PE Women Research Articles

The influence of Nrf2 gene promoter methylation on gene expression and oxidative stress parameters in preeclampsia

Background and aimsPreeclampsia (PE) is a serious medical condition that usually causes high blood pressure and affects multiple organs. Considering the adverse effect of oxidative stress on the process of PE in pregnant women and regarding the role of the Nrf2 gene in placental oxidative pathways, this study was conducted to investigate the DNA methylation status of Nrf2 in PE and healthy pregnant women.Materials and methodsThe present case-control study consisted of 70 PE and 70 healthy pregnant women. Blood and placenta samples were taken from all subjects, and the percentage of the Nrf2 gene methylation in the samples was assessed by the Methyl Light PCR method. Also, the Nrf2 gene expression was evaluated by real-time PCR. The total antioxidant capacity (TAC) and total oxidative status (TOS) were measured by the colorimetric method.ResultsIn PE women, there was a significant increase in blood pressure, term of pregnancy, and BMI. In addition, there were enhanced Nrf2 DNA methylation percentage in placenta tissue and increased TOS levels in placenta tissue and blood compared to healthy pregnant women (P < 0.05). Also, in the PE group, there was a significant decrease in Nrf2 gene expression and TAC level in placenta tissue compared to the control group (P < 0.05).ConclusionThe Nrf2 gene undergoes epigenetic modifications of DNA hypermethylation in the PE placenta. Decreased expression of this gene and the changes in the level of oxidative parameters (TAC, TOS) confirm it.

Association of ACE*(Insertion/Deletion) Variant with the Elevated Risk of Preeclampsia Among Gestational Women.

The renin-angiotensin-aldosterone system has an indispensable function in the uteroplacental circulation, placental growth, and blood pressure optimization. The angiotensin I converting enzyme (ACE) gene is a critical integrator for electrolyte balance, and water retention, along with inhibiting preeclampsia. The main goal of this pertaining study is to assess the contribution of ACE*(Ins/Del) variant with the susceptibility for preeclampsia with focus on the severity of the disease among gestational hypertensive women. This retrospective study included 225 participants [125 PE gestational women, and 100 normotensive healthy controls] matching with age, and geographical region. PE women classified into 82 early-onset PE women, accompanied with 43 late-onset PE women. Additionally, PE women categorized into 59 mild PE women, together with 66 severe PE women. The genotyping and characterization of ACE*(Ins/Del) variant were applied using the PCR technique. Our findings indicated higher frequency of the ACE*(Del/Del) genotype and ACE*(D allele) with elevated risk of preeclampsia compared to normotensive controls under recessive (OR = 2.09, and p-value = 0.007), and allelic (OR = 1.75, and p-value = 0.012) models. In addition, testing logistic regression revealed that the levels of endothelin-1 and malondialdehyde exposed significant difference for the ACE*(Del/Del) genotype among early-onset and late-onset PE women (p-value = 0.024, and 0.23, respectively). Furthermore, carriers of the ACE*(Del/Del) genotype observed statistically significant with lower sodium concentrations among severe PE women (p-value = 0.034). The ACE*(Del/Del) genotype and ACE*(D allele) were associated with increased risk preeclampsia among gestational women. Furthermore, early-onset PE and late-onset PE were correlated with endothelin-1 and malondialdehyde concentrations among Egyptian women.

Maternal Cardiac Functional and Structural Changes in Preeclampsia: an Echocardiographic Study

