Etiology Of Preeclampsia Research Articles

Plasma drop and thin-film revealed distinguished molecular structure in pre-eclampsia: An investigation using synchrotron Fourier-transform infrared microspectroscopy

Pre-eclampsia (PE) is a serious pregnancy-related disorder and the leading cause of maternal and fetal mortality and morbidity worldwide. The etiology of PE is poorly understood and a definitive diagnosis is still lacking. Herein, we used synchrotron-FTIR microspectroscopy as a new analytical tool to investigate the molecular changes in the structure and intensity of lipids (spectral range 3050–2800 cm−1) and protein-carbonyl (spectral range 1855–1485 cm−1) components of the plasma and link them to the pathogenesis of the disease. In the lipid region, an increase in the CH2 and CH3 peaks intensity was noticed in PE group compared to normotensive pregnancy reflecting abnormalities in the lipid profile and a high level of LDL. Increased CH2/CH3 ratio and red shifts were observed in the lipid region in PE highlighting structural variations of lipids and transformation of conformation of lipid tails. In the protein-carbonyl region, a decrease in the amide I and II absorption signals in the plasma of PE compared to normotensive controls was evident, and a red shift was noticed in the amide I region reflecting conformational changes and rearrangement in the α-helix secondary structure of the protein. Moreover, malondialdehyde level and lipid carbonyl peak at 1743 cm−1 were higher and more intense in PE due to the oxidative stress condition in PE. Spectral analysis of plasma drop from PE revealed that lipid and protein components tend to concentrate more in the central region of the drop, and that the most intense wavenumber values for the lipid and amide I region in the plasma drop were very comparable to their analogous in plasma film. Taken together, the current work provides evidence of the promising role of synchrotron-FTIR microspectroscopy in providing a better understanding of the pathophysiology of PE.

Increased Risk of Preeclampsia in Women With a Genetic Predisposition to Elevated Blood Pressure.

Background:Preeclampsia causes significant maternal and perinatal morbidity. Genetic factors seem to affect the onset of the disease. We aimed to investigate whether the polygenic risk score for blood pressure (BP; BP-PRS) is associated with preeclampsia, its subtypes, and BP values during pregnancy.Methods:The analyses were performed in the FINNPEC study (Finnish Genetics of Pre-Eclampsia Consortium) cohort of 1514 preeclamptic and 983 control women. In a case-control setting, the data were divided into percentiles to compare women with high BP-PRS (HBP-PRS; >95th percentile) or low BP-PRS (≤5th percentile) to others. Furthermore, to evaluate the effect of BP-PRS on BP, we studied 3 cohorts: women with preeclampsia, hypertensive controls, and normotensive controls.Results:BP values were higher in women with HBP-PRS throughout the pregnancy. Preeclampsia was more common in women with HBP-PRS compared with others (71.8% and 60.1%, respectively; P=0.009), and women with low BP-PRS presented with preeclampsia less frequently than others (44.8% and 61.5%, respectively; P<0.001). HBP-PRS was associated with an increased risk for preeclampsia (odds ratio, 1.7 [95% CI, 1.1–2.5]). Furthermore, women with HBP-PRS presented with recurrent preeclampsia and preeclampsia with severe features more often.Conclusions:Our results suggest that HBP-PRS is associated with an increased risk of preeclampsia, recurrent preeclampsia, and preeclampsia with severe features. Furthermore, women with HBP-PRS present higher BP values during pregnancy. The results strengthen the evidence pointing toward the role of genetic variants associated with BP regulation in the etiology of preeclampsia, especially its more severe forms.

Increasing of LDH Specific Activity and PEPCK Level Play a Role on Activation of Gluconeogenesis Pathway in Early Onset Pre-Eeclampsia Placenta.

