Etiology Of Preeclampsia Research Articles

Evaluation of the Human Placental Microbiota in Early- and Late-Onset Pre-Eclampsia.

Despite many decades of research, the exact etiology of pre-eclampsia (PE) remains unknown. Several etiopathologies have been suggested, including the role of the placental microbiota. However, the existence of placental microbiota and its possible contribution to pregnancy complications, particularly PE has remained controversial. The present study was designed to identify different microbes that co-exist the placenta of women with early- and late-onset PE. Thirty age-matched normotensive and early-onset as well as age-matched normotensive and late-onset pre-eclamptic women respectively, were recruited. After obtaining an informed consent, the placental tissues were obtained through caesarian section with sterile and standardized clinical procedures. DNA was extracted from each tissue and microbiome analysis was conducted using a targeted 16S analysis and the reads were analyzed with bioinformatics. There was a significance difference between the blood pressure of early-/late-onset PE compared with age-matched normotensive controls, respectively. In addition, the reads from placencental samples were classified as belonging to the phyla, Actinobacteria, Firmicutes, Bacteroidetes, Proteobacteria, with Proteobacteria dominated by the classes Pseudomonadales and Gammaproteobacteria with smaller amounts of Actinobacteria and Bacteroidetes. There was no significant difference between the placental bacterial species of early-/late-onset PE compared with age-matched normotensive controls, respectively. Further analysis found no correlation between bacterial species and early- or late-onset PE. The present results demonstrate a low biomass of bacterial species, which might further indicate that the placental samples had very low levels of bacteria species and there is no correlation between the bacterial composition and early- or late-onset PE.

Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.

Preeclampsia, a pregnancy disorder characterized by de novo hypertension and maternal multisystem organ dysfunction, is the leading cause of maternal mortality worldwide and is associated with a fourfold greater risk of cardiovascular disease throughout the lifespan. Current understanding of the etiology of preeclampsia remains unclear, due in part to the varying phenotypical presentations of the disease, which has hindered the development of effective and mechanism-specific treatment or prevention strategies both during and after the affected pregnancy. These maternal sequelae of preeclampsia are symptoms of systemic vascular dysfunction in the maternal nonreproductive microvascular beds that drives the development and progression of adverse cardiovascular outcomes during preeclampsia. Despite normalization of vascular disturbances after delivery, subclinical dysfunction persists in the nonreproductive microvascular beds, contributing to an increased lifetime risk of cardiovascular and metabolic diseases and all-cause mortality. Given that women with a history of preeclampsia demonstrate vascular dysfunction despite an absence of traditional CVD risk factors, an understanding of the underlying mechanisms of microvascular dysfunction during and after preeclampsia is essential to identify potential therapeutic avenues to mitigate or reverse the development of overt disease. This article aims to provide a summary of the existing literature on the pathophysiology of maternal microvascular dysfunction during preeclampsia, the mechanisms underlying the residual dysfunction that remains after delivery, and current and potential treatments both during and after the affected pregnancy that may reduce microvascular dysfunction in these high-risk women. © 2024 American Physiological Society. Compr Physiol 14:5703-5727, 2024.

CoCl2-mimicked hypoxia induces the assembly of stress granules in trophoblast cells via eIF2α phosphorylation-dependent and -independent pathways.

Hypoxia has been implicated in preeclampsia (PE) pathophysiology. Stress granules (SGs) are present in the placenta of patients with PE. However, the pathways that contribute to SG aggregation in PE remain poorly understood. The objective of the current study is to investigate this issue. We first established an in vitro hypoxia model using human trophoblast cell line HTR-8/SVneo treated with cobalt chloride (CoCl2). CCK8 assay and wound healing assay were conducted to assess the viability and migration of HTR-8/SVneo cells after exposure to CoCl2-mimicked hypoxia. SG component expression in HTR-8/SVneo cells treated with CoCl2 alone, or in combination with indicated siRNAs was evaluated by reverse transcription quantitative PCR (RT-qPCR), western blot and immunofluorescence staining. Our results found CoCl2-mimicked hypoxia inhibits the proliferation and migration of HTR-8/SVneo cells. The treatment of CoCl2 can induce SG assembly in HTR-8/Svneo cells. Mechanistically, both heme-regulated inhibitors (HRI) mediated eukaryotic translation initiation factor (eIF)2α phosphorylation pathway and 4E binding protein 1 (4EBP1) pathway are involved in SG formation under the stress of CoCl2-mimicked hypoxia. Hypoxia-induced SGs in trophoblast cells might contribute to the etiology of PE.

