Expression of Human Leukocyte Antigen-G during Normal Placentation and in Preeclamptic Pregnancies

Objectives. This study was undertaken to investigate the expression pattern of human leukocyte antigen-G (HLA-G) during normal placentation and determine whether altered expression of HLA-G is associated with severe preeclampsia. Methods. We investigated HLA-G protein levels in first (n = 27), second (n = 7), and third trimester placentas (n = 10) from normal pregnancies, and determined HLA-G levels in term placentas from normal (n = 15) and severe preeclamptic pregnancies (n = 14) using real-time RT-PCR and western blot analysis. Results. In normal placentas, HLA-G protein expression reached a peak level at gestational weeks 6 and 7, then gradually decreased from week 8 to third trimester (p < 0.05). In preeclamptic placentas, both HLA-G mRNA and protein levels were decreased significantly in comparison with normal term placentas (p < 0.05). Conclusion. HLA-G may contribute to placentation during early and mid-term pregnancy, and participate in maintaining gestation during term pregnancy. The reduced level of HLA-G may be associated with pathogenesis of preeclampsia.     

Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in the placenta of pregnancies complicated with preeclampsia

Abstract

Background: Preeclampsia has been related to single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate reductase (MTHFR) gene; however, data regarding the placenta are still lacking.

Objective: To determine the frequency of C677T and A1298C SNPs of the MTHFR gene in the placenta of preeclamptic pregnancies and healthy controls.

Methods: Genotyping of C677T and A1298C polymorphisms of the MTHFR gene using RFLP-PCR was performed to the placenta of 100 gestations (n?=?50 complicated with preeclampsia and n?=?50 normal controls matched for parity and maternal age).

Results: Gestational age at birth and neonatal and placental weight were significantly lower in women with preeclampsia as compared to controls. The TT genotype of the C677T polymorphism was threefold more prevalent in preeclamptic placentas as compared to the placenta of controls (24.0% versus 8.0%, p?=?0.001). Upon pooled analysis (n?=?100), placental and neonatal weights were significantly lower in placentas displaying this genotype (TT, C677T) as compared with the CC genotype.

Conclusion: This study found that the frequency of the TT mutant genotype of the C677T polymorphism was higher in the placenta of pregnancies complicated with preeclampsia. There is a need for further research in this matter.     

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.     

Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women

Objective: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preeclampsia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preeclamptic women.

Methods: One hundred seventy-five nulliparous Sinhalese women with preeclampsia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preeclampsia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system.

Results: The prevalence of the CT genotype of IL1A rs17561 polymorphism was increased in preeclamptic women compared with controls {p?=?0.04, odds ratio (OR) [95% class interval (CI)]?=?1.6 (1.0–2.5)}. The prevalence of the CT genotype [p?=?0.01, OR (95% CI)?=?1.8 (1.1–2.8)] and the dominant model (CT?+?TT) [p?=?0.03, OR (95% CI)?=?1.6 (1.1–2.5)] of the IL1A rs1800587 polymorphism were increased in preeclamptic women compared with controls. The prevalence of the GA genotype [p?=?0.04, OR (95% CI)?=?0.6 (0.4–0.9)] and the dominant model (GA?+?AA) [p?=?0.03, OR (95% CI)?=?0.6 (0.4–0.9)] of the MBL1 rs1800450 polymorphism were reduced in preeclamptic women compared to controls.

Conclusion: Genotypes conferring a pro-inflammatory phenotype are increased in preeclamptic women.     

