Glutathione peroxidase activity in normal and preeclamptic placentas

OBJECTIVE: The decrease of placental glutathione peroxidase (GSH-Px) activity may lead to exacerbation of lipid peroxidation in preeclamptic placentas. DESIGN: The aim of the study was the determination of GSH-Px activity in placentas from normal and preeclamptic pregnancies (with and without intrauterine growth retardation-IUGR). MATERIALS AND METHODS: The investigations comprised placentas obtained immediately after delivery from 24 normal pregnancies (group K), 26 pregnancies complicated by severe preeclampsia-PE (group PE) and 23 pregnancies complicated by severe PE and IUGR (group PEI). The activity of GSH-Px was determined using a spectrophotometric method and expressed as IU/g protein. Comparative analysis was performed using u Mann-Whitney test. RESULTS: Mean activity of GSH-Px (MGSH-Px) in the PEI group--5.38 +/- 1.59 (M +/- SD), was significantly lower (p < 0.001) as compared to MGSH-Px in the group K (7.22 +/- 1.21). MGSH-Px in the PE group (6.47 +/- 1.31) was lower than MGSH-Px in the group K, but this difference was not statistically significant (p > 0.05). MGSH-Px in the group PEI was significantly lower (p = 0.023) as compared to MGSH-Px in the PE group. CONCLUSIONS: The activity of GSH-Px is decreased in placentas from pregnancies complicated by severe PE and IUGR. Received results may indicate that the decrease of placental GSH-Px activity may be involved in pathogenesis of IUGR in preeclamptic pregnancies.     

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.     

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.     

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.     

Circulating and placental endoglin concentrations in pregnancies complicated by intrauterine growth restriction and preeclampsia

Inadequate trophoblast invasion and spiral artery remodeling leading to poor placental perfusion and hypoxia are believed to underlie preeclampsia (PE) and intrauterine growth restriction (IUGR). Recent studies implicate increased circulating endoglin as a contributor to the pathogenesis of PE. The objective of this study was to determine whether placental and circulating endoglin concentrations are altered in pregnancies complicated by intrauterine growth restricted (IUGR) infants and to address the role of hypoxia on the regulation of placental endoglin. We analyzed 10 placentas each from normal pregnant (NP), PE, and IUGR subjects. Endoglin levels were 2.5-fold higher in preeclamptic placentas compared to NP (15.4+/-2.6 versus 5.7+/-1.0, p<0.01). In contrast, endoglin levels were similar in NP and IUGR placentas (5.7+/-1.0 vs 5.9+/-1.1, p=NS). Placentas from pregnancies with both PE and IUGR exhibited endoglin levels comparable to the PE group and significantly different from normotensive pregnancies with and without IUGR pregnancies (mean 14.9+/-4.0, n=9, p=0.013). Soluble endoglin concentrations in maternal plasma were comparable in NP and IUGR, but higher in women with PE (n=10 per group, p<0.05). Despite a 2-fold increase in hypoxia inducible factor, HIF-1alpha, we did not observe endoglin upregulation in NP, PE, or IUGR placental villous explants exposed to hypoxia (2% oxygen). In contrast to PE, placental or circulating endoglin is not increased in normotensive women delivering small, asymmetrically grown (IUGR) infants at term. The placentas of women with IUGR appear to be fundamentally different from PE women with respect to endoglin, despite the proposed common pathology of deficient trophoblast invasion/spiral artery remodeling and poor placental perfusion.     

Fetoplacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human placental cotyledon

OBJECTIVE: The purpose of this study was to evaluate fetoplacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. STUDY DESIGN: Two cotyledons from each placenta were selected from preeclamptic (n=8) and normotensive (n=7) pregnancies. In one cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10(-10)mol and 10(-11.5) mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. RESULTS: Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P=.02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P<.01), but not in normotensive placentas. Fetoplacental vascular response to angiotensin II was not affected by preeclampsia or magnesium sulfate. CONCLUSION: In placentas from preeclamptic pregnancies there is increased fetoplacental perfusion pressure, which decreases with exposure to sulfate.     

Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia

OBJECTIVE: To investigate the changes in enzyme activities of erythrocyte superoxide dismutase (SOD), catalase, and placental glutathione peroxidase (GSH-Px), and analyze the levels of serum malondialdehyde (MDA), copper (Cu), zinc (Zn), selenium (Se), leptin and placental MDA and glutathione (GSH). STUDY DESIGN: Cross-sectional prospective study consisting of 32 preeclamptic (PE) pregnant, 25 non-pregnant (NP) women, 28 healthy pregnant (HP) women. Levels of lipid peroxides in serum and placenta, and activities of SOD, catalase in erythrocyte and placental GSH level, placental GSH-Px activity were measured by spectrophotometric methods. Serum levels of Cu, Zn, Se measured by atomic absorption spectrophotometry. Serum levels of leptin was measured by enzyme immunoassay by using the Cayman chemical kit. One-way analysis of variance and post hoc Tukey-HSD test and Pearson correlation test were used for the statistical analyses. RESULTS: Serum levels of MDA, Cu, Leptin were markedly higher (P < 0.001); and serum level of Se was markedly lower (P < 0.001) in PE women compared with HP women and NP women. Also, placental MDA level was higher (P < 0.001) and placental GSH-Px activity was lower in PE women compared with HP women. In preeclamptic women erythrocyte catalase activity was markedly increased (P < 0.001), while erythrocyte SOD activity was markedly decreased (P < 0.001) compared to HP women and NP women. Placental GSH level was decreased compared to HP women (P < 0.001). Serum level of Zn was markedly decreased compared to NP women (P < 0.001) but no significant difference was observed in PE pregnant when compared with HP women (P > 0.05). Placental MDA level in PE women had significant negative correlation with serum Se level (r = -0.353, P < 0.05). A negative correlation was found between erythrocyte catalase activity with birth weight (r = -0.528, P < 0.001). Also, there were a significant negative correlation between serum levels of Cu and Se in the preeclamptic women (r = -0.407, P < 0.05). CONCLUSION: Our data demonstrate that elevation of lipid peroxides together with impaired antioxidant defense mechanisms and status of trace metals and the presence of possible interrelationship and crosstalk between those parameters may be related at least partly to the pathogenesis of preeclampsia. Additionally, lipid peroxides and blood oxidative imbalance could be part of the cytotoxic mechanisms leading to endothelial cell injury.     

N-acetylcysteine restores nitric oxide-mediated effects in the fetoplacental circulation of preeclamptic patients

OBJECTIVE: Preeclampsia is associated with an imbalance between oxidants and antioxidants, resulting in reduced effects of the endothelium-derived, relaxing-factor nitric oxide (NO). Antioxidants, like N-acetylcysteine (NAC), remove reactive oxygen species, resulting in an improvement of endothelial function. We aimed to investigate the effect of NAC on the NO-pathway in the human fetoplacental circulation in preeclampsia and control pregnancies. STUDY DESIGN: The NO-pathway was investigated by use of the NO-synthase inhibitor L-NAME in an ex vivo cotyledon perfusion model. RESULTS: At baseline, fetoplacental arterial pressure was comparable in preeclamptic pregnancies (n=8) and control pregnancies (n=8), and increased dose-dependently after L-NAME. The maximal L-NAME-induced rise in fetoplacental arterial pressure was attenuated in preeclamptic versus control pregnancies (20.8 +/- 2.0 mm Hg vs 36.7 +/- 3.5 mm Hg, P<.05). Addition of NAC increased the L-NAME-induced rise in fetoplacental arterial pressure to 36.4 +/- 3.4 mm Hg in preeclampsia pregnancies (P<.05) and to 49.2 +/- 2.6 mm Hg in control pregnancies (P<.05). CONCLUSION: Preeclampsia is associated with a dysfunction of the NO-pathway. N-acetylcysteine increases NO-mediated effects in the fetoplacental circulation in preeclamptic placentas as well as in healthy control placentas.     