Recent advancement on experiment concluded that etiology of pre-eclampsia (PE) could be explained by the "two-stage" theory. The theory of which explained that pre-eclampsia occurs due to abnormalities in spiral arteries development and release of inflammatory response. Failure of spiral arteries development, the lesion of damage could be due to ischemia-reperfusion or hypoxia-reoxygenation. Hypoxia in pre-eclamptic placenta leads to metabolic change to anaerobic in glycolysis. Lactate dehydrogenase (LDH) has important role in anaerobic glycolysis that catalyzes the conversion of lactate to pyruvate during hypoxia. On the other hand, phosphoenolpyruvate carboxy kinase (PEPCK) is merely an enzyme of gluconeogenesis. This research conduct to reveal that in early onset pre-eclampsia the placenta still hypoxic and undergoes gluconeogenesis even after delivery, through metabolic enzyme of LDH and PEPCK level. This cross-sectional study compared early onset PE (< 34 weeks) with normal term placenta. We measured LDH enzyme activity using colorimetric assay and PEPCK protein using ELISA method. Result show that placental LDH specific activity was increased significantly in PE with median 2.750 (0.030 - 5.680) U/mg compared to normal term placenta 0.255 (0.032 - 1.194) U/mg (Mann-Whitney, p< 0.001). PEPCK level was significantly increased in PE 8.998 (1.737-44.914) ng/mg compared to normal term placenta 1.552 (0.741-8.832) ng/mg (Mann-Whitney, p< 0.001). We conclude that anaerobic glycolysis and gluconeogenesis pathway are increased in early onset PE placenta as adaptation mechanism to hypoxic condition.

Excessive Immune Activation and the Correlation with Decreased Expression of PD-1 at the Maternal-Fetal Interface in Preeclampsia.

The etiology of preeclampsia (PE) is still unknown, and excessive immune activation is an important component of its pathogenesis. Programmed cell death protein 1 (PD-1) is one of immune checkpoints which may prevent overactivated immune attack and lead to a tolerant immune microenvironment. Little is known about the involvement of PD-1-mediated immunoregulation at the maternal-fetal interface in PE. To investigate the inflammatory pattern and the involvement of PD-1 in the decidua of women with PE, decidual tissues were obtained from PE and control pregnant women. Quantitative RT-PCR analysis of the mRNA levels of the inflammatory cytokines was performed. PD-1 expression was detected by immunohistochemistry, western blot analysis, and flow cytometry. To prove the role of PD-1, decidual immune cells were incubated with blocking antibodies, and the inflammatory cytokines were detected by ELISA. We observed that the mRNA levels of IL-1β, IL-6, TNF-α, and IFN-γ were higher in the decidua of the PE group than in the decidua of the control group. The mRNA levels of IL-4 and IL-10 were lower in PE. The expression level of PD-1 was significantly downregulated, and the proportion (%) of PD-1 + CD45 + cells was significantly lower in PE. There was a significant linear correlation between PD-1 expression and common proinflammatory cytokines in the decidua. Anti-PD-1 blocking antibody significantly increased the secretion of proinflammatory cytokines. Our data suggested that the inflammatory pattern and decreased PD-1 expression in the decidua might play an active role in the local immunoregulatory mechanisms of PE. The PD-1 pathway in the maternal-fetal interface possibly function to break the tolerant immune microenvironment in PE via inflammatory cytokines.

Narrative review of the relationship between the maternal-fetal interface immune tolerance and the onset of preeclampsia.

Background and ObjectiveThe establishment of maternal-fetal interface immune tolerance is essential for successful pregnancy. Studies have shown that spontaneous abortion, recurrent abortion, and fetal growth restriction are related to maternal-fetal interface immune dysfunction. Preeclampsia is an idiopathic condition related to pregnancy which manifests as hypertension, proteinuria, and other target organ damage after 20 weeks of gestation. Although the etiology of preeclampsia is still unknown, its pathogenesis is thought to be related to genetics, environment, and metabolism. In recent years, more and more studies have been conducted on the mechanism of immune tolerance at the maternal-fetal interface and the relationship between immune dysregulation and the pathogenesis of preeclampsia. This paper summarizes the latest studies on this topic in order to find new insights into the pathogenesis of preeclampsia and make a reflection on clinical diagnosis and treatment in different phenotype of preeclampsia.MethodsThe research and latest progress published from 2000 to December 2021 on the relationship between maternal-fetal interface immune tolerance and preeclampsia were broadly retrieved and researched using PubMed and Web of Science databases.Key Content and FindingsThe mechanism of natural killer cells (NK cells) and macrophages at the maternal-fetal interface in immune tolerance, as well as their cytotoxicity and cytokine secretion dysfunction, may be related to the pathogenesis of preeclampsia. The expression of nonclassical type I human leukocyte antigen (HLA) on extravillous trophoblast (EVT) cell were down-regulated in decidua of preeclampsia, which may induce increase EVT death caused by activating of cytotoxic NK cell. In addition, genetic polymorphism of nonclassical type I HLA on the EVT cell membrane may be related to the pathogenesis of preeclampsia, although this is likely to be a combination of 3 nonclassical type I HLA genotypes and requires sequencing to verify.ConclusionsWe demonstrated how the maternal-fetal interface immune dysfunction contribute to the pathogenesis of preeclampsia, further study and clinical trial based on this theory of pathogenesis may reveal new immune treatment method of preeclampsia.