Expression levels of cyclooxygenase-2, tumor necrosis factor-α and inducible NO synthase in placental tissue of normal and preeclamptic pregnancies

Objective: Although preeclampsia (PE) is one of the most important problems affecting pregnant women, etiologic factors in its development are still unclear. We aimed to investigate the expression levels of cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and inducible NO synthase (iNOS) in preeclamptic and healthy control placentas. Patients and methods: Placental tissue samples were obtained after delivery from patients diagnosed with PE and from normal-term pregnants and analyzed for COX-2, TNF-α and iNOS expression by immunohistochemistry. Results: A strong expression of COX-2 was observed in syncytiotrophoblast cells of preeclamptic placentas, which was significantly higher than that of normal placentas (p?=?0.005). A mild expression of TNF-α in both normal and preeclamptic syncytiotrophoblasts was seen (p?=?0.435). In addition, a strong expression of iNOS in normal syncytiotrophoblasts was found, but the intensity of the iNOS expression was highly reduced in preeclamptic placentas (p?=?0.001). No correlation was detected between COX-2, TNF-α and iNOS expression levels. Conclusion: The findings of a decrease of iNOS expression and an increase of COX-2 expression in placenta suggest the existence of functional roles of iNOS and COX-2 in the pathophysiology of PE, probably by contributing to the reduced placental blood flow and increased resistance to flow in the fetomaternal circulation.     

SLC41A1 is the only magnesium responsive gene significantly overexpressed in placentas of preeclamptic women

Objective: To examine expression profile of magnesium responsive genes (MRGs) in placentas of normoevolutive and preeclamptic women. Methods: The expression profiles of MRGs were determined in placentas of normoevolutive (N?=?26) and preeclamptic (N?=?25) women by RT-qPCR. Results: Among all tested MRGs (9) only SLC41A1 (encoding for Na⁺/Mg²⁺ exchanger) was significantly overexpressed in ～54.2% of preeclamptic (n?=?24) and in ～9.5% of normoevolutive (n?=?21) specimens. On average, SLC41A1 was overexpressed sixfold in the preeclamptic group. Presence of SLC41A1 in placentas was confirmed by Western blot analysis. Conclusion. SLC41A1 is significantly overexpressed in nearly 55% of preeclamptic placentas. This may indicate a direct contribution of changed Mg homeostasis in the development of preeclampsia.     

Placental pathology in smoking and non-smoking preeclamptic women

Objective: To ascertain whether the protective effect of smoking during preeclampsia (PE) can be visualized in the placenta.

Methods: The study cohort consisted of placentas (n?=?523) from pregnancies complicated by PE, delivered at Karolinska University Hospital in Stockholm during the period 2000–2009. Of the women included in the study, 488 were non-smokers and 35 were smokers at first visit to maternity care. Outcome variables were placental infarctions and decidual arteriopathy.

Results: Infarctions (affecting ≥5% of the placental tissue) were found in 15.6% of the placentas from non-smokers and in 25.7% of the placentas from smokers (OR 1.88: CI 0.84–4.16, p?=?0.12). Decidual arteriopathy was found in 27.5% of the placentas from non-smokers and in 40.0% of the placentas from smokers (1.76: CI 0.87–3.56, p?=?0.12). When diagnosed histopathologically, placental abruption was found in 15.4% among non-smokers and in 17.1% among smokers (1.14: CI 0.46–2.84, p?=?0.98). Those differences did not show any statistical significance.

Conclusion: No significant differences concerning placental infarctions, decidual arteriopathy or abruption were found between preeclamptic placentas from non-smokers compared to smokers.     

The assessment of placental volume and mean gray value in preeclamptic placentas by using three-dimensional ultrasonography

Objectives: We aimed to evaluate the placental volume and placental mean gray value in preeclampsia and healthy placentas by using three-dimensional (3D) ultrasonography and Virtual Organ Computer-aided AnaLysis (VOCAL).

Methods: This case–control prospective study consisted of 27 singleton pregnancies complicated by preeclampsia and 54 healthy singleton pregnancies matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. The placental volume (cm³) was analyzed using the VOCAL imaging program, and 3D histogram was used to calculate the volumetric mean gray value (%).