Placental superoxide is increased in pre-eclampsia

One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct method to detect free radicals in tissues, was used to measure superoxide levels in placentae from normal pregnancies (n=13) and pregnancies complicated by PE (n=10). The superoxide level was significantly increased in the placental tissue of pre-eclamptic women. Moreover, upon inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of the superoxide levels was significantly smaller in the placentae from the PE patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct support to the hypothesis that oxidative stress in placental tissue is increased in PE.     

PAF levels and PAF-AH activities in placentas from normal and preeclamptic pregnancies

OBJECTIVE: The aim of this study was to determine: (1) platelet-activating factor (PAF) levels and PAF-acetylhydrolase (PAF-AH) activities in normal and preeclamptic placentas; (2) lipid peroxide production by placental tissues stimulated with PAF. METHODS: Placentas were obtained immediately after delivery from normal and preeclamptic pregnancies. Tissue pieces were snap frozen in liquid nitrogen and stored at -70 degrees C. One gram of tissue from each placenta was used for PAF extraction and for total RNA isolation. PAF was measured by PAF [3H] scintillation proximity assay (SPA) system. Trophoblast PAF-AH activity was determined by enzyme-linked immunosorbent assay (ELISA). mRNA expression for PAF receptor was assessed by RNase protection assay (RPA). Normal placental explants were incubated with PAF at concentrations of 1 and 10 microg/ml for 48 h. Lipid peroxide productions of 8-isoprostane and malondialdehyde (MDA) were measured by ELISA and thiobarbituric acid reaction, respectively. Data were presented as mean+/-SE and analyzed by nonparametric Mann-Whitney U test and ANOVA. A p level less than 0.05 was considered statistically significant. RESULTS: (1) The mean tissue level for PAF was elevated, but not statistically different, in preeclamptic (n=7) than in normal (n=8) placentas, 6.45+/-1.05 versus 4.47+/-0.60 ng/g, p=0.42. (2) PAF-AH activity was higher in trophoblasts from preeclamptic (n=7) placentas than that in trophoblasts from normal (n=8) placentas, 0.69+/-0.16 versus 0.38+/-0.03 micromol/min/microg protein, p<0.05. (3) The relative mRNA expression for PAF receptor was not different between normal (0.70+/-0.08) and preeclamptic (0.76+/-0.13) placental tissues, p=0.60. (4) Productions of 8-isoprostane and MDA were not increased in tissues with PAF in culture, 8-isoprostane: 0.37+/-0.09 ng/mg (control) versus 0.32+/-0.09 ng/mg (1 microg/ml) and 0.37+/-0.07 ng/mg (10 microg/ml), p>0.5; MDA: 0.62+/-0.05 nmol/mg (control) versus 0.68+/-0.04 nmol/mg (1 microg/ml) and 0.69+/-0.03 nmol/mg (10 microg/ml), p>0.5. CONCLUSIONS: Increased PAF-AH activity in trophoblasts may be a compensatory effect to control PAF level in the preeclamptic placenta. The co-existence of PAF-AH and PAF receptor in trophoblasts suggests an autocrine regulation of PAF in these cells to limit PAF and its metabolites within the placenta.     

Increased neutrophil-endothelial adhesion induced by placental factors is mediated by platelet-activating factor in preeclampsia.