Background &amp; objective: Preeclampsia is a pregnancy-induced multi-organ syndrome of acute cardiovascular manifestations with significant short and long-term sequelae. However, there is a relative lack of knowledge with respect to cardiac functional and structural changes in women with preeclampsia Therapeutic interventions used in the management of preeclampsia may cause iatrogenic adverse consequences due to this lack of knowledge. The present study was therefore designed to evaluate the echocardiographic changes in cardiac structural and functional indices in pregnant women with PE. Methods: This cross-sectional study was carried out in the Department of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka Medical College Hospital (DMCH), and Shaheed Suhrawardy Medical College Hospital (SSMCH) in collaboration with National Institute of Cardiovascular Diseases (NICVD), Dhaka over a period of one year from July 2013 to June 2014. A total of 30 single-tone pregnant women of 20-40 weeks gestation with preeclampsia were taken as cases. An equal number of gestationally-matched healthy pregnant (HP) women of similar age cohorts having no history of preexisting hypertension were included as controls. Preeclampsia was defined as SBP ≥140and/or DBP ≥ 90 mmHg after 20 weeks gestation in a woman with previously normal blood pressure and with proteinuria≥1 + in the dipstick test. Pregnant women with systolic and diastolic blood pressures within the normal range (&lt; 140mmHg and &gt; 90 mmHg respectively), trace or absence of proteinuria by dipstick test were defined as controls. All thesubjects were investigated with ECG, standard two-dimensional, M-mode, and Doppler transthoracic echocardiography. The cardiac functional and structural changes were measured in terms of interventricular septal thickness (IVSTd),posterior wall thickness (PWTd), left ventricular internal diameter at the end of diastole (LVIDd), ejection fraction (EF), transmitral velocity (MV E/A ratio), MV deceleration time (MV DecT). Result: Half of the women with preeclampsia were primigravidae and there was no association between gravidity and the occurrence of preeclampsia. Prepregnancy overweight or obesity (in terms of BMI) was found to be strongly associated with preeclampsia. One in 10 PE women had a previous history of preeclampsia as opposed to none in the HP women. A substantial proportion (56.7%) of PE women had a family history of hypertension in comparison to healthy pregnant women (16.3%). The women with PE had significantly higher SBP, DBP, &amp; MAP than the HP women. Parameters of diastolic dysfunction, like mitral E/A ratio was reduced and deceleration time was prolonged in PE with diastolic dysfunction (mean E/A ratio &lt; 0.73 and mean DceT &gt;178 ms respectively) than those in PE with normal diastolic function (mean E/A ratio 1.2 and mean DceT 192.4 ms respectively) healthy pregnant women (mean E/A ratio 1.3 and mean DecT 186.5 ms respectively). Over one-third (36.7%) of women with PE met the criteria of diastolic dysfunction compared to none in healthy pregnant women. The LVH appears to be a frequent occurrence in pregnancies complicated by preeclampsia (43.3%) as compared to none in healthy pregnant women. In the present study, the systolic function was assessed with the help of EF, which was well-preserved both in PE and HP with no significant intergroup difference. Conclusion: Preeclampsia is associated with left ventricular diastolic dysfunction and hypertrophy preserving the systolic function. These structural and functional changes are primarily adaptive in nature for maintaining cardiac systolic function. Ibrahim Card Med J 2022; 12 (2): 32-39

Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study.This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion.Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group.Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

Observation of increased levels of autophagy-related genes and proteins in women with preeclampsia: a clinical study.

Preeclampsia is a type of pregnancy-related disease that is not fully understood underlying mechanisms of it till now. Reported results from autophagy-related studies in PE show some controversial roles of this mechanism in PE development and progression. In this study, we aimed to evaluate the autophagy process in preeclampsia women. Peripheral blood was taken from 50 preeclampsia women and 50 healthy pregnant women. After PBMC isolation, Total RNA and total protein were extracted from PBMCs to cDNA synthesis and real-time PCR and western blotting, respectively. Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes were evaluated using real-time PCR. Atg5, beclin1, LC3B, and FOXO1 expression at the protein level was evaluated by the western blot technique. Real-time PCR results showed an increased expression of Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes in PE patients compared to the healthy pregnant women and also in LOPE patients in comparison with EOPE cases. Western blotting results revealed higher expression of Atg5, beclin1, LC3B, and FOXO1 proteins in PE women compared to healthy pregnant group and in LOPE patients in comparison with EOPE cases. Our findings revealed a positive correlation between proteinuria and protein levels of Atg5, beclin1, LC3B, and FOXO1 in LOPE patients. Our investigation showed an elevated activation of autophagy in PE women in comparison with healthy pregnant women which is in controversy with some other studies. More targeted and comprehensive studies regarding the relationship of autophagy in pre-eclamptic women are needed.

Alterations in the metabolic status of amino acids in newborns of pre-eclampsia women.

