Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.
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SUBMITTER: Garrido-Gomez T
PROVIDER: S-EPMC5374356 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
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Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.
Garrido-Gomez Tamara T Ona Katherine K Kapidzic Mirhan M Gormley Matthew M Simón Carlos C Genbacev Olga O Fisher Susan J SJ
Development (Cambridge, England) 20170301 5
Pre-eclampsia (PE), which affects ∼8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs nor ...[more]
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Project description:Preeclampsia (PE), which affects ~8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally up regulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g., placental proteins, markers of oxidative stress). We confirmed a sPE-related increase in production of PAPPA1, which releases IGF-1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs (schCTB), a possible explanation for expansion of this layer, which may partially compensate for the placental deficits.
2016-12-10 | GSE91189 | GEO
Project description:BackgroundAn evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases.MethodsA further analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers.ResultsThe median number of severe PE/E cases in the past year was just 5 (range 0-42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at regional and specialized hospitals (p < 0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There was a significant difference between doctors and midwives on only one item: continued use of anti-hypertensives after convulsions are controlled.ConclusionsDrugs and supplies needed to treat severe PE/E are widely available at EmONC facilities in Afghanistan, but providers lack knowledge in some areas, especially concerning the use of MgSO4 and diazepam. Providers who have specialized training or work at larger facilities are better at managing cases of severe PE/E. The findings suggest a need to clarify service delivery guidelines, offer refresher training, and reinforce best practices with supervision and reinforcement.
| S-EPMC3852136 | biostudies-literature
Project description:BackgroundPre-eclampsia with severe features (PEC) is a pregnancy-specific syndrome characterized by severe hypertension and end-organ dysfunction, and is associated with short-term adverse cardiovascular events, including heart failure, pulmonary edema, and stroke.ObjectivesThe authors aimed to characterize the short-term echocardiographic, clinical, and laboratory changes in women with PEC, focusing on right ventricular (RV) systolic pressure (RVSP) and echocardiographic-derived diastolic, systolic, and speckle tracking parameters.MethodsIn this prospective observational study, the authors recruited 63 women with PEC and 36 pregnant control patients.ResultsThe PEC cohort had higher RVSP (31.0 ± 7.9 mm Hg vs. 22.5 ± 6.1 mm Hg; p < 0.001) and decreased global RV longitudinal systolic strain (RVLSS) (-19.6 ± 3.2% vs. -23.8 ± 2.9% [p < 0.0001]) when compared with the control cohort. For left-sided cardiac parameters, there were differences (p < 0.001) in mitral septal e' velocity (9.6 ± 2.4 cm/s vs. 11.6 ± 1.9 cm/s), septal E/e' ratio (10.8 ± 2.8 vs. 7.4 ± 1.6), left atrial area size (20.1 ± 3.8 cm2 vs. 17.3 ± 2.9 cm2), and posterior and septal wall thickness (median [interquartile range]: 1.0 cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8 cm [0.7 to 0.9 cm]). Eight women (12.7%) with PEC had grade II diastolic dysfunction, and 6 women (9.5%) had peripartum pulmonary edema.ConclusionsWomen with PEC have higher RVSP, higher rates of abnormal diastolic function, decreased global RVLSS, increased left-sided chamber remodeling, and higher rates of peripartum pulmonary edema, when compared with healthy pregnant women.
| S-EPMC8136241 | biostudies-literature
Project description:The etiology of preeclampsia, a hypertensive disorder of human pregnancy, remains unknown. We addressed fetal sex selection and the suggestive role of fetal HLA-G and related genes, regulating maternal immune responses, in preeclampsia pathogenesis. We assessed birth sex ratios, weights, and seasonality of preeclampsia among 1.79 million births in Finland. We studied haplotypes of HLA-G 3’ untranslated region (UTR), regulating HLA-G expression, in 1000 Genomes series and in a preeclampsia cohort (n=1249). We quantified placental (n=163) mRNA expression of 136 genes, studied HLA-G and IFNα protein expression by immunohistochemistry, and measured maternal and fetal circulating IFNα levels by ELISA. Population-level data showed loss of male fetuses as a characteristic of preeclampsia. As a potential contributor to immune-mediated loss, we found balancing selection at HLA-G 3’UTR modulating sex ratio, and association of HLA-G 3’UTR haplotypes with placental HLA-G expression. HLA-G and its receptors were downregulated in preeclampsia placentas, and surprisingly, interferon alpha-1 (IFNA1) was highly upregulated. IFNA1 and HLA-G distinguished preeclampsia better than placental FLT1 expression. Fetal but not maternal circulating IFNα, produced by trophoblasts, showed association with maternal hypertension and fetal growth restriction. We uncover the link between placental HLA-G expression and human birth sex ratio. We propose that preeclampsia shares, through reduced HLA-G mediated immunotolerance, the mechanism needed to fight placental viral infections and malaria in evolution. IFNα upregulation in preeclampsia placenta, together with its known actions upstream of inflammatory genes, encourages testing IFNα inhibitors and especially the pregnancy-approved antimalarial hydroxichloroquine in treatment of preeclampsia.
