Proliferation of villous trophoblast and stroma in normal and pathologic pregnancies (preeclampsia)

Pregnancies, complicated with preeclampsia, present with intrauterine growth retardation of the fetus and small (in size and weight) placentas. The present study aims at establishing the expression of proliferative nuclear antigen Ki-67 in the villous trophoblast and stroma, and to compare the results between study (preeclamptic cases n = 30) and control (normal n = 30) groups. The number of Ki-67 positive nuclei both in the preeclamptic trophoblast and stroma significantly increases those of the controls. Our results show that the defect in the development of the placenta in preeclampsia is not associated with low proliferative potential.     

Evaluation of the maternal and umbilical vein serum sFas/sFasL system in pregnancies complicated by preeclampsia with intrauterine growth retardation

OBJECTIVE: The aim of this study was to determine the maternal and umbilical vein soluble Fas and its ligand (sFasL) serum levels in pregnancies complicated by preeclampsia with intrauterine growth retardation (IUGR). PATIENTS AND METHODS: The study was carried out on 11 preeclamptic delivering patients in the third trimester of pregnancy with severe preeclampsia complicated by intrauterine growth retardation. The control group consisted of 12 healthy normotensive delivering patients with singleton uncomplicated pregnancies, without any renal, heart and vascular diseases and with normal laboratory tests. Maternal and umbilical serum soluble Fas and FasL concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Increased maternal and umbilical vein serum sFas and increased umbilical vein serum sFasL levels were found in the study group in comparison with the control group. In our study in both groups of patient higher maternal sFas values were observed in comparison with the umbilical cord blood. Further studies are necessary to evaluate the role of Fas/FasL pathway in pregnancies complicated by preeclampsia and intrauterine growth retardation.     

先兆子痫患者母胎界面上细胞凋亡的研究

目的:研究先兆子痫患者母胎界面上细胞凋亡水平及凋亡相关分子的表达变化。方法:分别收集妊娠25、27、29、30和31周及足月分娩的正常妊娠者和先兆子痫患者的胎盘组织,采用脱氧核糖核酸末端转移酶介导的dUTP刻痕末端标记法(TUNEL)检测母胎界面上细胞凋亡情况, 并行凋亡细胞定位;RT-PCR检测正常妊娠和先兆子痫胎盘组织中P53,Bcl-2和Bax的mRNA表达水平的差异。结果:正常妊娠和先兆子痫患者胎盘中发生凋亡的细胞数目都随孕周延长而逐渐增高,但先兆子痫的胎盘中细胞凋亡率明显高于正常妊娠者;正常妊娠胎盘中凋亡细胞主要为合体滋养层细胞,足月胎盘绒毛内血管内皮细胞亦有少量细胞凋亡,而先兆子痫胎盘中细胞滋养层细胞、合体滋养层细胞和绒毛内血管内皮细胞均发生明显的凋亡;RT-PCR显示先兆子痫胎盘组织中P53和Bax的mRNA水平明显高于同期妊娠的正常胎盘,而Bcl-2水平显著降低。结论:正常妊娠过程中胎盘组织中只在有限部位出现少量细胞凋亡,而先兆子痫胎盘组织中细胞过度凋亡, 且凋亡细胞分布广泛,并伴有凋亡相关分子的表达上调。表明先兆子痫的发生与胎盘组织中滋养层细胞大量凋亡密切相关。     

Superoxide dismutase activity in normal and preeclamptic placentas

OBJECTIVES: A deficiency in superoxide dismutase (SOD) activity in preeclamptic placentas can lead to an excess of superoxide radicals and may be responsible for the development and the severity of preeclampsia (PE). DESIGN: Our studies were undertaken in order to determine placental SOD activity and to investigate their association with the development and the severity of PE. MATERIALS AND METHODS: The activity of SOD was determined using a spectrophotometric method in 22 placentas from normal term pregnancies (group K), 24 placentas from pregnancies complicated by severe PE (group PE), and 21 placentas from pregnancies complicated by severe PE and intrauterine growth retardation (IUGR) (group PEI). RESULTS: Mean activity of SOD (MSOD) in 45 preeclamptic placentas 3.89 +/- 1.32 (M +/- SD) was significantly lower (P = 0.008) as compared to MSOD in the group K (6.75 +/- 1.96). MSOD in the PEI group (3.5 +/- 1.29) was significantly lower (P = 0.03) as compared to MSOD in the group K. MSOD in the PE group (4.23 +/- 1.25) was lower than MSOD in the group K, but this difference was not statistically significant (P = 0.11). MSOD in the group PEI was lower as compared to MSOD in the PE group, however this difference was not statistically significant (P = 0.23). CONCLUSIONS: The studies revealed decreased SOD activity in preeclamptic placentas in comparison to normal placentas.     