OBJECTIVE: Endothelial cell activation or dysfunction and neutrophil-endothelial cell adhesion have been suggested to be important in the pathophysiology of preeclampsia. However, the mechanisms that underlie the alteration of endothelial cell function in preeclampsia are unknown. Placenta from preeclamptic pregnancies produces mediators and autacoids, which may be released into the maternal circulation and modulate endothelial function. In this study, the effect of placental factor(s) on neutrophil-endothelial adhesion and the possible role of platelet-activating factor (PAF) in mediating the response have been examined. METHODS: Endothelial cells were isolated from human umbilical veins (HUVECs) from normal pregnancies. Confluent primary passage HUVECs were exposed to conditioned medium derived from normal and preeclamptic placental tissue cultures, with unconditioned medium as a control. Placental-conditioned medium was prepared by incubation of placental whole villous tissue in Dulbecco's Modified Eagle's Medium (DMEM) for 48 hours. Neutrophil-endothelial adhesion assays were performed to evaluate placental factors in mediating neutrophil-endothelial adhesion, and a PAF-3H scintillation proximity assay (SPA) system was used to determine endothelial PAF production. The PAF-receptor antagonist WEB 2086 was used to block placental factor-mediated increased neutrophil-endothelial adhesion induced by conditioned medium derived from preeclamptic placenta. RESULTS: Neutrophils were significantly more adherent to HUVECs treated with conditioned medium from preeclamptic placentas (28.44 +/- 2.47%) than to HUVECs treated with conditioned medium from normal placentas (18.95 +/- 1.57%) or with unconditioned medium (14.60 +/- 1.29%, P < .01). Also, HUVECs exposed to preeclamptic placental-conditioned medium produced more PAF than the cells exposed to normal conditioned medium and unconditioned medium, 416.18 +/- 17.14 pg/1 x 10(7) cells versus 330.90 +/- 35.70 and 296.43 +/- 44.40 pg/1 x 10(7) cells, P < .05, respectively. The PAF receptor antagonist WEB 2086 completely blocked increased neutrophil-endothelial adhesion induced by preeclamptic placental-conditioned medium (13.24 +/- 0.81% versus 31.31 +/- 4.75%, P < .01). CONCLUSION: In preeclampsia, the placenta releases one or more factors promoting neutrophil-endothelial adhesion. The increased neutrophil-endothelial adhesion thereby induced is a PAF-mediated event. It is suggested that if preeclamptic placentas release toxic factors into the maternal circulation in vivo, these factors may contribute to the altered vascular endothelial cell function in preeclampsia.     

Increased levels of macrophage migration inhibitory factor (MIF) in preeclampsia

OBJECTIVE: MIF is a proinflammatory cytokine involved in reproduction. Systemic activation of maternal inflammatory cell responses may play an important role in the pathogenesis of preeclampsia (PE). We hypothesized that MIF could be involved in preeclampsia. STUDY DESIGN: Concentration of immunoreactive MIF was assayed by enzyme-linked immunoassorbent assay (ELISA) in maternal serum samples obtained from 41 term control pregnancies and 21 severe preeclamptic pregnancies (14 delivered before and 7 at or after 34 weeks). RESULTS: MIF serum levels were significantly higher in preeclamptic pregnancies (median 12.74 ng/ml) than in control group (median 5.3n g/ml) p = 0.001. MIF concentration was significantly higher when delivery occurred <34 weeks (median 17.80 ng/ml; range 2.80-80.20) than in the group delivered > or = 34 weeks (median 6.16 ng/ml; range 1.62-23.65) p = 0.037. CONCLUSIONS: High maternal serum levels MIF in pregnancies complicated by severe preeclampsia strongly support the role of inflammation in the pathogenesis of this disease.     

An image analysis technique for the investigation of variations in placental morphology in pregnancies complicated by preeclampsia with and without intrauterine growth restriction