2019-11-25 | GSE125460 | GEO
Project description:We investigated the extent to which pre-pregnancy obesity mediates the association between maternal place of birth and severe pre-eclampsia in the PreCARE cohort of pregnant women in Paris (n = 9,579). Adjusted path analysis logistic regression models were used to assess the role of pre-pregnancy obesity as a mediator in the association between maternal place of birth and the development of severe pre-eclampsia. We calculated 1. adjusted odds ratios and 95% confidence intervals for the total exposure-outcome association and for the direct and indirect/obesity-mediated components 2. the indirect/obesity-mediated effect. Ninety-five (0.99%) women developed severe pre-eclampsia, 47.6% were non-European immigrants, 16.3% were born in Sub-Saharan Africa, and 12.6% were obese (BMI > = 30 kg/m2). Women experiencing severe pre-eclampsia were more likely to be from Sub-Saharan Africa (p = 0.023) and be obese (p = 0.048). Mothers from Sub-Saharan Africa had an increased risk of severe pre-eclampsia compared to European-born mothers (aOR 2.53, 95% CI 1.39-4.58) and the obesity-mediated indirect effect was 18% of the total risk (aOR 1.18, 95%CI 1.03-1.35). In conclusion, Sub-Saharan African immigrant women have a two-fold higher risk of developing severe pre-eclampsia as compared to European-born women, one-fifth of which is mediated by pre-pregnancy obesity. Our results quantify the potential benefit of decreasing obesity among at-risk women.
| S-EPMC7089990 | biostudies-literature
Project description:BackgroundPre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point.ResultsThe use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia].ConclusionsFor pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks.
| S-EPMC4407242 | biostudies-literature
Project description:To determine differential expression of microRNAs in placentae with severe pre-eclampsia and normal placenta. Differential expression of microRNAs in placentae (4 severe pre-eclampsia and 4 normal control) was screened by microarray platform, then some differential microRNAs were selected and validated with real-time quantitative reverse transcription polymerase chain reaction in placentae of severe pre-eclampsia (n=24) and normal control group (n=26). Results: We validated the expression of some microRNAs altered in the microarray, and found the following microRNAs were significantly increased in severe pre-eclampsia placentae: miR-16, miR-29b, miR-195, miR-26b, miR-181a, miR-335 and miR-222. Conclusion: These differential microRNAs may play an important role in pathogenesis of pre-eclampsia.
2011-04-14 | GSE15789 | GEO
Project description:Introduction:Pre-eclampsia is a hypertensive disorder in pregnancy. Maternal sequelae that may occur include impaired liver function, disseminated intravascular coagulation, seizures (eclampsia), stroke, and death. Thus, providers should know how to recognize (diagnose) and treat pre-eclampsia and eclampsia. Methods:A simulator with noninvasive blood pressure monitoring was used. Transducers for fetal heart rate and contraction monitoring were placed on the simulator, which represented the patient. After obtaining a history and performing a physical examination, resident physician (postgraduate years 1-4) and nurse learners had to diagnose pre-eclampsia and treat this condition. They also had to treat severe-range blood pressures and manage eclampsia. Learner performance was assessed with a checklist. Debriefing followed the simulation. Results:Thirty resident learners participated in the study. Nurses did not participate. All resident learners indicated familiarity with the diagnosis and management of pre-eclampsia and emergent hypertension and managed these conditions correctly. All resident learners reported not being confident in managing eclampsia. None of the learners were able to stop the eclamptic seizure. All resident learners were more confident in managing eclampsia after the scenario compared with before (mean confidence level 3.6 ± 0.5 vs. 1.1 ± 0.4, p < .001). Discussion:Resident learners were familiar with the management of pre-eclampsia and emergent hypertension but not with eclampsia. We recommend that eclampsia simulations occur in a laboratory and in situ on the labor and delivery floor with interprofessional team members including obstetricians, nurses, anesthesiologists, emergency and family medicine physicians, nurse practitioners, and physician assistants.
| S-EPMC6868499 | biostudies-literature
Project description:ObjectivesTo investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19.DesignA prospective, observational study.SettingTertiary referral hospital.ParticipantsSingleton pregnancies with COVID-19 at >20+0 weeks.MethodsForty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE.Main outcome measuresIncidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF.ResultsThirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome.ConclusionsPregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution.Tweetable abstractThis study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.
| S-EPMC7300912 | biostudies-literature