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Frontiers in Genetics 2024Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the...
BACKGROUND
Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the molecular mechanism of macrophages in pre-eclampsia is not well understood.
METHODS
In this study, the key biomarkers during the development of pre-eclampsia were identified using bioinformatics analysis. The GSE75010 and GSE74341 datasets from the GEO database were obtained and merged for differential analysis. A weighted gene co-expression network analysis (WGCNA) was constructed based on macrophage content, and machine learning methods were employed to identify key genes. Immunoinfiltration analysis completed by the CIBERSORT method, R package "ClusterProfiler" to explore functional enrichment of these intersection genes, and potential drug predictions were conducted using the CMap database. Lastly, independent analysis of protein levels, localization, and quantitative analysis was performed on placental tissues collected from both preeclampsia patients and healthy control groups.
RESULTS
We identified 70 differentially expressed NETs genes and found 367 macrophage-related genes through WGCNA analysis. Machine learning identified three key genes: FNBP1L, NMUR1, and PP14571. These three key genes were significantly associated with immune cell content and enriched in multiple signaling pathways. Specifically, these genes were upregulated in PE patients. These findings establish the expression patterns of three key genes associated with M2 macrophage infiltration, providing potential targets for understanding the pathogenesis and treatment of PE. Additionally, CMap results suggested four potential drugs, including Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin, which may have the potential to reverse pre-eclampsia.
CONCLUSION
Studying the expression levels of three key genes in pre-eclampsia provides valuable insights into the prevention and treatment of this condition. We propose that these genes play a crucial role in regulating the maternal-fetal immune microenvironment in PE patients, and the pathways associated with these genes offer potential avenues for exploring the molecular mechanisms underlying preeclampsia and identifying therapeutic targets. Additionally, by utilizing the Connectivity Map database, we identified drug targets like Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin as potential clinical treatments for preeclampsia.
PubMed: 38846957
DOI: 10.3389/fgene.2024.1376971 -
Annals of Medicine and Surgery (2012) Jun 2024Pre-eclampsia and eclampsia are medical conditions that can cause severe complications, such as maternal and foetal morbidity and mortality. This study aimed to assess...
The silent threat: investigating the incidence and clinical characteristics of pre-eclampsia and eclampsia in women from tertiary care hospitals of the Democratic Republic of Congo.
BACKGROUND
Pre-eclampsia and eclampsia are medical conditions that can cause severe complications, such as maternal and foetal morbidity and mortality. This study aimed to assess the incidence and characteristics of pre-eclampsia and eclampsia.
METHODS
From July 2021 to July 2022, the authors conducted a retrospective, cross-sectional, descriptive study in the Department of Obstetrics and Gynaecology of a tertiary care hospital in the Democratic Republic of the Congo (DR Congo). Out of 1236 total deliveries, 40 patients aged 18-35 years with pre-eclampsia and/or eclampsia with complete data in medical records were studied.
RESULTS
In the studied group, 3.23% of women (40 cases) experienced pre-eclampsia or eclampsia, with the majority (75%, 30 cases) occurring before childbirth. Among these, 62.5% (25 cases) were first-time mothers. The main complications observed in the mothers included HELLP syndrome and placental abruption, whereas their newborns frequently exhibited delayed in-utero growth. Caesarean delivery was the prevalent birthing method, and the treatments most often used for effective management were magnesium sulfate and nicardipine.
CONCLUSION
The research highlights the common occurrence of eclampsia among patients in the DRC and stresses the critical need for prompt detection of hypertensive complications during pregnancy, aiming to reduce negative health impacts on both mothers and their children.
PubMed: 38846848
DOI: 10.1097/MS9.0000000000002087 -
Frontiers in Endocrinology 2024Leptin and its receptors are expressed by the human placenta throughout gestation, yet the role of leptin in early human placental development is not well characterized....
INTRODUCTION
Leptin and its receptors are expressed by the human placenta throughout gestation, yet the role of leptin in early human placental development is not well characterized. Leptin is overexpressed in the placentas from preeclamptic (PE) pregnancies. PE can result from the impaired invasion of fetal placental cells, cytotrophoblasts (CTBs), into the maternal decidua. We hypothesized that elevated leptin levels would impair human CTB invasion.
METHODS
The effects of leptin on the invasion of human CTBs were evaluated in three cell models, HTR-8/SVneo cells, primary CTBs, and placental villous explants using invasion assays. Further, leptin receptor expression was characterized in all three cell models using RT-PCR. Further phosphokinase assays were performed in HTR-8/SVneo cells to determine signaling pathways involved in CTB invasion in response to differential leptin doses.
RESULTS
We found that, prior to 8 weeks gestation, leptin promoted CTB invasion in the explant model. After 11 weeks gestation in explants, primary CTBs and in HTR-8/SVneo cells, leptin promoted invasion at moderate but not at high concentrations. Further, leptin receptor characterization revealed that leptin receptor expression did not vary over gestation, however, STAT, PI3K and MAPK pathways showed different signaling in response to varied leptin doses.
DISCUSSION
These data suggest that the excess placental leptin observed in PE may cause impaired CTB invasion as a second-trimester defect. Leptin's differential effect on trophoblast invasion may explain the role of hyperleptinemia in preeclampsia pathogenesis.