OBJECTIVE: The purpose of this study was to use visual image analysis to observe changes in the morphology and composition of placental villi in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR). METHODS: Placental biopsies from nine normal pregnancies, five cases of PE, five cases of IUGR, and five cases of PE with IUGR (PE x IUGR) were randomly sampled. Formalin-fixed, wax-embedded sections were stained with hematoxylin and eosin (H&E) and subjected to image analysis. The placental areas occupied by villi, syncytiotrophoblast, and syncytial cytoplasm and nuclei were quantified. RESULTS: Significantly smaller placentas were obtained from growth-restricted pregnancies. PE, with and without IUGR, had no effect on the total area occupied by villi or intervillous space. IUGR alone showed a real and consistent reduction in villous area (56.0 +/- 2.4% vs 43.6 +/- 3.3%, P <.03). While the ratio of syncytial to villous areas were noticeably reduced in all cases of PE (0.38 +/- 0.03 vs 0.24 +/- 0.07, P <.05), this ratio remained unchanging in IUGR. Birth weight was positively correlated to both placental size and total villous area occupied. Moreover, increasingly positive relationships were recorded between both syncytiotrophoblast area and syncytiotrophoblast cytoplasm and birth weight (P <.01 and P <.001, respectively). CONCLUSION: These measurements point to impoverished villus development in idiopathic IUGR. The observed changes in PE with IUGR were more akin to PE without growth restriction than IUGR alone. This suggests that idiopathic IUGR and IUGR in PE have a separate etiology, idiopathic IUGR arising through a reduction in villous area alone, and IUGR in PE caused by changes in syncytiotrophoblast quantity, more specifically the amount of syncytiotrophoblast cytoplasm.     

Bioactivity of serum hCG in preeclampsia

OBJECTIVE: To compare hCG levels, obtained by biologic and immunologic means, in women with normal pregnancies and women with preeclampsia. METHODS: Peripheral blood samples from women in the third trimester with preeclampsia (n = 30) or normal pregnancies (n = 30) were assayed for immunoactive and bioactive hCG (mouse Leydig cell testosterone production assay). RESULTS: Serum bioactive hCG levels tended to be lower than normal, and immunoactive hCG levels tended to be higher in women with preeclampsia, but the differences were not statistically significant. However, the ratio of bioactive to immunoactive hCG was significantly lower than normal for preeclamptic women (0.70 +/- 0.28 vs. 1.15 +/- 0.35 for normotensive pregnant women [mean +/- standard deviation], P <.001). CONCLUSION: The ratio of bioactive to immunoreactive serum hCG is lower among preeclamptic than among normotensive pregnant women.     

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.     

妊娠肝内胆汁淤积症患者血硒及胎盘硒水平变化与胎盘组织学改变的关系

OBJECTIVE: To explore the effect of deficiency of blood selenium and placental selenium on the damage of histomorphology of the placentas in ICP. METHODS: We measured the selenium concentration by a catalytic polorographic method in blood and placenta and glutathione peroxidase (GSH-Px) activity by a 5,5'-dithionbis (2-nitrobenzoic acid) direct method in blood in 30 women with ICP (ICP group) and 30 normal pregnant women (control group). Furthermore, the features of the placentas (10 from control group and 10 from ICP group) pathologic changes were observed microscopically. RESULTS: (1) The selenium concentrations in blood (0.0389 +/- 0.0090) mg/L and placenta (0.3770 +/- 0.0964) mg/kg and the activity of GSH-Px (59.31 +/- 11.42) U in ICP group were found to be significantly lower than those in blood (0.0477 +/- 0.0094) mg/L and placenta (0.4554 +/- 0.0626) mg/kg and the activity of GSH-Px (68.48 +/- 10.47) U in control group, respectively (P < 0.002). (2) The activity of GSH-Px had a significant positive correlation with selenium concentration in blood in ICP group (r = 0.05498, P < 0.001) and in control group (r = 0.06234, P < 0.001). There was a positive correlation between blood and placental selenium concentrations in ICP group (r = 0.6473, P < 0.001). On the other hand, there was not correlation in women with normal pregnancies. (3) Placentas obtained from women with ICP had swelling and fibrinoid necrosis of villi, increasing number of syncytial sprouts, thickening of vasculo-syncytial membrane (VSM) and decreasing size of the intervillous space under light microscopy. Placentas from control group did not show the pathologic changes as mentioned above. CONCLUSIONS: As selenium constitutes the active part of GSH-Px, these results suggest that the placental selenium deficiency may lead to reduced placental GSH-Px activity and the antioxidative defence may have been defective which may be associated with the damage of histomorphology of the placentas in ICP.     