Results: Preeclamptic and control group consisted of 27 (mean age: 28.90?±?5.95 years, mean gestation: 32.0?±?4.55 weeks) and 54 (mean age: 29.48?±?5.78 years, mean gestation: 32.61?±?4.23 weeks) singleton pregnancies, respectively. Placental volume was significantly smaller in preeclampsia (250.62?±?91.69 versus 370.98?±?167.82?cm³; p?=?0.001). Volumetric mean gray value of the placenta was significantly higher in preeclampsia (38.24?±?8.41 versus 33.50?±?8.90%; p?=?0.043). Placental volume was significantly correlated with the estimated fetal weight (r?=?0.319; p?=?0.003). There was negative significant relation between placental volume and umbilical artery pulsatility index, resistance index and systolic/diastolic ratio (r?=?–0.244, p?=?0.024; r?=?–0.283, p?=?0.005; r?=?–0.241, p?=?0.024, respectively).

Conclusions: Placental volume diminishes significantly in preeclampsia, whereas volumetric mean gray values increases. This may reflect the early alterations in preeclamptic placentas, which may help to understand the pathophysiology better.     

Maternal serum glycodelin levels in preeclampsia and its relationship with the severity of the disease

Purpose: Preeclampsia, in which insufficient trophoblastic invasion is thought to be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin is a regulator of immunosuppression, fertilization, implantation, and placentation. Because of its inhibitory effects on trophoblastic activity, trophoblast invasion is disturbed when its levels alter. We aimed to analyze serum glycodelin levels in preeclampsia and evaluate whether it correlates with the severity of disease.

Methods: This is a prospective case–control study conducted in a research and training hospital between March and September 2016. In this study, a total of 55 preeclamptic and 65 healthy pregnants were included. Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild. Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent assay.

Results: Glycodelin levels were higher in preeclamptic group as compared with controls (71.38?±?22.78 versus 42.32?±?12.28?ng/ml, p?p?r?=?0.637 and r?=?0.714, respectively, p?r?=?0.369, p?=?.006 and r?=?0.377, p?=?.005) and proteinuria (r?=?0.342, p?=?.011). Moreover, it was correlated with birth weights and gestational age at delivery (r?=??0.386, p?=?.004 and r?=??0.394, p?=?.003, respectively). The role of glycodelin to diagnose preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under the curve for glycodelin is 0.897 with p?53.64?ng/ml. Moreover, area under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p?83.97?ng/ml.

Conclusion: Glycodelin may be a promising marker in predicting the presence and severity of preeclampsia.     

Neuronal apoptosis in the neonates born to preeclamptic mothers

Abstract

Objective: Preeclampsia may result in uteroplacental insufficiency and chronic intrauterine fetal distress. The aim of this study is to address this issue investigating neuronal apoptosis in an experimental model of preeclampsia and to evaluate the neurological outcome of the perinatal asphyxia in the neonates born to preeclamptic mother.

Materials and methods: Two out of four pregnant Sprague–Dawley rats (preeclamptic group) were given water containing 1.8% NaCl on gestation day 15 and 22 in order to establish the model of preeclampsia whereas other two (non-preeclamptic group) received normal diet. A model of perinatal asphyxia was established on the postnatal 7th day to one preeclamptic and one non-preeclamptic dam. Overall 23 pups born to overall four dams were decapitated to assess neuronal apoptosis by the TUNEL assay.

Results: The number of apoptotic neuronal cells was significantly higher in the preeclampsia groups in comparison with the control group (p?=?0.006 and p?=?0.006, respectively). It was also significantly higher in the asphyctic/non-preeclamptic group than the count in the control group (p?=?0.01). There was also significant difference between both asphyctic groups (p?=?0.003).

Conclusion: We conclude that preeclampsia causes small babies for the gestational age and cerebral hypoplasia. Both preeclampsia and perinatal asphyxia can cause increased neuronal apoptosis in the neonatal brains. However, the prognosis for neurological outcome is much worse when the perinatal asphyxia occurs in newborns born to preeclamptic mothers.     

P-wave and QT dispersion in hypertensive disorders of pregnancy

Abstract

Aim: To compare P-wave and QT dispersion values in hypertensive disorders of pregnancy and controls and also in preeclampsia, chronic hypertension, and gestational hypertension separately.