Changes in amino acid (AA) levels have been observed in women with pre-eclampsia, but data on their newborns are scarce. This study aimed to evaluate 11 AAs in newborns of 378 PE and 18,666 non-PE pregnant women. We found that the levels of alanine, arginine, glycine, methionine, phenylalanine, valine, and leucine/isoleucine/hydroxyproline in newborns of PE women were significantly higher than those of non-PE women, whereas the level of tyrosine was lower. This different metabolic status deserves further study to determine whether this pattern persists or is likely to increase the risk of future diseases in these newborns.

Effects of pre-eclampsia on HDL-mediated cholesterol efflux capacity after pregnancy

Background and aimsPreeclampsia (PE) is associated with life-long increased risk of cardiovascular disease. One of the main protective functions of high-density lipoprotein (HDL) is its role in reverse cholesterol transport. HDL-mediated cholesterol efflux capacity (CEC) is decreased during pregnancy in women with PE. Whether this persists postpartum is unknown. MethodsBasal and transporter-specific CEC were determined 6 months postpartum in women who had a normotensive (n = 44) or a PE (n = 42) pregnancy. CEC was also measured in 23 normotensive and 20 PE women for whom samples were collected 24 months postpartum. Basal, ATP-binding cassette transporter-A1 (ABCA1)- and -G1 (ABCG1)-specific CEC were primarily determined using Chinese hamster ovary cells stably expressing human ABCA1 or ABCG1, and were also assessed using a J774 mouse macrophage cell line. ResultsABCA1-specific CEC was significantly lower in women who had PE 6 months postpartum (0.57 ± 0.1 vs 0.53 ± 0.08; p < 0.05), whilst basal and ABCG1-specific efflux were not significantly different. cAMP-specific CEC in J774 cells was also lower 6 months after PE (0.85 ± 0.21 vs 0.75 ± 0.25, p < 0.05). Although apoA-I, apoE, plasminogen and PON-1 levels were not significantly different in women who had PE compared with controls, ABCA1 efflux did correlate with apoA-l, HDL-C and apoE levels after a normal, and with apoA-l and HDL-C levels after a PE pregnancy. ABCA1-specific efflux decreased in all women between 6 and 24 months postpartum, by 11 ± 1.6% in women who had a normotensive pregnancy and 9 ± 1.3% in women who had PE. After adjustment for apoA-I levels, there was no significant difference in ABCA1-specific efflux between the groups at 6 months postpartum and in normotensive women over time, but remained significantly different between 6 and 24 months in women who had PE. ConclusionsABCA1-mediated CEC is impaired 6 months postpartum after a PE pregnancy and decreases thereafter in both normotensive and PE pregnancies. ABCA1-mediated efflux is dynamic after pregnancy but is unlikely to explain the long-term increased CVD risk in women with PE.

Relationship between the pre-pregnancy BMI, gestational weight gain, and risk of preeclampsia and its subtypes

Objective: To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia. Methods: Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes. Results: Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension (P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m2 and inadequate gestational weight gain were protective factors for PE (OR=0.74, 95%CI: 0.56-0.98; OR=0.78, 95%CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m2 and excessive gestational weight gain were risk factors for PE (OR=1.82, 95%CI: 1.54-2.14; OR=1.82, 95%CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m2 was a protective factor for EOPE and MPE (OR=0.52, 95%CI: 0.32-0.83; OR=0.47, 95%CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE (OR=1.86, 95%CI: 1.51-2.30; OR=1.90, 95%CI: 1.39-2.60) in pregnant women 18.5 kg/m2≤BMI<24.0 kg/m2 and ≥24.0 kg/m2. Inadequate gestational weight gain (OR=0.55, 95%CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m2. Excessive gestational weight gain (OR=4.05, 95%CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m2≤BMI<24.0 kg/m2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE (OR=0.39, 95%CI: 0.19-0.80; OR=0.29, 95%CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE (OR=1.60, 95%CI: 1.06-2.42;OR=2.20, 95%CI: 1.44-3.37;OR=2.28, 95%CI: 1.58-3.29). Conclusions: Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.

Simultaneous use of Tumor Necrosis Factor, Lipid Profile, and β-hCG As Markers of Severity of Preeclampsia.