Oxidative Stress and Anti-Carbonic Anhydrase Antibody Levels in Early Preeclampsia: A Clinical Investigation

Objective: Preeclampsia (PE) is a dangerous condition that affects 3–5% of pregnancies and has a substantial risk of death and morbidity for both mothers and newborns. The processes behind the etiology of PE are not entirely known, despite the fact that it is the primary cause of illness and death among mothers globally. In order to further understand the correlations between these parameters, this study will look at the levels and presence of anti-carbonicianhydrase (CA) I and II antibodies, total oxidanticapacity (TOC), total antioxidanticapacity (T-AOC), and malondialdehyde (MDA) in early PE. Methods: The research analyzed 30 pregnant women with early PE and 30 normal pregnant women as the control group. Serumxlevels of anti-CAiI (pg/mL), anti-CAxII (ng/mL), MDA (nmol/mL), TOS (U/mL), T-AOC (U/mL) were measured and compared between the two groups. Results: Significant variations were noted in the amount of anti-CA I, anti-CA II, MDA, TOS, and T-AOC (both p

Causal pathways in preeclampsia: a Mendelian randomization study in European populations.

Our study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality. Employing the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran's Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification. Our analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses. This extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

Placental Origins of Preeclampsia: Insights from Multi-Omic Studies.

Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality worldwide, with the placenta playing a central role in disease pathophysiology. This review synthesizes recent advancements in understanding the molecular mechanisms underlying PE, focusing on placental genes, proteins, and genetic variants identified through multi-omic approaches. Transcriptomic studies in bulk placental tissue have identified many dysregulated genes in the PE placenta, including the PE signature gene, Fms-like tyrosine kinase 1 (FLT1). Emerging single-cell level transcriptomic data have revealed key cell types and molecular signatures implicated in placental dysfunction and PE. However, the considerable variability among studies underscores the need for standardized methodologies and larger sample sizes to enhance the reproducibility of results. Proteomic profiling of PE placentas has identified numerous PE-associated proteins, offering insights into potential biomarkers and pathways implicated in PE pathogenesis. Despite significant progress, challenges such as inconsistencies in study findings and lack of validation persist. Recent fetal genome-wide association studies have identified multiple genetic loci associated with PE, with ongoing efforts to elucidate their impact on placental gene expression and function. Future directions include the integration of multi-omic data, validation of findings in diverse PE populations and clinical subtypes, and the development of analytical approaches and experimental models to study the complex interplay of placental and maternal factors in PE etiology. These insights hold promise for improving risk prediction, diagnosis, and management of PE, ultimately reducing its burden on maternal and neonatal health.

Hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

Alpinumisoflavone ameliorates H2O2-induced intracellular damages through SIRT1 activation in pre-eclampsia cell models

Pre-eclampsia (PE) is classified as pregnancy-specific hypertensive disease and responsible for severe fetal and maternal morbidity and mortality, which influenced an approximate 3 ∼ 8 % of all pregnancies in both developed and developing countries. However, the exact pathological mechanism underlying PE has not been elucidated and it is urgent to find innovate pharmacotherapeutic agents for PE. Recent studies have reported that a crucial part of the etiology of PE is played by placental oxidative stress. Therefore, to treat PE, a possible treatment approach is to mitigate the placental oxidative stress. Alpinumisoflavone (AIF) is a prenylated isoflavonoid originated in mandarin melon berry called Cudrania tricuspidate, and is well known for its versatile pharmacotherapeutic properties, including anti-fibrotic, anti-inflammatory, anti-tumor, and antioxidant activity. However, protective property of AIF on extravillous trophoblast (EVT) under placental oxidative stress has not been elucidated yet. Therefore, we assessed stimulatory effects of AIF on the viability, invasion, migration, mitochondria function in the representative EVT cell line, HTR-8/SVneo cell. Moreover, protective activities of AIF from H2O2 were confirmed, in terms of reduction in apoptosis, ROS production, and depolarization of mitochondrial membrane. Furthermore, we confirmed the direct interaction of AIF with sirtuin1 (SIRT1) using molecular docking analysis and SIRT1-mediated signaling pathways associated with the protective effects of AIF on HTR-8/SVneo cells under oxidative stress. Finally, beneficial efficacy of AIF against oxidative stress was further confirmed using BeWo cells, syncytiotrophoblast cell lines. These results suggest that AIF may ameliorate H2O2-induced intracellular damages through SIRT1 activation in human trophoblast cells.

Evaluating the role of DNA methyltransferases in trophoblast fusion and preeclampsia development: Insights from methylation-regulated genes.