Effect of Pravastatin on Biomolecular Parameters of Preeclampsia in the Placenta of Wistar Rats

The etiology of preeclampsia consists of 2 stages, first, abnormal placentation which can increase ROS, and the inflammatory response then progresses to angiogenic imbalance. Pravastatin has a pleiotropic effect that can act as an antioxidant, anti-inflammatory, and anti-apoptotic, which is expected to be a vasodilator for angiogenic balance and reduce proinflammatory cytokines. This study aimed to examine the effect of pravastatin on the expression of angiogenic factors (sFlt-1 and VEGF) and inflammatory response (TNF-α and IL-10) in the placenta of preeclamptic rat models. This study is an experimental study, only post- test with a control group design using the placenta of preeclamptic rat models (L-NAME induced) and given pravastatin in 3 doses, namely 2 mg, 4 mg, and 8 mg.

Pre-eclampsia: a Scoping Review of Risk Factors and Suggestions for Future Research Direction.

Most of maternal deaths are preventable, and one-quarter of maternal deaths are due to pre-eclampsia and eclampsia. Prenatal screening is essential for detecting and managing pre-eclampsia. However, pre-eclampsia screening is solely based on maternal risk factors and has low (< 5% in the USA) detection rates. This review looks at pre-eclampsia from engineering, public health, and medical points of view. First, pre-eclampsia is defined clinically, and the biological basis of established risk factors is described. The multiple theories behind pre-eclampsia etiology should serve as the scientific basis behind established risk factors for pre-eclampsia; however, African American race does not have sufficient evidence as a risk factor. We then briefly describe predictive statistical models that have been created to improve screening detection rates, which use a combination of biophysical and biochemical biomarkers, as well as aspects of patient medical history as inputs. Lastly, technologies that aid in advancing pre-eclampsia screening worldwide are explored. The review concludes with suggestions for more robust pre-eclampsia research, which includes diversifying study sites, improving biomarker analytical tools, and for researchers to consider studying patients before they become pregnant to improve pre-eclampsia detection rates. Additionally, researchers must acknowledge the systemic racism involved in using race as a risk factor and include qualitative measures in study designs to capture the effects of racism on patients.Lay SummaryPre-eclampsia is a pregnancy-specific hypertensive disorder that can affect almost every organ system and complicates 2–8% of pregnancies globally. Here, we focus on the biological basis of the risk factors that have been identified for the condition. African American race currently does not have sufficient evidence as a risk factor and has been poorly studied. Current clinical methods poorly predict a patient’s likelihood of developing pre-eclampsia; thus, researchers have made statistical models that are briefly described in this review. Then, low-cost technologies that aid in advancing pre-eclampsia screening are discussed. The review ends with suggestions for research direction to improve pre-eclampsia screening in all settings.Overall, we suggest that the future of pre-eclampsia screening should aim to identify those at risk before they become pregnant. We also suggest that the clinical standard of assessing patient risk solely on patient characteristics needs to be reevaluated, that study locations of pre-eclampsia research need to be expanded beyond a few high-income countries, and that low-cost technologies should be developed to increase access to prenatal screening.

The Autophagy-Lysosomal Machinery Enhances Cytotrophoblast–Syncytiotrophoblast Fusion Process

Poor placentation is closely related with the etiology of preeclampsia and may impact fetal growth restriction. For placental developmental growth, we have demonstrated that dysregulation of autophagy, a key mechanism to maintain cellular homeostasis, in trophoblasts contributes to the pathophysiology of preeclampsia, a severe pregnancy complication, associated with poor placentation. It remains, however, unknown whether autophagy inhibition affects trophoblast syncytialization. This study evaluated the effect of autophagy in an in vitro syncytialization method using BeWo cells and primary human trophoblasts (PHT). In this study, we observed that autophagic activity decreased in PHT and BeWo cells during syncytialization. This decreased activity was accompanied by downregulation of the transcription factor, TFEB. Next, bafilomycin A1, an inhibitor of autophagy via suppressing V-ATPase in lysosomes, inhibited hCG production, CYP11A1 expression (a marker of differentiation), p21 expression (a senescence marker), and cell fusion in BeWo cells and PHT cells. Finally, LLOMe, an agent inducing lysosomal damage, also inhibited syncytialization and led to TFEB downregulation. Taken together, the autophagy-lysosomal machinery plays an important role in cytotrophoblast fusion, resulting in syncytiotrophoblasts. As autophagy inhibition contributed to the failure of differentiation in cytotrophoblasts, this may result in the poor placentation observed in preeclampsia.