Material and methods: We included 140 hypertensive pregnants and 110 healthy age-matched pregnants in this study. The hypertensive pregnants were divided into three subgroups: preeclampsia (n?=?43), chronic hypertension (n?=?51), and gestational hypertension (n?=?46). P-wave and QT dispersion values were compared between groups.

Results: Hypertensive pregnants had higher P-wave (41.74?±?5.51 vs. 37.73?±?5.62, p?<?.001) and QTc dispersion (45.44?±?7.62 vs. 39.77?±?8.34, p?<?.001) values. In subgroup analysis, P-wave dispersion and QTc dispersion were different between preeclamptic, chronic hypertensive, and gestational hypertensive patients. Also, they were significantly higher in chronic hypertension as compared to gestational hypertension and they were higher in preeclampsia than in gestational hypertension. No difference was found according to these parameters between preeclampsia and chronic hypertension. In correlation analysis, both P-wave dispersion and QTc dispersion were positively correlated with systolic (r?=?0.409, p?<?.001 and r?=?0.306, p?<?.001) and diastolic blood pressure (r?=?0.390, p?<?.001 and r?=?0.287, p?<?.001) which are main clinical determinants of hypertensive disorders.

Conclusion: In clinical practice, chronic hypertensive pregnants are generally followed up in their future life for cardiovascular disorders. Also, we recommend that we must inform and follow preeclamptic patients for future cardiovascular diseases.     

Increased Placental Telomerase mRNA in Hypertensive Disorders of Pregnancy

Objective.?We assessed hTERT mRNA levels in normal versus preeclamptic placental samples, examining hTERT expression levels in different clinical manifestations of hypertensive disorder of pregnancy.?Methods.?We performed a single-site, prospective case-control study of hTERT mRNA levels in placentas from term and preterm pregnancies with hypertensive disorders compared with unaffected pregnancies. Placental biopsies were collected from 61 patients (preeclamptic: 32; non-preeclamptic (control): 29). Total RNA from placenta was isolated and reversely transcribed to c‐DNA. A probe-specific real-time quantitative PCR assay was employed to determine the relative expressional levels of hTERT mRNA levels in these placentas from both unaffected and affected pregnancies with different categories of hypertensive disorders including preeclampsia, severe preeclampsia, eclampsia and HELLP syndrome (Hemolysis, Elevated Liver function tests, Low Platelet).?Results.?The average ratio of hTERT mRNA levels was 1.73 in the preeclamptic group and 1.02 for control group (p < 0.0001). The hTERT expression levels were elevated for each of the different categories of hypertensive disorders of pregnancy compared with control: HELLP syndrome 1.86, severe preeclampsia 1.81, eclampsia 1.71 and mild preeclampsia 1.63. In addition, hTERT levels were higher in severe than mild preeclampsia (p < 0.01). Conclusions.?Elevated hTERT mRNA expression is observed in placentas from pregnancies with different clinical manifestations of hypertensive disorders of pregnancy. The patho-physiological significance of this finding awaits further studies.     

Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO25% inhalation in preeclamptic women

Abstract

Objective: To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2_5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia.

Study design: A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2_5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded.

Results: Baseline PI and RI were lower in the preeclamptic group (p?<?0.05). Inhalation of CO2_5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006?±?0.229 versus 0.503?±?0.209, p?=?0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583?±?0.193 versus 0.383?±?0.173, p?=?0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve?=?0.973, p?=?0.0001).

Conclusion: CVR in response to CO2_5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.     

Post-partum evaluation of maternal cardiac function after severe preeclampsia

Abstract

Objective: To evaluate the post-partum maternal cardiac function in patients with history of severe preeclampsia.

Methods: A series of women with previous singleton pregnancy complicated by severe preeclampsia underwent transthoracic echocardiography at 6–12 months from delivery. A group of women with previous uncomplicated pregnancy was selected as controls.