Tumor necrosis factor, Lipid Profile, and β-hCG are markers that proved to be changed with preeclampsia. We aim to study their combined use as predictors of the severity of preeclampsia. A case-control study was conducted in our University Hospitals on pregnant women complicated by mild or severe PE and healthy normal pregnant women as a control group. Samples of these markers were taken at a gestational age between 28 and 36weeks. A total number of 90 pregnant women were selected. The first group was mild PE (17 cases), the second group was severe PE (28 cases), and the third group was normal pregnant women (control group 45 cases). There is a statistically significant positive correlation between β-hCG, triglycerides, Cholesterol, LDL, VLDL, and Tumor necrosis factor. These markers correlate with the severity of PE. HDL demonstrates a statistically significant negative correlation with TNF-α and β-hCG. There is a strong correlation between the increase of TNF, β-hCG, triglycerides, LDL, and cholesterol in cases of PE. These markers are associated with the severity of PE. These markers can be incorporated into a predictive model for PE.

Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome.

BackgroundPre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.Methodsperipheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.Resultscirculating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P<0.01).ConclusionsAberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.

Pregnancy-induced low serum Ficolin levels may underlie the development of Pre-eclampsia and predict it

Objectives: Estimation of serum ficolin-2 and -3 for normotensive pregnant women to find a relation between ficolin levels and devel- opment of PE. Patients & Methods: Primigravida attending the clinic prior to the 12th gestational week underwent blood pressure (BP) measurements and gave blood sample for estimation of fasting blood glucose (FBG) and ELISA estimation of serum ficolin. Enrolled women were asked to attend 4-weekly for BP measurement; 59 PE women (Group PE), 59 normotensive pregnant women (Group NT) and 59 non-pregnant women (Group NP) were enrolled. Results: At time of PE diagnosis, all pregnant women had higher BP than their baseline measures, with significantly higher measures in PE women. Serum ficolin-2 levels were significantly lower in preg- nant than NP women and in PE than NT women, while serum ficol- in-3 levels were significantly lower in PE than NT women. Devel- opment of PE was positively associated with higher BMI, FBG and BP, while was negatively correlated with ficolin levels. Regression analysis defined low serum ficolin levels as negative predictors for PE development and serum ficolin-2 level Conclusion: Pregnancy has deleterious effect on complement path- way manifested by lower serum ficolin. Low serum ficolin-2 early in pregnancy is a sensitive screening test for pregnant women and can exclude PE development with 100% negative predictive value at level

Platelet Counts and Indices Are Altered in Pre-Eclampsia

BACKGROUND: Endothelial damage and activation of platelets leading to their increased consumption and increase in production of young platelets by bone marrow is the most common pathophysiology of pre-eclampsia. Thus, fall in platelet count and altered platelet indices may have diagnostic as well as prognostic value in pre-eclampsia. AIM: To evaluate platelet count and platelet indices between pre-eclamptic and normotensive women and to assess their association with severity of pre-eclampsia.&#x0D; METHODS: Platelet counts and indices were estimated in 30 normotensive and 30 PE women at 20-24 weeks pregnancy and were repeated after every 4 weeks.&#x0D; RESULTS: Mean platelet counts, platelet volume, platelet distribution width, and platelet large cell ratio between pre-eclampsia and normotensive women were significantly altered in PE women and were associated with severity of PE. This alteration of platelet count and indices occurred even before the rise of BP.&#x0D; CONCLUSION: All the platelet indices were found to be reliable markers of PE and were found to be increased much earlier than BP. MPV had the maximum sensitivity (96.7%) and specificity (93.3%) and was the most reliable biomarker.