Kisspeptin and Sex Steroid Hormone Receptors Are Upregulated at the Maternal‐Fetal Interface of the Preeclamptic‐like BPH/5 Mouse

The main features of preeclampsia (PE), a devastating syndrome that affects 5‐8% of pregnancies worldwide, are spontaneously recapitulated by the Blood Pressure High Subline 5 (BPH/5) mouse model. Comparable to women with early‐onset PE, BPH/5 females develop poor placentation with decreased trophoblast cell invasion, shallower placental discs and reduced placental endothelial remodelling than control C57 mice. Kisspeptins (KP), encoded by Kiss1, have been implicated in the etiology of PE: KP upregulation at the human maternal‐fetal interface is suggested to inhibit trophoblast cell invasion and angiogenesis. However, uterine KP expression pre‐pregnancy in women that later develop PE and the upstream signaling mechanisms leading to uterine/placental KP upregulation remain vastly unexplored. Interestingly, administration of estradiol‐17ß (E2) and/or progesterone (P4) to non‐pregnant ovariectomized CD‐1 mice resulted in uterine Kiss1upregulation. We have previously shown that BPH/5 females present abnormal circulating E2 and P4 throughout the estrous cycle and early pregnancy. Furthermore, KP and KP receptor (Kiss1r) are upregulated at the BPH/5 maternal‐fetal interface during the peak of decidualization, at embryonic day (e) 7.5. Therefore, the goal of this study was to investigate mRNA expression of Kiss1/Kiss1r,and the receptors for Progesterone (PR‐a/b/c)and Estrogen (ER‐αand GPER‐1)in BPH/5 non‐pregnant uterus during the first day of diestrus (NP‐D) and embryonic implantation sites (eIS) at e4.5. We hypothesized that the sex steroid hormone receptors would be upregulated in the uterus/eIS of BPH/5 during NP‐D and e4.5, respectively, potentially contributing with Kiss1/Kiss1rupregulation. Daily vaginal cytology samples were collected from adult BPH/5 and C57 females to determine the stage of the estrous cycle, and uterine samples were collected on the first day of cytologic diestrus (NP‐D, n = 3‐6/strain). Moreover, adult BPH/5 and C57 females were bred, and eIS were collected at e4.5 (n = 7‐9/strain). Gene expression was investigated using quantitative RT‐PCR and comparisons were performed using unpaired T‐tests. Welch’s corrections were performed for unequal variances and the significance level was set at α ≤ 0.05. Kiss1expression was higher in BPH/5 NP‐D uterus (p = 0.04) and e4.5 eIS (p = 0.01) when compared with C57. Contrarily, Kiss1rwas not different between BPH and C57 in NP‐D or e4.5 (p &gt; 0.05). Interestingly, PR‐a/b/cand ER‐αwere also higher in the uterus/eIS of BPH/5 females both during NP‐D (p = 0.05 and 0.02, respectively) and e4.5 (p = 0.003 and 0.02, respectively). The trans‐membrane G‐protein‐coupled estrogen receptor 1 (GPER‐1), largely associated with rapid, non‐genomic cellular responses to estrogens, was also higher in BPH/5 eIS at e4.5 when compared with controls C57 (p &lt; 0.001), but not different between groups in NP‐D (p &gt; 0.05). In conclusion, uterine Kiss1upregulation precedes pregnancy in the BPH/5 mouse model. Furthermore, PR‐a/b/cand ER‐α expression in the NP‐D uterus and early maternal fetal interface parallels the expression levels of Kiss1in the PE‐like BPH/5 mouse.