Evaluation of VEGF in placental bed biopsies from preeclamptic women by immunohistochemistry

OBJECTIVE: The aim of the study was to determine VEGF protein with immunohistochemical staining in placental bed biopsies of preeclamptic pregnancies in comparison to normal controls. DESIGN: Prospective cohort study. METHODS: The placental bed biopsies were obtained from 12 patients with preeclapmsia and ten patients for a control group at the time of cesarean delivery. Tissue samples of the placental bed were examined for VEGF protein distribution with avidin-biotin-peroxidase immunohistochemistry. Two blinded histopathologists were asked to score each sample for the intensity of staining and the number of cells stained in a randomly selected HPF of each sample. The resulting "H-score" was computed as a product of intensity and percent of cells stained. RESULTS: VEGF expression was significantly lower in both the myometrium and stroma of the preeclamptic group compared to the control group (77.2 +/- 25.4 vs 134 +/- 44.3, p = 0.007; 194.1 +/- 20.7 vs 170.2 +/- 17, p = 0.017, respectively). CONCLUSION: VEGF expression is significantly lower in placental bed biopsies of preeclamptic pregnancies.     

重度子(癎)前期和正常妊娠胎盘中微小RNA-155及富含半胱氨酸蛋白61的差异表达

目的 探讨微小RNA-155(microRNA-155,miR-155)和富含半胱氨酸蛋白61(cysteine-rich 61,CYR61)在重度子(癎)前期和正常妊娠胎盘中差异表达的意义. 方法取18例重度子(癎)前期患者(孕36～40周)胎盘和同期分娩且孕周匹配的18例正常产妇胎盘,从mRNA水平检测miR-155和CYR61 mRNA的表达情况,并在蛋白水平检测CYR61的表达情况. 结果 与正常产妇胎盘相比,重度子(癎)前期组胎盘的miR-155表达水平明显增高(165.7±16.4和527.9±49.1,t=7.00,P＜0.01);而CYR61 mRNA表达水平及蛋白表达水平均降低(31.7±2.7和16.4±1.2,t=5.10,P＜0.01;36.4±1.5和19.7±1.2,t=36.26,P＜0.01).重度子(癎)前期和正常妊娠胎盘组织中的miR-155与CYR61 mRNA的检测结果的相关性分析显示,两组内两者表达均呈负相关(r=-0.52,P＜0.05;r=-0.57,P＜0.05). 结论重度子(癎)前期患者胎盘中miR-155的上调,可能与促血管生成因子-CYR61的表达下降有关.miR-155、CYR61可能共同参与了子(癎)前期胎盘血管缺陷的发生.     

Reduced amount of cytochrome c oxidase subunit I messenger RNA in placentas from pregnancies complicated by preeclampsia

BACKGROUND: Cytochrome c oxidase is a marker enzyme of the mitochondrial inner membrane. A change in the structure and activity of cytochrome c oxidase may alter the electron transport in the inner membrane, leading to insufficient adenosine triphosphate (ATP) production. ATP is essential for maintaining the function of cells. The aim of this study was to compare the expression of cytochrome c oxidase subunit I mRNA in placentas from normal and preeclamptic pregnancies. METHODS: By means of in situ hybridization, frozen sections of placentas from 23 women with preeclampsia and 29 women with uneventful pregnancies were examined. Digoxigenin (DIG)-labeled probes were used to detect the expression of cytochrome c oxidase subunit I mRNA in the placentas. The expression density was assessed by using an image disposal and analysis system. RESULTS: Positive expression of cytochrome c oxidase subunit I mRNA was found in the cytoplasm of villous syncytiotrophoblasts. The mean light density of cytochrome c oxidase subunit I mRNA in placental villi of normal pregnant women was 0.2638, and 0.1763 in women with preeclampsia, a statistically significant difference (P < 0.05). The number density of cytochrome c oxidase subunit I mRNA in placental villi was also significantly reduced in preeclamptic women compared with the control group (P < 0.05). CONCLUSIONS: Our study demonstrates a reduced amount of cytochrome c oxidase subunit I mRNA in preeclamptic placentas compared to control placentas. We hypothesize that a reduced expression may play a role in the pathophysiology of preeclampsia.