Biomarkers of placental redox imbalance in pregnancies with preeclampsia and consequent perinatal outcomes

ObjectiveTo compare redox and inflammatory markers between normal and PE-derived placentas and to evaluate the relationship between placental redox imbalance markers and perinatal outcomes in pregnancies with PE. MethodsThis was a cross-sectional study conducted at the maternity hospital of a university hospital in Maceio-Alagoas, Brazil, in 2017, including women diagnosed with PE and healthy pregnant women and their conceptuses. After screening, standardized questionnaires containing socioeconomic, clinical, obstetric and anthropometric data were applied. After delivery, placental samples were collected for quantification of biomarkers of redox imbalance (catalase – CAT; malondialdehyde – MDA; hydrogen peroxide – H2O2; superoxide dismutase – SOD; reduced glutathione – GSH; oxidized glutathione – GSSG; and their ratio – GSH/GSSG) and inflammation (myeloperoxidase – MPO; interleukin (IL)-6; IL-8; IL-10; and tumor necrosis factor-alpha – TNF-α). All biomarkers were evaluated via linear regression with adjustments of variables with measures of weight, length, head circumference (HC), chest circumference (CC) and gestational age of newborns at birth, considering p < 0.05 as significant. ResultsA total of 100 pregnant women with PE and 50 healthy pregnant women were studied. Higher placental levels of catalase (p = 0.018), SOD (p = 0.031), the GSH/GSSG ratio (p = 0.019) and IL-6 (p = 0.010) and lower GSSG (p = 0.001) were observed in pregnant women with PE than in the control group. Positive associations between placental GSH levels and body weight, HC, CC and gestational age at birth (p < 0.05) were identified. ConclusionPE-derived placentas had high concentrations of some antioxidants (enzymes and thiols), which might be a compensation mechanism against oxidative stress. Placental GSH levels were the only biomarker, among the studied ones, related positively with beneficial perinatal outcomes, suggesting that this endogenous antioxidant plays an important role in maintaining the health of the conceptus and women with PE.

Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation

ObjectivePre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis...

Analysis of polymorphisms, promoter methylation, and mRNA expression profile of maternal and placental P53 and P21 genes in preeclamptic and normotensive pregnant women

BackgroundPreeclampsia (PE), as a multisystem disorder, is associated with maternal hypertension and proteinuria. Apoptosis seems to be involved in the pathophysiology of PE, although its precise pathogenic mechanisms are not well established. In this study, we aimed to identify the association between maternal TP53-rs1042522, P21-rs1801270, and P21-rs1059234 polymorphisms and PE. In addition, we examined the effects of promoter methylation and TP53 and P21 polymorphisms on placental mRNA expression in PE women.MethodsThe blood of 226 PE women and 228 normotensive pregnant women was examined in this study. In addition, the placentas were genotyped in 109 PE and 112 control women. The methylation status was assessed by a methylation-specific PCR assay, while mRNA expression was examined via Quantitative Real Time PCR.ResultsThe maternal and placental P21-rs1801270 CA genotype had a significant association with the reduced risk of PE. In the dominant, recessive, and allelic models, maternal/placental P21-rs1059234 polymorphism had no statistically significant association with the risk of PE. On the other hand, the reduced risk of PE was associated with maternal, but not placental TP53-rs1042522 polymorphism in the dominant and recessive models. The maternal and placental P21-rs1801270 polymorphism was associated with PE risk. The maternal P21 Trs1059234Crs1801270 haplotype was associated with 3.4-fold increase in PE risk, However the maternal P21 Trs1059234Ars 1801270 haplotype and placental Crs1059234CA rs1801270 haplotype led to 0.5 and 0.4-fold decrease in PE risk, respectively. PE women showed 5.6 times higher levels of placental mRNA expression of TP53 gene, although it was not associated with rs1042522 polymorphism. The relative placental mRNA expression of P21 gene was 0.2 in PE women. It was also 2.4 times higher in individuals with rs1801270CA genotype than those with AA genotype. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a 3.4-fold and 3-fold increase in PE risk, respectively. However, no association was found between P21 and TP53 mRNA expression and promoter methylation.ConclusionIn conclusion, P21-rs1801270 and TP53-rs1042522 polymorphisms were involved in reduced risk of PE. P21-rs1801270 was associated with decreased P21 mRNA expression. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a higher PE risk.