Cardiac and placental imaging (CARP) in pregnancy to assess aetiology of preeclampsia

IntroductionThe CARP study aims to investigate placental function, cardiac function and fetal growth comprehensively during pregnancy, a time of maximal cardiac stress, to work towards disentangling the complex cardiac and placental interactions presenting in the aetiology of pre-eclampsia as well as predicting maternal Cardiovascular Disease (CVD) risk in later life. BackgroundThe involvement of the cardiovascular system in pre-eclampsia, one of the most serious complications of pregnancy, is evident. While the manifestations of pre-eclampsia during pregnancy (high blood pressure, multi-organ disease, and placental dysfunction) resolve after delivery, a lifelong elevated CVD risk remains. MethodAn assessment including both cardiac and placental Magnetic Resonance Imaging (MRI) optimised for use in pregnancy and bespoke to the expected changes was developed. Simultaneous structural and functional MRI data from the placenta, the heart and the fetus were obtained in a total of 32 pregnant women (gestational ages from 18.1 to 37.5 weeks), including uncomplicated pregnancies and five cases with early onset pre-eclampsia. ResultsThe achieved comprehensive MR acquisition was able to demonstrate a phenotype associated with pre-eclampsia linking both placental and cardiac factors, reduced mean T2* (p < 0.005), increased heterogeneity (p < 0.005) and a trend towards an increase in cardiac work, larger average mass (109.4 vs 93.65 gr), wall thickness (7.0 vs 6.4 mm), blood pool volume (135.7 vs 127.48 mL) and mass to volume ratio (0.82 vs 0.75). The cardiac output in the controls was, controlling for gestational age, positively correlated with placental volume (p < 0.05). DiscussionThe CARP study constitutes the first joint assessment of functional and structural properties of the cardiac system and the placenta during pregnancy. Early indications of cardiac remodelling in pre-eclampsia were demonstrated paving the way for larger studies.

Analytical validation of a novel panel of biomarkers for a test for preeclampsia

Preeclampsia is a serious condition responsible for much pregnancy-related morbidity and mortality. Diagnosis of preeclampsia is difficult due to the non-specific and subjective nature of symptoms of the disease. To reduce the subjective decision making and management of preeclampsia, we identified a panel of biomarkers representing multiple and different pathogenic pathways implicated in the etiology of preeclampsia, and developed a test referred to as Preecludia™. An algorithm based on eight biomarkers (cluster of differentiation 274 (CD274), decorin, endoglin, fibroblast growth factor-21 (FGF21), soluble fms-related tyrosine kinase 1 (sFlt-1), kidney injury molecule-1 (KIM-1), free placental growth factor (PlGF), and total PlGF) and gestational age at the time of sample collection was constructed to rule out preeclampsia in women presenting with signs and symptoms of preeclampsia. The analytical performance of each of the individual biomarker assays that comprise the Preecludia™ test was evaluated. Herein we report the test’s precision, analytical range, analytical sensitivity, parallelism, linearity, interference, analytical specificity, analytical accuracy, and stability. The data indicate that these biomarker assays exhibit a high level of inter-run precision of less than 15%, with minimal interference.

Vitamin D receptor gene polymorphism in Madura pregnant women with hypertension: a case control study

BackgroundGenetic factors are important considerations in the etiology of preeclampsia and gestational hypertension. Several previous studies have shown an association of Vitamin D receptor (VDR) gene polymorphisms with hypertension in pregnancy. However, the number of studies is still very limited and the results differ from one another.Aim of the studyThis study aimed to analyze the polymorphisms of rs2228570 and rs731236 of the VDR gene in subjects with hypertension and non-hypertension in pregnancy in Madura ethnicity.Subjects and methodsThe researchers conducted tests for two polymorphisms in the VDR gene among 210 subjects consisting of 105 pregnant women with hypertension and 105 non-hypertension pregnant women from Madura ethnicity. The rs2228570 (T>C) and rs731236 (C>T) polymorphisms were detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. All data were analyzed by T-tests and Chi-Square tests.ResultsThe TT genotype frequency of rs2228570 (15.2%) in the hypertension group was higher than in the control group (6.7%) (p = 0.047). Subjects with the TT genotype at rs2228570 showed a 3.048 times greater risk of developing hypertension than the CC genotype (OR = 3.048: 1.135–8.183, p = 0.023). The T allele frequency of rs2228570 (40.5%) in the hypertension group was higher than in the control group (30.5%) (p = 0.032). Subjects with the T allele had 1.551 times greater risk of developing hypertension. There was no significant difference in genotype and allele of rs731236 between hypertension subjects and controls.ConclusionThe TT genotype and T allele of rs2228570 in the hypertension group were risk factors for hypertension in this study. While the TT genotype and T allele at rs731236 were not risk factors for hypertension in pregnancy. Genotyping of VDR gene polymorphisms in pregnant women is expected to be useful in strategies for treating hypertension in pregnancy.