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.

Zinc, antioxidant enzymes in preeclampsia, and association with newborn outcome

BackgroundThe etiology of preeclampsia (PE) may be associated with the increased of production of reactive species and decreased antioxidant activity of enzymes. Inadequate intake of Zn can affect gestational health due to its biological functions, such as its role in the antioxidant defense system. The study aimed to assess the nutritional status of Zn and antioxidant enzymes in postpartum women and its correlation with neonatal outcomes. MethodsA cross-sectional analytical study was carried out at a referral gynecology and obstetrics hospital. A total of 119 women (PE = 58, HP = 61) participated in the study. A quantitative food-frequency questionnaire was used to assess food consumption and further analyze the dietary Zn levels.Zinc levels in plasma and erythrocytes samples were analyzed by flame atomic absorption spectrometry, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by UV-Vis spectrophotometry. ResultsPlasma and dietary intake Zn results were considered adequate and without statistical difference between groups. SOD levels were significantly higher in the HP group (p = 0.011), and CAT levels were higher in the PE group (p = 0.050). There was a positive correlation between SOD activity in women with PE and the weight of their newborns (r = 0.336, p=0.021). ConclusionThe results showed adequate Zn levels (consumption and serum levels) in the groups studied, although with a reduction of plasma Zn in the PE group compared to the PH group.Zinc in plasma fractions and erythrocytes are important markers for oxidative stress, in particular, plasma Zn seems to be related to the rapid response to preeclampsia. The activity of antioxidant enzymes was elevated in the groups studied. Better SOD activity improves birth weight in children of pregnant women with preeclampsia.

Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy

The etiology of preeclampsia (PE), a severe complication of pregnancy with several clinical manifestations and a high incidence of maternal and fetal morbidity and mortality, remains unclear. This issue is a major hurdle for effective treatment strategies. We recently demonstrated that PE exhibits an Alzheimer-like etiology of impaired autophagy and proteinopathy in the placenta. Targeting of these pathological pathways may be a novel therapeutic strategy for PE. Stimulation of autophagy with the natural disaccharide trehalose and its lacto analog lactotrehalose in hypoxia-exposed primary human trophoblasts restored autophagy, inhibited the accumulation of toxic protein aggregates, and restored the ultrastructural features of autophagosomes and autolysosomes. Importantly, trehalose and lactotrehalose inhibited the onset of PE-like features in a humanized mouse model by normalizing autophagy and inhibiting protein aggregation in the placenta. These disaccharides restored the autophagy-lysosomal biogenesis machinery by increasing nuclear translocation of the master transcriptional regulator TFEB. RNA-seq analysis of the placentas of mice with PE indicated the normalization of the PE-associated transcriptome profile in response to trehalose and lactotrehalose. In summary, our results provide a novel molecular rationale for impaired autophagy and proteinopathy in patients with PE and identify treatment with trehalose and its lacto analog as promising therapeutic options for this severe pregnancy complication.

Excessive ER-phagy mediated by FAM134B contributes to trophoblast cell mitochondrial dysfunction in preeclampsia.

Autophagy dysregulation and Ca 2+-induced mitochondrial dysfunction in trophoblast cells are proposed to contribute to preeclampsia (PE) development. FAM134B is identified as a receptor associated with endoplasmic reticulum autophagy (ER-phagy). In this study, the placentas of normal pregnant women and PE patients are collected and analyzed by immunohistochemistry, quantitative real-time PCR, and western blot analysis. The effects of ER-phagy are investigated in HTR8/SVneo cells. Significantly increased levels of FAM134B, inositol-1,4,5-triphosphate receptor type 1 (IP3R), calnexin, cleaved caspase 3 and cytochrome C are detected in the PE placenta and sodium nitroprusside (SNP)-treated HTR-8/SVneo cells. Overexpression of FAM134B in HTR-8/SVneo cells results in increased apoptosis, impaired invasion capacity, and diminished mitochondrial function, while an autophagy inhibitor improves mitochondrial performance. Excessive ER-phagy is also associated with an increased concentration of gamma linolenic acid. Our findings suggest that FAM134B contributes to trophoblast apoptosis by mediating ER-mitochondria Ca 2+ transfer through mitochondria-associated endoplasmic reticulum membranes (MAMs) and subsequent mitochondrial function, further enhancing our understanding of PE etiology.

Implication of viruses in the etiology of preeclampsia.