Maternal and Umbilical sTNF-R1 in Preeclamptic Pregnancies with Intrauterine Normal and Growth Retarded Fetus

Objective: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). Patients and Methods: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). Results and Conclusions: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFα and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.     

Maternal and umbilical sTNF-R1 in preeclamptic pregnancies with intrauterine normal and growth retarded fetus.

OBJECTIVE: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). PATIENTS AND METHODS: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.     

Histomorphometry of the human placenta in maternal preeclampsia

The placentas of five mothers with severe preeclampsia who gave birth to moderately growth-retarded term infants were compared to a group of placentas collected from mothers who had uncomplicated pregnancies and normal term infants who were appropriate for gestational age. This study demonstrated that, on a quantitative histologic basis, the placentas of the preeclamptic mothers were morphologically very similar to the control placentas in terms of weight, parenchymal and cellular content, and surface areas of exchange between mother and fetus. The findings of this study support the hypothesis that, in preeclampsia not associated with severe intrauterine growth retardation, the perinatal morbidity associated with this condition is probably related more to some alterations in uteroplacental and, possibly, umbilical blood flows than to significant changes in placental structure and function. This may be due to compensatory repair mechanisms and extensive functional reserve capacities in these placentas.     

Expression of galectin-1, -3 (gal-1, gal-3) and the Thomsen-Friedenreich (TF) antigen in normal, IUGR, preeclamptic and HELLP placentas

BACKGROUND: Galectin-1 (gal-1) and galectin-3 (gal-3), which are members of the mammalian beta-galactoside-binding proteins, recognise preferentially (Galbeta1-4GlcNAc) sequences of several cell surface oligosaccharides. In addition, gal-1 also binds to the Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc-). MATERIALS AND METHODS: Slides of frozen and paraffin-embedded placental tissue of patients with fetal intrauterine growth retardation (IUGR), preeclampsia, haemolysis, elevated liver enzymes, low platelets (HELLP) and normal term placentas were incubated with monoclonal and polyclonal antibodies against gal-1, gal-3 and TF. Staining reaction was performed with the avidin-biotinylated peroxidase complex (ABC) reagent. The intensity of the immunohistochemical reaction on the slides was analysed using a semi-quantitative score. The identity of galectin-expressing cells was analysed by using a double immunofluorescence method. RESULTS: We demonstrated immunohistochemically that the expression of gal-1 and gal-3 on the extravillous trophoblast (EVT) is significantly up-regulated in preeclamptic and HELLP placentas and unchanged compared with normal controls in IUGR placentas. The expression of the TF antigen is significantly up-regulated in IUGR and preeclamptic extravillous trophoblast cells and unchanged in HELLP placentas compared with normal controls. In addition, the expression of gal-1 is significantly up-regulated in the decidual tissue of preeclamptic placentas and in the villous trophoblast tissue of HELLP placentas. CONCLUSION: Our data showed that gal-1, gal-3 and TF were up-regulated on the membrane of EVT in preeclamptic placentas. In addition, the expression of gal-1 is significantly up-regulated in decidual tissue of preeclamptic placentas and villous trophoblast tissue of HELLP placentas. Taking into consideration the results of this study, we speculate that expression of both galectins and TF on the membrane of preeclamptic EVT and up-regulation of gal-1 in preeclamptic decidual cells may at least in part compensate for the apoptotic effects of maternal immune cells.     

DNA adducts level in normal and preeclamptic placentas

OBJECTIVE: An increase in lipid peroxidation intensification in preeclamptic placentas leads to an increased level of lipid peroxidation products and increased reactive oxygen species activity which can be associated with increased activation of chemicals to electrophilic species that bind covalently to DNA and form adducts. DESIGN: The aim of the study was the determination of DNA adducts (A-DNA) in placentas from normal and preeclamptic pregnancies. MATERIALS AND METHODS: The investigations comprised placentas obtained immediately after delivery from 21 normal pregnancies [group K], 24 pregnancies complicated by severe preeclampsia-PE without intrauterine growth restriction (IUGR [group PE] and 21 pregnancies complicated by severe PE and IUGR [group PEI]. DNA adducts were determined using nuclease P1 digestion enhancement version of the 32P-postlabeling method. The results were expressed in numbers of DNA adducts per 10(8) nucleotides. Comparative analysis was performed using ANO-VA and median tests. RESULTS: Mean level of A-DNA (MA-DNA) in the group PE--1.39 +/- 1.21 (M +/- SD) was similar (p = 0.57) to MA-DNA in group K (1.16 +/- 1.03). However MA-DNA in the PEI group (1.93 +/- 1.28) was significantly higher (p = 0.045) than MA-DNA in the group K as well as MA-DNA in the group PE (p = 0.025). MA-DNA level in all studied preeclamptic placentas (groups PE + PEI) was 1.65 +/- 1.26 and was similar (p = 0.152) to revealed in group K. CONCLUSIONS: The level of DNA adducts in placentas from pregnancies complicated by severe preeclampsia and IUGR is higher than in placentas from pregnancies complicated by severe preeclampsia without IUGR and higher than in placentas from normal pregnancies.     

Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus.

OBJECTIVE: The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients. PATIENTS AND METHODS: The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental-fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

Placental apoptosis in preeclampsia

OBJECTIVE: To determine whether preeclampsia is associated with an increase in placental apoptosis and differential expression of mediators of apoptosis. METHODS: Placental samples from 31 preeclamptic women and 31 normotensive controls were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining. Expression of Fas, Fas ligand, Bcl-2, and Bax was assessed using immunohistochemistry. RESULTS: The median percent apoptotic nuclei was significantly higher for the study group than for the controls (0.49 versus 0.19; P =.001), as was the median percent apoptotic nuclei in the trophoblast nuclei (0.33 versus 0.09; P <.01). Fas ligand expression was significantly less and Fas expression significantly greater in the villus trophoblast among the study subjects compared with controls. There was no difference in the expression of Bax or Bcl-2 between groups. CONCLUSION: Placental apoptosis and altered expression of Fas and Fas ligand in trophoblast might influence pathogenesis or sequelae of preeclampsia.     

Assessment of lipid peroxidation intensification in normal and preeclamptic placentas

OBJECTIVE: Free radical induced lipid peroxidation (LP) in the placenta has been suggested as a possible pathogenetic factor of preeclampsia (PE). DESIGN: The aim of the study was to assess LP intensification by the measurement of lipid peroxidation products (LPP) content in placentas from normal and preeclamptic pregnancies. MATERIALS AND METHODS: The investigations comprised placentas obtained immediately after delivery from 24 normal pregnancies [group K], 26 pregnancies complicated by severe PE without intrauterine growth restriction (IUGR) [group PE] and 23 pregnancies complicated by severe PE and IUGR [group PEI]. LPP content was measured by the quantitative determination of thiobarbituric acid reactive substances (TBA-RS) amounts in studied placentas. Used TBA test was calibrated with malondialdehyde (MDA) and results were expressed as MDA equivalent in nmol/mg protein. Comparative analysis was performed using U Mann-Whitney and median tests. RESULTS: Mean placental level of LPP (MLPP) in the group PE-2.45 +/- 0.39 (M +/- SD) was significantly higher (p < 0.001) as compared to MLPP in the group K (1.58 +/- 0.24). MLPP in the PEI group (2.81 +/- 0.65) was higher (p < 0.001) than MLPP in the group K as well as MLPP in the group PE but statistical significance of the latter difference was lower (p = 0.032). CONCLUSIONS: The intensification of LP in placentas from pregnancies complicated by severe PE is IUGR dependent and higher than in placentas from normal pregnancies. Obtained results may indicate that higher degree of LP intensification in preeclamptic placentas may be involved in PE pathogenesis.     

Expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human preeclamptic placenta: possible implications in the process of trophoblast apoptosis

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was originally identified as a receptor for oxidatively modified low-density lipoprotein. It has been reported that oxidative stress and hyperlipidemia play important roles in the etiology of preeclampsia, and that placental oxidative stress may stimulate syncytiotrophoblast apoptosis in preeclampsia. In this study, we examined the expression of LOX-1 in the human placentas of normal pregnancies and in preeclampsia using immunohistochemistry and Western blot analysis, and proposed that LOX-1 has a role in trophoblast apoptosis. To analyze apoptotic activity, the expression of the specific caspase cleavage site within cytokeratin 18 was assessed immunohistochemically using the monoclonal antibody M30 CytoDeath. Both LOX-1 and M30 immunoreactivity occurred predominantly in syncytiotrophoblasts. A significantly higher number of LOX-1 and M30-positive cells were found in preeclamptic placentas than in normal placentas. The number of M30-positive cells correlated with the apoptotic index of trophoblasts determined by TdT-mediated dUTP nick-end labeling (TUNEL). Syncytiotrophoblasts showing apoptotic activity were immunopositive to LOX-1 by double immunohistochemical fluorescence. We suggest that the functional role of syncytiotrophoblasts in placental dysfunction results from the localization and upregulation of LOX-1 in the preeclamptic placenta, possible implications in upregulation of syncytiotrophoblast apoptotic activity in preeclampsia.     

Alteration of vascularization in preeclamptic placentas measured by three-dimensional power Doppler ultrasound

Abstract

Objective: To evaluate the alteration of vascularization in preeclamptic placentas measured by three-dimensional (3D) power Doppler ultrasound.