A Review of Roles of Uterine Artery Doppler in Pregnancy Complications

The invasion of trophoblasts into the uterine decidua and decidual vessels is critical for the formation of placenta. The defects of placentation are related to the etiologies of preeclampsia (PE), fetal growth restriction (FGR), and small-for-gestational age (SGA) neonates. It is possible to predict significant vascular events during pregnancy through uterine artery Doppler (UAD). From the implantation stage to the end of pregnancy, detecting changes in uterine and placental blood vessels can provide a favorable diagnostic instrument for pregnancy complications. This review aims to collect literature about the roles of UAD in pregnancy complications. We consider all relevant articles in English from January 1, 1983 to October 30, 2021. Predicting pregnancy complications in advance allows practitioners to carry out timely interventions to avoid or lessen the harm to mothers and neonates. Administering low-dose aspirin daily before 16 weeks of pregnancy can significantly reduce the incidence of pregnancy complications. From early pregnancy to late pregnancy, UAD can combine with other maternal factors, biochemical indicators, and fetal measurement data to identify high-risk population. The identification of high-risk groups can also lessen maternal mortality. Besides, through moderate risk stratification, stringent monitoring for high-risk pregnant women can be implemented, decreasing the incidence of adversities.

TAGLN2-Regulated Trophoblast Migration, Invasion and Fusion are Impaired in Preeclampsia.

Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year and is closely related to abnormal trophoblast function. However, research on placental trophoblast functional abnormalities is insufficient, and the etiology of PE is unclear. Here, we report that the expression of transgelin-2 (TAGLN2) was downregulated in the placenta of patients with PE. In addition, a lack of TAGLN2 significantly reduced the ability of trophoblasts to migrate, invade and fuse. A co-immunoprecipitation (Co-IP) and microscale thermophoresis analysis showed that TAGLN2 bound directly to E-cadherin. A decrease in TAGLN2 expression led to a reduction in cleavage of the E-cadherin extracellular domain, thereby regulating the function of trophoblasts. In addition, we found that a reduction in soluble E-cadherin may also have an effect on blood vessel formation in the placenta, which is necessary for normal placental development. What’s more, the in vivo mouse model provided additional evidence of TAGLN2 involvement in the development of PE. By injecting pregnant mice with Ad-TAGLN2, we successfully generated a human PE-like syndrome that resulted in high blood pressure and some adverse pregnancy outcomes. Overall, the association between TAGLN2 and PE gives a new insight into PE diagnosis and treatment.

Calcemia, Vitamin D and seasonal influences in preeclampsia in Goma

Background: The etiology of preeclampsia remains less well known. It is noted that low vitamin D levels are associated with a high risk of preeclampsia (PE). Calcium (Ca2+) levels during pregnancy appear to be involved in pregnancy-induced hypertension. Recent studies indicate that serum calcium levels may have a role in preeclampsia. Vitamin D promotes absorption of proper concentration of calcium in the blood which helps to lower blood pressure. The complications associated with calcium deficiency during a normal pregnancy are numerous and have not been extensively studied in Goma. Objective: To assess blood calcium levels (ionic and total) in preeclamptic women and to analyse the seasonal influence on preeclampsia in Goma. Method: A prospective case-control study (without matching) of 190 pregnant women without cardiovascular or endocrine diseases for a case-control ratio of 1∶1 was conducted in six hospitals in Goma. Blood ionogram was performed by an automated system directly after blood sampling and vitamin D was measured using enzyme-linked immunosorbent method. Results: The mean ionised calcium level in preeclamptic woman was 1.24±0.16 mmol/L (0.48-1.59) compared to 1.27±0.17 mmol/L (0.88-2.30) in normal pregnant woman (p=0.214). A slight negative correlation between blood calcium and blood pressure was observed in pregnant women. Low vitamin D levels were associated with preeclampsia. Hypovitaminosis D in the preeclamptic group was more observed during the rainy season than during the dry season. Pregnancies complicated by PE were from fertilisations occurring during the rainy season while the dry season was characterised by a high admission of preeclamptics. Conclusion: The study found that preeclamptic women in Goma had hypocalcemia. There was also a weak negative correlation between blood pressure and serum calcium levels. The majority of preeclamptics were diagnosed during the dry season, while conception with a PE complication occurred during the rainy season. As this is a first study in this area for the Great Lakes region of Africa, a more in-depth study with a larger sample size is desired.