Preeclampsia is one of the most common disorders that poses threat to both mothers and neonates and a major contributor to perinatal morbidity and mortality worldwide. Viral infection during pregnancy is not typically considered to cause preeclampsia; however, syndromic nature of preeclampsia etiology and the immunomodulatory effects of viral infections suggest that microbes could trigger a subset of preeclampsia. Notably, SARS-CoV-2 infection is associated with an increased risk of preeclampsia. Herein, we review the potential role of viral infections in this great obstetrical syndrome. According to in vitro and in vivo experimental studies, viral infections can cause preeclampsia by introducing poor placentation, syncytiotrophoblast stress, and/or maternal systemic inflammation, which are all known to play a critical role in the development of preeclampsia. Moreover, clinical and experimental investigations have suggested a link between several viruses and the onset of preeclampsia via multiple pathways. However, the results of experimental and clinical research are not always consistent. Therefore, future studies should investigate the causal link between viral infections and preeclampsia to elucidate the mechanism behind this relationship and the etiology of preeclampsia itself.

Exploring the role of exosomal MicroRNAs as potential biomarkers in preeclampsia.

The complex pathogenesis of preeclampsia (PE), a significant contributor to maternal and neonatal mortality globally, is poorly understood despite substantial research. This review explores the involvement of exosomal microRNAs (exomiRs) in PE, focusing on their impact on the protein kinase B (AKT)/hypoxia-inducible factor 1-α (HIF1α)/vascular endothelial growth factor (VEGF) signaling pathway as well as endothelial cell proliferation and migration. Specifically, this article amalgamates existing evidence to reveal the pivotal role of exomiRs in regulating mesenchymal stem cell and trophoblast function, placental angiogenesis, the renin-angiotensin system, and nitric oxide production, which may contribute to PE etiology. This review emphasizes the limited knowledge regarding the role of exomiRs in PE while underscoring the potential of exomiRs as non-invasive biomarkers for PE diagnosis, prediction, and treatment. Further, it provides valuable insights into the mechanisms of PE, highlighting exomiRs as key players with clinical implications, warranting further exploration to enhance the current understanding and the development of novel therapeutic interventions.

Endothelial Nitric Oxide synthase (eNOS) in Preeclampsia: An Update.

Preeclampsia (PE) is a common pregnancy-related hypertensive disorder and is a leading cause of maternal and perinatal morbidity and mortality. The incidence of PE and its associated health care costs have been increasing in the United States over the past three decades. Pregnancies complicated by PE put both the mother and child at increased risk for chronic illnesses such as cardiovascular disease, cerebrovascular disease, and cognitive impairment later in life. To date, there is no effective treatment for PE and the etiology of PE is largely unknown. While human epidemiological studies have established an association between various genetic factors and PE, a causative link between genes associated with PE and PE development has been difficult to establish. Human studies have shown that variants in eNOS (endothelial nitric oxide synthase, also known as NOS3) gene are associated with PE, and animal experimental studies have provided evidence to show the potential functional connection between the eNOS gene and PE. Here we review several studies that investigated the role of eNOS in PE, as well as studies that described how manipulating the eNOS/NO pathway could aid in disease intervention.

Psychosocial and Perceived Stress Associated with Pre-eclampsia in a Periurban Hospital

Pre-eclampsia complicates about 2% of pregnancy Exact aetiology of Pre-eclampsia is not known, however a number of psychosocial factors are often found to be associated with it. The purpose of the study was to ascertain the prevalence of psychosocial factors and perceived stress among patients with Pre-eclampsia. This was a cross sectional study done at institute of child and mother health during July to September, 2015. Total 71 women admitted for delivery with diagnosis of Preeclampsia were interviewed in the postnatal ward within three days of delivery using a structured questionnaire. Informed consent was taken. Data analyzed using SPSS version 22. Mean age was 23.9± 4.3 years with a range of 18-36 years, about a quarter were illiterate. Majority of them stay within extended family and mean household family member was 6.25± 1.93 about 77.5% of husbands were smokers, history of abortion was present in 21.1%. More than half of them have history of hypertension or diabetes in the family. Mean Systolic BP was 122.6±21.3 and mean diastolic BP was 83.5±14.6. About 42.2% reported that their family members were not aware of need of proper nutrition during pregnancy rather were indifferent. Ability to spend money by her was limited, sometimes by 33.8%, 28.2% if they ask for and 36.6% never have the opportunity. On recall of last one month period a significant proportion of women stated that they felt to be stressed sometimes during pregnancy. Risk factors for Preeclampsia like family history of Hypertension and Diabetes, passive smoking, low education level was found quite prevalent among women with pre-eclampsia. Majority of women reported to experience moderate stress and prevalence of stress was more among 19-24 years age group. Bangladesh J Obstet Gynaecol, 2022; Vol. 37(2): 119-126