Topics: Humans; Trophoblasts; Leptin; Female; Pregnancy; Gestational Age; Receptors, Leptin; Placenta; Pre-Eclampsia; Dose-Response Relationship, Drug; Signal Transduction; Placentation; Cell Movement
PubMed: 38846494
DOI: 10.3389/fendo.2024.1386309 -
Medical Science Monitor : International... Jun 2024BACKGROUND Severe pre-eclampsia (sPE) and postpartum hemorrhage (PPH) in pregnancy have serious impact on maternal and fetal health and life. Co-occurrence of sPE and...
BACKGROUND Severe pre-eclampsia (sPE) and postpartum hemorrhage (PPH) in pregnancy have serious impact on maternal and fetal health and life. Co-occurrence of sPE and PPH often leads to poor pregnancy outcomes. We explored risk factors associated with PPH in women with sPE. MATERIAL AND METHODS This retrospective study included 1953 women with sPE who delivered at the Women's Hospital of Nanjing Medical University between April 2015 and April 2023. Risk factors for developing PPH in sPE were analyzed, and subgroups were analyzed by delivery mode (cesarean and vaginal). RESULTS A total of 197 women with PPH and 1756 women without PPH were included. Binary logistic regression results showed twin pregnancy (P<0.001), placenta accreta spectrum disorders (P=0.045), and placenta previa (P<0.001) were independent risk factors for PPH in women with sPE. Subgroup analysis showed risk factors for PPH in cesarean delivery group were the same as in the total population, but vaginal delivery did not reduce risk of PPH. Spinal anesthesia reduced risk of PPH relative to general anesthesia (P=0.034). Vaginal delivery group had no independent risk factors for PPH; however, magnesium sulfate (P=0.041) reduced PPH incidence. CONCLUSIONS Women with twin pregnancy, placenta accreta spectrum disorders, placenta previa, and assisted reproduction with sPE should be alerted to the risk of PPH, and spinal anesthesia should be preferred in cesarean delivery. Magnesium sulfate should be used aggressively in women with sPE; however, the relationship between magnesium sulfate and PPH risk needs further investigation.
Topics: Humans; Female; Pregnancy; Risk Factors; Postpartum Hemorrhage; Retrospective Studies; Adult; Pre-Eclampsia; Cesarean Section; China; Placenta Previa; Delivery, Obstetric; Pregnancy, Twin; Placenta Accreta; Pregnancy Outcome; Logistic Models; Incidence
PubMed: 38845159
DOI: 10.12659/MSM.943772 -
Nigerian Journal of Clinical Practice May 2024Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in...
BACKGROUND AND AIM
Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia.
MATERIALS AND METHODS
A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters.
RESULTS
Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively).
CONCLUSION
These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.
Topics: Humans; Female; Pregnancy; Adult; Pre-Eclampsia; Case-Control Studies; Hypertension, Pregnancy-Induced; Blood Coagulation; Severity of Illness Index; Young Adult; Fibrinogen; Prothrombin Time; Mean Platelet Volume; Hemoglobins; Partial Thromboplastin Time
PubMed: 38842709
DOI: 10.4103/njcp.njcp_645_23 -
BMC Women's Health Jun 2024A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to...
Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study.
BACKGROUND
A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20 weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO).
METHODS
We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups.
RESULTS
The gravidity and parity in the elevated free β-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free β-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free β-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001).
CONCLUSIONS
APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free β-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free β-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free β-hCG level and the occurrence of APO.
Topics: Humans; Pregnancy; Female; Retrospective Studies; Pregnancy Trimester, Second; Adult; Pregnancy Outcome; Chorionic Gonadotropin, beta Subunit, Human; Pregnancy Complications; China; Pre-Eclampsia; Cohort Studies; Polyhydramnios; Chorionic Gonadotropin; Hyperlipidemias
PubMed: 38835013
DOI: 10.1186/s12905-024-03105-z -
PloS One 2024Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid, particularly glycine conjugate, may compromise blood flow and cause functional hypoxia-ischemia.
AIMS
This meta-analysis aims to assess the association between ICP and key pregnancy outcomes including emergency caesarian sections (C-sections), preeclampsia, hemorrhage, preterm birth, small for gestational age, admission rate to neonatal intensive care union (NICU), gestational age, and stillbirth.
MATERIALS AND METHODS
Literature search across five databases (PubMed, Embase, Web of Science) was done to detect relevant studies published up until June 2023. Meta-analysis of the identified studies was done using a random-effects model, and the results presented as Odds ratio (OR).
RESULTS
A literature search identified 662 studies. Of them, 21 met the inclusion criteria. There was a significant association between ICP and odds of C-section (OR: 1.42, p <0.001), preeclampsia (OR: 2.64, p <0.001), NICU admission (OR: 2.1, p <0.001), and pre-term birth (OR: 2.64, p <0.001). ICP was not associated with postpartum hemmorhage (OR: 1.31, p = 0.13), small for gestational age (OR: 0.87, p = 0.07), stillbirth (OR: 1.49, p = 0.29).