Polymorphisms within vitamin D binding protein gene within a Preeclamptic South African population

ABSTRACTObjectives: The vitamin D binding protein encoded by the GC gene contains two single nucleotide polymorphisms (rs4588 and rs7041) that have been associated with disease outcome, these include periodontitis coronary heart disease and hypertension. In pregnancy, these SNPs influence vitamin D metabolism that could result in hypertensive disorders such as PE. The etiology of PE, still remains elusive. The aim of this study was to evaluate the distribution of rs4588 and rs7041 within the GC gene among PE and normotensive pregnant women, residing in Durban, KwaZulu-Natal, South Africa.Study design: Our study consisted of n = 600 participants (normotensive (n = 246, N); early onset PE (n = 167, EOPE); and late-onset PE (n = 246, LOPE)). We extracted DNA from whole blood and genotyped for rs4588 and rs7041 SNPs using the TaqMan assay.Results: Regardless of HIV status, we observed the rs4588 (CC genotype) more frequently in PE (EOPE+LOPE) compared to the normotensive participants with an OD ratio of 0.74 (95% CI, 0.35–1.5; p < 0.001). We report a significant difference in the frequency of rs7041 (GT genotype) in the EOPE group compared to the normotensive group with an OD ratio of 11.48 (95% CI, 2.6–103.7; p < 0.001). The rs7041 GT genotype had a higher frequency in the EOPE compared to the LOPE group, with an OD ratio of 15.15 (95% CI, 2.3–639.2; p < 0.001).Conclusion: This is the first study to describe the prevalence of SNPs of the rs4588 and rs7041 within the GC gene in women with PE within the high HIV endemic area of KZN, South Africa. Notably, a significant association of the rs7041 (TT genotype) and rs4588 (CC genotype) occurred at a higher frequency in PE compared to the normotensive cohort. Future studies will examine the functional effect of the GC region in relation to pregnancy and vitamin D deficiency.

RETRACTED ARTICLE: lncRNA TUG1 modulates proliferation, apoptosis, invasion, and angiogenesis via targeting miR-29b in trophoblast cells

BackgroundPre-eclampsia (PE) is regarded as the leading cause of maternal and neonatal morbidity and mortality. Nevertheless, the potential mechanism for the regulation of trophoblast behaviors and the pathogenesis of PE remain largely elusive. Recently, accumulating evidence emphasized that aberrant expression of long non-coding RNAs (lncRNAs) functions as imperative regulators in human diseases, including PE. Thus, identifying PE-related specific lncRNAs to uncover the underlying molecular mechanism is of much significance. However, the functional roles and underlying mechanisms of lncRNAs in PE progression remain unclear.MethodPlacenta tissues obtained from patients with PE and healthy pregnant women were performed to measure TUG1 expression by qRT-PCR analysis. Transient transfections were conducted to alter TUG1 expression. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were carried out to assess cell proliferation and apoptosis, respectively. Transwell and tube formation assays were performed to measure the capacity of cell invasion and angiogenesis. Moreover, the luciferase reporter assay was subjected to verify the binding relationship between TUG1 and miR-29b. Western blot analysis was performed to detect the expression of key proteins in the PI3K/AKT and ERK pathway.ResultsHere, we identified a lncRNA, TUG1, which was notably decreased in placental samples of PE patients. Functional experiments of loss- or gain-of-function assays also verified that ectopic expression of TUG1 promoted cell proliferation, invasion, and angiogenesis, but negatively regulated cell apoptosis, whereas TUG1 inhibition presented the opposite effects. Furthermore, mechanistic researches revealed that TUG1 could act as a molecular sponge for miR-29b, thus regulating MCL1, VEGFA, and MMP2 to modulate PE development.ConclusionsTaken together, our findings demonstrated that TUG1 exerts as a critical role in PE progression, which might furnish a novel therapeutic marker for PE treatment.