Results: Sixteen women with history of severe preeclampsia were enrolled in the study group whereas 18 patients were selected as controls. In the study group systolic (p?=?0.002) and diastolic blood pressure (p?=?0.044) were significantly higher. Significant differences were observed in systolic left ventricular (LV) parameters, such as cardiac output (p?=?0.034), LV mass indexed to BSA (p?=?0.024) and longitudinal contraction, expressed by tissue Doppler (TD) S₁ wave, which resulted relatively impaired in former preeclamptic women (p?=?0.049). As regards as diastolic parameters, pulsed Doppler A-wave velocity was increased (p?=?0.036). TD E-wave velocity was significantly lower in study group (p?<?0.001) and E/E₁ ratio (E?=?peak early diastole transmitral wave velocity/E₁?=?peak early diastolic velocity at mitral valve annulus at TD) was higher respect to controls (p?<?0.001).

Conclusions: LV contractility and diastolic function, although within normal reference ranges, show slight but significant impairment among women who experienced a severe preeclampsia. TD seems to be a sensible tool to identify these precocious signs of potential LV dysfunction.     

Expression of inflammatory cytokines in placentas from pregnancies complicated with preeclampsia and HELLP syndrome

Abstract

Objective: To investigate the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in villous trophoblast, syncytial knots and decidua placentas from pregnancies complicated with preeclampsia (PE), Hemolysis, Elevated Liver enzymes and Low Platelet count (HELLP) syndrome and gestational age-matched controls.

Methods: Study group included 35 placentas from pregnancies complicated with PE and 35 placentas from pregnancies with HELLP syndrome. Control group included 35 placentas from idiopathic preterm labor. Placentas were matched according to the gestational age. Expression of TNF-α, IL-6 and IL-10 was determined by immunohistochemistry and semi-quantitative HSCORE method in villous trophoblast, syncytial knots and decidua. Non-parametric statistics were used for analyses.

Results: There was no difference in the expression of TNF-α, IL-6 and IL-10 in all the studied placental segments between PE, HELLP and gestational age-matched control group. TNF-α (F?=?32, 41, p?<?0.001), IL-6 (F?=?58, 53, p?<?0.001) and IL-10 (F?=?17, 62, p?<?0.001) expression was significantly different in different placental cell types, the highest expression of cytokines was in decidua.

Conclusion: There was no difference in cytokine expression in villous trophoblast, syncytial knots and decidua among the studied placental groups. The expression of cytokines was highest in decidua in all the studied placental groups.     

May ratio of neutrophil to lymphocyte be useful in predicting the risk of developing preeclampsia? A pilot study

Objective: The aim of the study was to evaluate the relationship between neutrophil to lymphocyte ratio (NLR) and preeclampsia.

Methods: Demographic data and laboratory tests for NLR of 203 pregnant women (73 normotensive pregnants, 23 pregnants with mild preeclampsia and 107 pregnants with severe preeclampsia) were retrospectively analyzed. Neutrophil to lymphocyte ratios were compared between the study groups.

Results: Preeclamptic pregnant women had smaller gestation weeks, lower hemoglobin level and fetal birth weight than that of normal pregnant women. NLR in preeclamptic group was significantly higher than that of normal group (p?=?0.023) and area under ROC curve was found statistically significant (p?=?0.023). However, there was no statistically significant relationship between NLR and severity, proteinuria level, subjective symptoms and onset time of the disease.

Conclusion: The findings showed that the measurement of NLR periodically may be useful to predict high-risk pregnancies in terms of preeclampsia, but further studies are needed to determine its contribution.     

Preeclampsia is associated with an elevation of plasma sMet concentrations in the second trimester

Abstract

Objective: The aim of this study was to investigate the association between anti-angiogenic factor soluble c-Met (sMet) concentrations in maternal plasma and the risk of preeclampsia.

Methods: The pregnant women included in this study (1) had subsequent preeclampsia (n?=?52) and were compared to normal controls (n?=?104) at the time of amniocentesis (15–20 weeks); and (2) had preeclampsia (n?=?63) and were compared to normal controls (n?=?112) at the time of diagnosis of preeclampsia (29–40 weeks). sMet concentrations were measured by ELISA. Non-parametric statistics were used for analysis.