Preeclampsia at delivery is associated with lower serum vitamin D and higher antiangiogenic factors: a case control study

BackgroundPreeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Vitamin D plays an important role in pregnancy influencing implantation, angiogenesis and placental development. The objective of this study was to determine whether there is an association between serum vitamin D levels, and anti-angiogenic factors at the time of delivery and the occurrence of preeclampsia.MethodsThis nested case control study analyzed frozen serum samples at the time of delivery and related clinical data from women with singleton liveborn pregnancies who had participated in studies of the NICHD Stillbirth Collaborative Research Network. Women with a recorded finding of preeclampsia and who had received magnesium sulfate treatment prior to delivery were considered index cases (N = 56). Women without a finding of preeclampsia were controls (N = 341).ResultsWomen with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher sFlt-1 levels (11,600 pg/ml vs. 7050 pg/ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001). After controlling for gestational age at delivery and maternal BMI, vitamin D levels were 0.88 times lower (P = 0.051), while endoglin levels were 2.5 times higher and sFlt-1 levels were 2.1 times higher than in control pregnancies (P < 0.001).ConclusionsWomen with preeclampsia at time of delivery have higher maternal antiangiogenetic factors and may have lower maternal serum vitamin D levels. These findings may lead to a better understanding of the underlying etiology of preeclampsia as well as possible modifiable treatment options which could include assuring adequate levels of maternal serum vitamin D prior to pregnancy.

Placental mRNA and Protein Expression of VDR, CYP27B1 and CYP2R1 Genes Related to Vitamin D Metabolism in Preeclamptic Women

(1) Background: Considerable evidence indicates that the occurrence of preeclampsia (PE) is associated with a reduced vitamin D (VD) level. Several studies have found that VD deficiency is correlated with disturbed trophoblast invasion, reduced angiogenesis and increased vasoconstriction. Because the vitamin D receptor (VDR) and CYP27B1 and CYP2R1 hydrolases are strongly involved in VD metabolism, the goal of the present study was to evaluate their genes and proteins expression in the placentas from preeclamptic women. (2) Methods: Samples and clinical data were obtained from 100 Polish women (41 women with preeclampsia and 59 healthy pregnant controls). The whole PE group was divided into subgroups according to gestation week of pregnancy ending before and after 34 gestational weeks (early/late-onset preeclampsia (EOPE/LOPE)). However, finally, to reduce confounding by differences in gestational age, the EOPE group was excluded from the analysis of mRNA and protein placental expression, and we focus on the comparison between LOPE and control groups. The placental VDR, CYP27B1 and CYP2R1 mRNA expression was analyzed using RT-PCR, and placental protein levels were determined by ELISA assay. (3) Results. (3.1) Placental gene expression: Expression levels of both genes, CYP27B1 (1.17 vs. 1.05 in controls, p = 0.006) and CYP2R1 (2.01 vs. 1.89 in controls, p = 0.039), were significantly higher in preeclamptic placentas than in the control group. Interestingly, VDR expression was significantly lower in placentas from the PE group (1.15 vs. 1.20 in controls, p = 0.030). After dividing all preeclamptic women into subgroups only for the CYP27B1 gene, a significantly higher placental expression in the LOPE subgroup than the healthy controls was observed (padj = 0.038). (3.2) Placental protein expression: The results revealed that protein expression levels of CYP27B1 in the preeclamptic group were similar (5.32 vs. 5.23 in controls, p = 0.530). There was a significant difference in median VDR and CYP2R1 protein levels between studied groups (VDR: 2.56 vs. 3.32 in controls, p &lt; 0.001; CYP2R1: 1.32 vs. 1.43 in controls, p = 0.019). After stratification of preeclamptic women into subgroups, a significant difference was observed only in the VDR protein level. The medians in the LOPE subgroups were significantly lower compared to the healthy control group. In the whole study group, the placental VDR protein level was inversely correlated with systolic and diastolic blood pressure (all p &lt; 0.001), and positively correlated with gestational age (p &lt; 0.001) and infant birth weight (p = 0.014). (4) Conclusions: Lower mRNA and protein expression of VDR in preeclamptic placentas, and also VDR protein expression, could play a pivotal role in preeclampsia development. Additionally, the higher mRNA expression of both CYP27B1 and CYP2R1 hydrolase genes in placentas from preeclamptic women could indicate the compensatory role of these enzymes in preeclampsia etiology. Our results also indicate that placental VDR protein level could be one of the factors modulating blood pressure in pregnant women, as well as influencing gestational age and infant birth weight. Considering the importance of these findings, future studies are warranted.