Estimation of Umbilical Artery Resistive Index in Pregnant Women with Preeclampsia in Al-Najaf Province

This study was carried out on 105 pregnant women with preeclampsia in addition to 105 pregnant women without preeclampsia as a control at Al-Najaf province from September ,2017-May 2018. All the included patients were examined by Doppler study to assess the resistive index of umbilical artery RI in preeclamptic pregnant patients with PE and pregnant women without PE. The results reveals that there was significant difference of umbilical artery RI 0.658±0.304, concerning preeclamptic pregnant patients in comparison to pregnant women without PE(0.571±0.215) , ( PV lesser than0.05) . &#x0D; In addition to that the umbilical artery RI was (0.577±0.301) in preeclamptic pregnant patient with mild PE while it was (0.813±0.247) in preeclamptic pregnant patient with severe PE which displayed a statistically significant difference( PV less than0.05).Also this study showed that the umbilical artery RI in preeclamptic pregnant patients with H. pylori was(1.11±0.319) which was greater than that for preeclamptic pregnant patients without H. pylori (0.919±0.25) with a statistically significant difference ( PV less than 0.5). It was concluded that Umbilical artery resistive index is a useful parameter in detection of preeclampsia and its severity and the umbilical artery resistive index might be useful parameter in prediction of infection of positive H. pylori infection associated with preeclampsia.

Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia.

The current study examined the effects of BAX and BCL2 polymorphisms and methylation as well as mRNA expression on susceptibility to PE. After delivery, the placentas were collected from 92 women with PE, as well as 106 normotensive pregnant women. The BAX rs4645878 and BCL2 rs2279115 polymorphisms were genotyped by the PCR-RFLP method. Methylation-specific PCR (MSP) was used for analysis of promoter methylation. mRNA expression was assayed by Quantitative RT-PCR. In addition, in silico analysis was performed by bioinformatics tools. There was no relationship between PE and placental BAX rs4645878 and BCL2 rs2279115 polymorphisms. The groups were not significantly different regarding the promoter methylation of BAX gene. Nonetheless, the MM status of BCL2 promoter had a significantly higher frequency in the PE group and was associated with 2.7-fold higher risk of PE (OR=2.7, 95% CI=1.3-5.6; P = 0.01). The relative mRNA expression of BCL2 was decreased in the placentas of PE women (P < 0.0001). The expression of BAX gene was not significantly different between the two groups. There was no association between placental BAX rs4645878 and BCL2 rs2279115 polymorphisms and mRNA expression levels. In silico analysis indicated that BAX rs4645878 and BCL2 rs2279115 polymorphisms were located in the core recognition site of different transcription factors and these substitutions of wild allele resulted in the loss and/ or change of these binding sites and subsequently may alter BCL2 and BAX expression. This study showed that the BAX and BCL2 polymorphisms and BAX promoter methylation were not associated with PE risk. The BCL2 promoter methylation was associated with lower BCL2 expression and higher PE susceptibility.

MicroRNA-423–5p inhibits the progression of trophoblast cells via targeting IGF2BP1

IntroductionPreeclampsia (PE) is one of the leading causes of maternal and fetal mortality globally. The imbalance of trophoblast homeostasis is closely linked with the pathogenesis of PE. MicroRNA-423–5p (miR-423–5p) has been reported to be abnormally expressed in placenta and blood plasma of pregnant women with PE. In the present study, miR-423–5p expression in blood plasma of pregnant women with PE and healthy pregnant women was detected. Also, the roles and molecular mechanisms of miR-423–5p in the development of trophoblast cells were further investigated. MethodsExpression of miR-423–5p and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) mRNA was detected by RT-qPCR assay. Protein expression of IGF2BP1, Bcl-2 and Bax was determined using western blot assay. Cell migratory and invasive capacities were assessed by transwell migration and invasion assay. Cell apoptotic rate was determined using flow cytometry via the double-staining of Annexin V-FITC/Propidium Iodide. The interaction between miR-423–5p and IGF2BP1 was demonstrated by bioinformatics analysis and luciferase reporter assay. ResultsMiR-423–5p was highly expressed in blood plasma of pregnant women with PE. MiR-423–5p inhibited migration, invasion and proliferation as well as induced apoptosis in HTR-8/SVneo cells. Further investigation revealed that IGF2BP1 was a target of miR-423–5p. Moreover, IGF2BP1 overexpression promoted migration, invasion and proliferation, suppressed apoptosis, and weakened miR-423–5p function in HTR-8/SVneo cells. DiscussionMiR-423–5p inhibited migration, invasion and proliferation as well as induced apoptosis by targeting IGF2BP1 in HTR-8/SVneo cells, presenting a novel molecular basis implicated in PE pathogenesis.