Results: Maternal plasma sMet concentrations were significantly higher in both women with subsequent preeclampsia (median: 1372.7?ng/ml versus 1100.5?ng/ml; p?=?0.036) and women with preeclampsia (median: 1651.9?ng/ml versus 1364.7?ng/ml; p?<?0.001) than in the controls. After adjusting for potential confounding factors, the risks of developing preeclampsia were as follows: adjusted odds ratio 2.5 (95% confidence interval, 1.2–5.2; p?=?0.016) for second trimester sMet concentration with a cut-off value of 1223.5?ng/ml and 4.4 (95% confidence interval, 2.2–9.1; p?<?0.001) for third trimester sMet concentration with a cut-off value of 1460.3?ng/ml.

Conclusion: Elevated maternal plasma sMet concentrations were independently associated with the increased risk of preeclampsia.     

Newborn LpL (Ser447Stop,Asn291Ser) genotypes and the interaction with maternal genotypes influence the risk for different types of preeclampsia: modulating effect on lipid profile and pregnancy outcome

Aim: To establish that newborn Ser447Stop and Asn291Ser may have interactive effects with maternal genotypes on the plasma lipoprotein levels, risk of preeclampsia as well as on the prognosis of preeclampsia.

Materials and methods: Seventy preeclamptic women and 94 normotensive pregnant women, and their newborns were genotyped using PCR-RFLP methods.

Results: The risk of mild and severe preeclampsia was 4 (p?=?0.004) and 5.18 (p?=?0.001), respectively, if both the mother and newborn were carriers of the Ser447/Ser477 genotype. If both the mother and newborn were carriers of the Asn291Ser variant, the risk to develop severe preeclampsia was 6.07 (p?=?0.03). Women with mild and severe preeclampsia had higher TG (p?p?p?=?0.008; p?Ser447/Ser447 genotype. Women with severe preeclampsia had significantly higher TG (p?=?0.03) and LDL-C levels (p?=?0.037) if both the mother and newborn were carriers of Asn291Ser. Newborn/maternal LpL interaction had no statistically significant influence on pregnancy outcome.

Conclusions: The newborn/maternal LpL interaction influences the severity of preeclampsia and modulates the lipid profile particularly in severe preeclampsia.     

Promoter hypomethylation and increased maspin expression in preeclamptic placentas in a Chinese population

ObjectivePreeclampsia is thought to begin with shallow trophoblast invasion and inadequate spiral artery remodeling. Maspin, a tumor-suppressor gene, plays a regulatory role in trophoblast invasion and motility. The tissue-specific methylation of the maspin promoter can regulate maspin gene expression in various cancers. We sought to detect maspin gene expression and assess the degrees of methylation of maspin promoter regions in preeclamptic placentas in the Han Chinese population and to investigate the potential role of maspin in the pathophysiology of preeclampsia.MethodsWe conducted RT-PCR, immunohistochemistry and western blotting to characterize maspin gene expression and protein levels in the placentas from normal and preeclamptic pregnancies. Finally, using methylation-specific PCR and bisulfite sequencing PCR, we detected the degrees of methylation of the promoter regions of maspin in each of the two studied groups.ResultsMaspin expression was increased at the mRNA and protein levels in the preeclamptic placentas compared to the control group. Maspin immunohistochemical staining revealed positive staining in the syncytio-cytotrophoblast layers and more diffuse staining in the preeclamptic group. The mean methylation level of the analyzed promoter region was significantly hypomethylated in the preeclamptic placentas compared to the control placentas, pointing to a negative relationship between maspin promoter methylation and gene expression.DiscussionHypomethylation of the maspin promoter results in increased expression of maspin in preeclamptic placentas, which suggests a negative relationship between maspin methylation and maspin expression in this Han Chinese population. Thus, maspin is likely involved in the etiology of preeclampsia.