association was of an elevated resistance index at 20 weeks with intrauterine growth retardation. Although elevated resistance indices occur more commonly in women who develop intrauterine growth retardation and/or preeclampsia, the correlation is not close enough to be clinically useful as a screening test.     

Mast cells, histamine and development of the placental vascular network in pregnancies complicated by preeclampsia and intrauterine growth retardation

Importance of angiogenesis in proper development of placenta is unquestioned. Abnormalities in vascular development are typical for complications of pregnancy: intrauterine growth retardation (IUGR) and preeclampsia (PE). As mast cells are involved in new vessels sprouting and development we tried to disclose if they can be involved in etiology or pathogenesis of IUGR and/or PE. MATERIAL AND METHODS: Placentas from PE-complicated pregnancies (n=11), IUGR-complicated pregnancies (n=10), and from healthy women--controls (n=13) were obtained after cesarean sections. Histamine concentration was measured and immunohistochemical staining for mast cell tryptase was performed. Microscopic slides of placental tissue were analyzed with morphometric software. RESULTS: We disclosed increased histamine concentration in PE group--227.3 +/- 17.7 (in ng of histamine per 1 g of tissue) and decreased concentration in IUGR group 114.3 +/- 13.5 vs control--178.1+/- 18.9. Histamine concentration corresponded with density of mast cells in examined groups: PE group--8.32 cells/mm2 +/- 1.3, IUGR--3.07 +/- 1.05 and control--5.14 +/- 1.2. The mean area of mast cells identified in PE as well as in IUGR group was smaller than the mean area of mast cells in controls. V/EVT index was decreased in PE and IUGR group in comparison to controls, respectively: 0.15 +/- 0.018; 0.12 +/- 0.014; 0.23 +/- 0.029. CONCLUSIONS: We suggest that differences in mast cells density and corresponding differences in histamine concentration are associated with pathogenesis of PE and IUGR or are consequence of primary cause.     

PAPP-A levels of late pregnancy in preeclampsia and HELLP syndrome

Purpose  

To determine the relationship between pregnancy-associated plasma protein-A (PAPP-A) levels and preeclampsia and HELLP syndrome at last trimester and to investigate if the severity of preeclampsia would be associated with PAPP-A levels.     

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction

Objective: We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR.

Methods: During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression.

Results: There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2^α: 0.92; p?α: 0.72; p?=?0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2^α: ?1.49; p?Conclusion: We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.     

Vascular endothelial growth factor, its receptors, and the tie receptors in the placental bed of women with preeclampsia, diabetes, and intrauterine growth retardation

Placental bed vascular function is compromised in pregnancies complicated by preeclampsia (PE), intrauterine growth retardation (IUGR), and maternal diabetes mellitus (DM). We performed an immunohistochemical analysis of vascular endothelial growth factor (VEGF), its receptors (VEGFR) -1 and -2, and the Tie-1 and -2 receptors in cryostat tissue sections of the placental bed from healthy women (n = 5) and women with PE (n = 5), IUGR (n = 5), and DM (n = 5). VEGF immunoreactivity was stable between the study groups. VEGFR-1 immunoreactivity in the myometrial vascular smooth muscle cells was strongest in the controls. In the myometrial cells, the strongest VEGFR-2 immunoreactivity was seen in women with IUGR. In the decidual vascular endothelial cells, the strongest Tie-1 immunoreactivity was observed in healthy women and in those with DM. Alterations in the placental bed expression of VEGFR-1, VEGFR -2, and Tie-1, but not of VEGF and Tie-2, may be associated with PE, IUGR, or DM.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation

Objectives.?The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies.

Patients and methods.?The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method.

Results.?There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood.

Conclusions.?It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

Placental expression of PHLDA2 in selective intrauterine growth restriction in monozygotic twins

Studies have showed that increase of placental expression of imprinted genes PHLDA2 may have a potential regulatory role in fetal IUGR (intrauterine growth restriction) in singleton. In this study, we investigate the expression level of PHLDA2 in placenta of monozygotic twins (MZT) with selective intrauterine growth restriction (sIUGR) and normal MZT. Both mRNA levels and protein levels of PHLDA2 were signi?cantly increased in placenta sharings of small fetus in cases of sIUGR. Our results suggest upregulated PHLDA2 in placenta may be associated with the pathogenesis of sIUGR.     

Placental expression of nitric oxide synthase during HELLP syndrome: the correlation with maternal-fetal Doppler velocimetry

BACKGROUND: To correlate Doppler waveform of the uterine and umbilical vessels to placental nitric oxide synthase (NOS) expression in pregnant women with HELLP (hemolysis, elevated liver enzymes, low platelets count) syndrome. METHODS: mRNA expression of inducible NOS (iNOS) and endothelial NOS (eNOS) was assessed, after cesarean section, in placental samples from 10 women affected by HELLP syndrome and 10 controls. Pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries were measured. RESULTS: iNOS expression was significantly lower in placenta from women with HELLP syndrome than controls. When comparing the results with Doppler flow measurements, we found a negative correlation between umbilical pulsatility index and eNOS expression (r = -0.91) and a positive correlation with iNOS expression (r = 0.86). CONCLUSIONS: The reduced iNOS expression in women with HELLP syndrome may indicate the extreme placental dysfunction that is unable to compensate for the endothelial derangement and related hypertension in spite of trying to improve fetoplacental perfusion and the delivery of nutrients to the fetus.