Predicting preeclampsia and related risk factors using data mining approaches: A cross-sectional study.

BackgroundPreeclampsia is a type of pregnancy hypertension disorder that has adverse effects on both the mother and the fetus. Despite recent advances in the etiology of preeclampsia, no adequate clinical screening tests have been identified to diagnose the disorder.ObjectiveWe aimed to provide a model based on data mining approaches that can be used as a screening tool to identify patients with this syndrome and also to identify the risk factors associated with it.Materials and MethodsThe data used to perform this cross-sectional study were extracted from the clinical records of 726 mothers with preeclampsia and 726 mothers without preeclampsia who were referred to Fatemieh Hospital in Hamadan City during April 2005–March 2015. In this study, six data mining methods were adopted, including logistic regression, k-nearest neighborhood, C5.0 decision tree, discriminant analysis, random forest, and support vector machine, and their performance was compared using the criteria of accuracy, sensitivity, and specificity.ResultsUnderlying condition, age, pregnancy season and the number of pregnancies were the most important risk factors for diagnosing preeclampsia. The accuracy of the models were as follows: logistic regression (0.713), k-nearest neighborhood (0.742), C5.0 decision tree (0.788), discriminant analysis (0.687), random forest (0.758) and support vector machine (0.791).ConclusionAmong the data mining methods employed in this study, support vector machine was the most accurate in predicting preeclampsia. Therefore, this model can be considered as a screening tool to diagnose this disorder.

Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia.

Preeclampsia (PE) is a dangerous hypertensive disorder that occurs during pregnancy. The specific aetiology and pathogenesis of PE have yet to be clarified. To better reveal the specific pathogenesis of PE, we characterized the proteome and acetyl proteome (acetylome) profile of placental tissue from PE and normal‐term pregnancy by label‐free quantification proteomics technology and PRM analysis. In this research, 373 differentially expressed proteins (DEPs) were identified by proteome analysis. Functional enrichment analysis revealed significant enrichment of DEPs related to angiogenesis and the immune system. COL12A1, C4BPA and F13A1 may be potential biomarkers for PE diagnosis and new therapeutic targets. Additionally, 700 Kac sites were identified on 585 differentially acetylated proteins (DAPs) by acetylome analyses. These DAPs may participate in the occurrence and development of PE by affecting the complement and coagulation cascades pathway, which may have important implications for better understand the pathogenesis of PE. In conclusion, this study systematically analysed the reveals critical features of placental proteins in pregnant women with PE, providing a resource for exploring the contribution of lysine acetylation modification to PE.

Epigenetic processes during preeclampsia and effects on fetal development and chronic health.

Preeclampsia (PE), the leading cause of maternal and fetal morbidity and mortality, is associated with poor fetal growth, intrauterine growth restriction (IUGR) and low birth weight (LBW). Offspring of women who had PE are at increased risk for cardiovascular (CV) disease later in life. However, the exact etiology of PE is unknown. Moreover, there are no effective interventions to treat PE or alleviate IUGR and the developmental origins of chronic disease in the offspring. The placenta is critical to fetal growth and development. Epigenetic regulatory processes such as histone modifications, microRNAs and DNA methylation play an important role in placental development including contributions to the regulation of trophoblast invasion and remodeling of the spiral arteries. Epigenetic processes that lead to changes in placental gene expression in PE mediate downstream effects that contribute to the development of placenta dysfunction, a critical mediator in the onset of PE, impaired fetal growth and IUGR. Therefore, this review will focus on epigenetic processes that contribute to the pathogenesis of PE and IUGR. Understanding the epigenetic mechanisms that contribute to normal placental development and the initiating events in PE may lead to novel therapeutic targets in PE that improve fetal growth and mitigate increased CV risk in the offspring.