Methods: We performed a prospective study of placental vascularization and placental volume in 27 singleton pregnancies complicated by preeclampsia and 41 normal pregnancies from 27 to 39 weeks of gestation. The placental volume was analyzed using the VOCAL imaging analysis program and 3D power histogram was used to calculate the placental vascular indices including vascularization index (VI), flow index (FI) and vascularization flow index (VFI).

Results: Of the 27 preeclamptic pregnancies, 9 were complicated by intrauterine growth restriction and 15 were severe preeclampsia. Furthermore, nine of the preeclamptic pregnancies had abnormal end diastolic flow in the umbilical artery. No significant correlation was noted between the placental vascular indices and gestational age in normal pregnancies. The placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls (VI, p?<?0.001; FI, p?=?0.022; VFI, p?<?0.001). Preeclamptic placental volume was also decreased compared with that of the controls (p?=?0.002). After adjustment for confounding factors, significant differences were observed in VI and placental volume. However, no correlation was found between 3D power Doppler vascular indices and umbilical artery flow velocities, and neither intrauterine growth restriction nor the severity of preeclampsia could be predicted by the vascular indices.

Conclusion: VI and placental volume are reduced in preeclamptic placenta. Placental vascular indices using 3D power Doppler ultrasound provide insights of placental vascularization in preeclampsia.     

Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome

OBJECTIVE: BNip3 and its homologue Nix are pro-apoptotic factors of the Bcl-2-family and are expressed in malignant tumors. In vitro, this expression was shown to be mediated by hypoxia. Recently, it has been shown that placental hypoxia as well as apoptosis are pathogenetic factors for pregnancy-induced hypertensive diseases and intrauterine growth retardation (IUGR). The aim of the study was to analyze placental expression of BNip3 and Nix in pregnancies complicated by preeclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and IUGR. MATERIAL AND METHODS: Placental tissue was sampled from 10 pregnancies each with preeclampsia, HELLP syndrome, IUGR and gestational age-matched controls. The placental expression of BNip3/Nix has been investigated with immunohistochemistry by the use of specific human BNip3/Nix antibodies. RESULTS: In cytotrophoblastic cells, the BNip3 expression was strong in the control placentas, but only mediate in the placentas from pregnancies with preeclampsia, IUGR or HELLP syndrome. The intensity of the Nix staining showed a similar pattern. In the syncytiotrophoblast, there was a weak BNip3 staining observable in the control as well as IUGR samples, whereas BNip3 was undetectable in preeclamptic placentas or those with HELLP syndrome. For Nix, only in the preeclampsia a weak staining was detectable, whereas all other probes were negative. CONCLUSIONS: Our study shows for the first time that the pro-apoptotic proteins BNip3 and Nix are expressed in the human placenta. Pregnancies with placental dysfunction and hypertensive pregnancy disorders with different clinical manifestations are characterized by a significantly decreased expression of BNip3 and Nix. These results suggest that the hypothesis of generally increased placental apoptosis in pregnancy-induced hypertensive disorders caused by disturbed trophoblast invasion has to be partly reconsidered.     

Catalase activity in normal and preeclamptic placentas

OBJECTIVE: The decrease of placental catalase (CAT) activity may lead to an increase of placental amounts of reactive oxygen species and can contribute to preeclampsia pathogenesis. DESIGN: The aim of the study was to determine CAT activity in placentas from normal and preeclamptic pregnancies (with and without intrauterine growth restriction--IUGR). MATERIALS AND METHODS: The investigations comprised placentas obtained immediately after delivery from 22 normal pregnancies (group K), 26 pregnancies complicated by severe preeclampsia-PE without IUGR (group PE) and 23 pregnancies complicated by severe PE and IUGR (group PEI). The activity of CAT was determined using a spectrophotometric method and expressed as IU/mg protein. Comparative analysis was performed using U Mann-Whitney test. RESULTS: Mean activity of CAT (MCAT) in the PEI group--0.38 +/- 0.14 (M +/- SD), was significantly lower (p < 0.001) as compared to MCAT in the group K (0.55 +/- 0.16). MCAT in the PE group (0.48 +/- 0.14) was lower than MCAT in the group K, but this difference was not statistically significant (p > 0.05). MCAT in the group PEI was significantly lower (p = 0.026) as compared to MCAT in the PE group. CONCLUSIONS: The activity of CAT is decreased in placentas from pregnancies complicated by severe PE and IUGR. Obtained results may indicate that the decrease of placental CAT activity may be involved in pathogenesis of IUGR in preeclamptic pregnancies.     

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.     

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.     

Evaluation of maternal and umbilical serum TNFα levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus

Objective.?The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFα serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients.

Patients and methods.?The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFα concentrations were estimated using a sandwich ELISA assay.

Results and conclusions.?Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFα levels than those in the normotensive controls. Our findings and other reports indicate that TNFα may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor α (TNFα) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental–fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

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.