CONCLUSIONS
Our results confirm the adverse effects of ICP on co-existing pregnancy complications, obstetric and neonatal outcomes. ICP in associated with severe complications including increased rates of preeclampsia, emergency C-sections, preterm births, l gestational periods and higher rates of NICU admissions. These results may assist healthcare professionals in formulating comprehensive care guidelines for expectant mothers and newborns.
Topics: Humans; Pregnancy; Cholestasis, Intrahepatic; Female; Pregnancy Complications; Infant, Newborn; Pregnancy Outcome; Premature Birth; Stillbirth; Pre-Eclampsia; Cesarean Section; Gestational Age; Infant, Small for Gestational Age
PubMed: 38833446
DOI: 10.1371/journal.pone.0304604 -
Scientific Reports Jun 2024Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness...
Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (< 2.36 mg/mg) and high PCR group (≥ 2.36 mg/mg). Ophthalmologic clinical data were collected and assessed. We observed higher antepartum CT and higher mean arterial pressure in high PCR group than in low PCR group. Moreover, postpartum CT decreased significantly in high PCR group. In the multivariate analysis, CT changes were correlated with antepartum CT and antepartum PCR after logarithm transformation. In conclusion, a greater decrease in CT was observed in high PCR group than in low PCR group. Further, the antepartum PCR showed a correlation with the extent of CT reduction.
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Proteinuria; Adult; Choroid; Postpartum Period; Retrospective Studies; Creatinine
PubMed: 38830948
DOI: 10.1038/s41598-024-63359-3 -
Cellular and Molecular Life Sciences :... May 2024The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are...
The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the differentiation of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSCs) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups, suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions.
Topics: Trophoblasts; Female; Pregnancy; Cell Differentiation; Animals; Humans; Mice; Placentation; Glycosylphosphatidylinositols; Placenta; Wnt Signaling Pathway; Pre-Eclampsia; Endoplasmic Reticulum; Biosynthetic Pathways; Unfolded Protein Response; CRISPR-Cas Systems
PubMed: 38819479
DOI: 10.1007/s00018-024-05284-2 -
Cureus Apr 2024Introduction Pre-eclampsia leads to long-lasting cardiovascular effects in women in the postpartum period, but prevalence and in-hospital adverse events of coronary...
Introduction Pre-eclampsia leads to long-lasting cardiovascular effects in women in the postpartum period, but prevalence and in-hospital adverse events of coronary artery disease (CAD) in women with pre-eclampsia are poorly understood. The prevalence, outcomes, and mortality risks identified in this study allow for possible routes of clinical intervention of CAD in women with pre-eclampsia. The purpose of this study was to determine the prevalence and outcomes of CAD in women diagnosed with pre-eclampsia compared to those with pre-eclampsia with no history of CAD. Predictors of mortality in pre-eclampsia were also analyzed. Methods Data were obtained from the National Inpatient Sample from January 2016 to December 2019. We used the multivariate logistic regression to assess the independent association of CAD with outcomes in patients admitted with pre-eclampsia. We also used the multivariate logistic regression to analyze predictors of mortality in patients hospitalized with pre-eclampsia. Results Women with pre-eclampsia admitted between January 2016 and December 2019 were included in our analysis. A total of 256,010 patients were diagnosed with pre-eclampsia. Of these patients, 174 (0.1%) patients had CAD. Multivariate analysis demonstrated that CAD in patients with pre-eclampsia was independently associated with angioplasty (adjusted odds ratio [aOR] 62.28; 95% CI 20.459-189.591; p=0.001), permanent pacemaker (aOR 35.129; 95% CI 13.821-89.287; p=0.001), left heart catheterization (aOR 29.416; 95% CI 7.236-119.557; p=0.001), non-ST-elevation myocardial infarction (NSTEMI) (aOR 25.832; 95% CI 7.653-87.189; p=0.001), and congestive heart failure (CHF) (aOR 13.948; 95% CI 7.648-25.438; p=0.001). We also used the multivariate logistic regression model to assess predictors of mortality in patients admitted with pre-eclampsia. These included age at admission (aOR 1.064; 95% CI 1.009-1.121; p=0.021), Asian/Pacific-Islander race (aOR 4.893; 95% CI 1.884-12.711; p=0.001), and comorbidities such as CHF (aOR 19.405; 95% CI 6.408-58.768; p=0.001), eclampsia (aOR 17.253; 95% CI 5.323-55.924; p=0.001), syndrome of HELLP (hemolysis, elevated liver enzymes, low platelets) (aOR 6.204; 95% CI 2.849-13.510; p=0.001), coagulopathy (aOR 6.524; 95% CI 1.997-21.308; p=0.002), and liver disease (aOR 5.217; 95% CI 1.156-23.554; p=0.032). Conclusion In a large cohort of patients admitted with pre-eclampsia, we found the prevalence of CAD to be 0.1%. CAD was associated with several clinical outcomes, including NSTEMI. Predictors of mortality in patients with pre-eclampsia included demographic variables such as age and Asian race, as well as comorbidities such as CHF and coagulopathy.
PubMed: 38817475
DOI: 10.7759/cureus.59309