Elevated gestational testosterone impacts vascular and uteroplacental function

Maternal vascular adaptations to establish an adequate blood supply to the uterus and placenta are essential for optimal nutrient and oxygen delivery to the developing fetus in eutherian mammals, including humans. Numerous factors contribute to maintaining appropriate hemodynamics and placental vascular development throughout pregnancy. Failure to achieve or sustain these pregnancy-associated changes in women is strongly associated with an increased risk of antenatal complications, such as preeclampsia, a hypertensive disorder of pregnancy. The precise etiology of preeclampsia is unknown, but emerging evidence points to a potential role for androgens. The association between androgens and maternal cardiovascular and placental function merits particular attention due to the notable 2- to 3-fold elevated plasma testosterone (T) levels observed in preeclampsia. T levels in preeclamptic women positively correlate with vascular dysfunction, and preeclampsia is associated with increased androgen receptor (AR) levels in placental tissues. Moreover, animal studies replicating the pattern and magnitude of T increase observed in preeclamptic pregnancies have reproduced key features of preeclampsia, including gestational hypertension, endothelial dysfunction, heightened vasoconstriction to angiotensin II, impaired spiral artery remodeling, placental hypoxia, reduced nutrient transport, and fetal growth restriction. Collectively, these findings suggest that AR-mediated activity plays a significant role in the clinical presentation of preeclampsia. This review critically evaluates this hypothesis, considering both clinical and preclinical evidence.

Association between expression levels of p53, miRNA-21, and lncRNA-TCL6 and the risk of preeclampsia in pregnant women

BackgroundPreeclampsia is a hypertensive pregnancy-related disorder. The etiology of preeclampsia is still not fully elucidated. Genetic factors are suggested to play a vital role. AimThe association between p53, miRNA-21, and lncRNA-TCL6 expression levels and the risk of preeclampsia and its onset and severity in pregnant women was evaluated. MethodExpression levels of the analyzed RNAs were assessed in the serum samples from 75 preeclamptic pregnant women and 75 volunteer pregnant women with an uncomplicated pregnancy. ResultsCases showed upregulated p53, lnc-TCL6, and downregulated miRNA-21. P53 expression and preeclampsia severity were substantially correlated, while miRNA-21 and lnc-TCL6 were not. None of them was associated with preeclampsia onset. In diagnosing preeclampsia, p53 had the best sensitivity (98.67 %), followed by miRNA-21 (97.33 %) and lnc-TCL6 (92 %). P53 had the highest sensitivity (68.42 %) for distinguishing mild from severe cases. Lnc-TCL6 exhibited 52.63 % sensitivity, while miRNA-21 had 52.63 % sensitivity. Finally, for discriminating early and late-onset cases, miRNA-21 demonstrated the highest sensitivity (66 %), followed by p53 (62 %) and lnc-TCL6 (54 %). P53 expression was inversely correlated with proteinuria. Parity, TLC, platelet count, AST, and ALT were positively correlated, while lnc-TCL6 expression was negatively correlated with miRNA-21 expression. However, parity negatively correlated with lnc-TCL6 expression. ConclusionP53, miRNA-21, and lnc-TCL6 were dysregulated in preeclampsia compared to normal pregnancy, highlighting the role of apoptosis in its development. P53 can be a prognostic marker for preeclampsia, discriminating between mild and severe cases.

Missing links in preeclampsia cell model systems of endothelial dysfunction

Preeclampsia, one of the main hypertensive disorders of pregnancy, is associated with circulating factors released by the ischemic placenta accompanied by systemic endothelial dysfunction. The etiology of preeclampsia remains poorly understood although it is associated with high maternal and fetal mortality and increased cardiovascular disease risk. Most cell model systems used for studying endothelial dysfunction have not taken into account hemodynamic physical factors such as shear-stress forces which may prevent extrapolation of cell data to in vivo settings. We overview the role of hemodynamic forces in modulating endothelial cell function and discuss strategies to reproduce this biological characteristic in vitro to improve our understanding of endothelial dysfunction associated with preeclampsia.

Vitamin D deficiency and pregnancy outcome: Does it have a role in preeclampsia etiology?

Purpose: Vitamin D deficiency is higher in pregnancy and there is evidence on its relationship with various obstetric disorders. The aim of this study was to investigate the association between preeclampsia and vitamin D levels in pregnant women. 
 Methods: This study included 1209 women. General characteristics, laboratory results and obstetric outcomes were evaluated. As globally accepted vitamin D deficiency was defined as