Abstract Background Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between ...immunological inflammation and ASD remains uncertain. Methods Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures. Results We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81–1.01, P = 0.08). Conclusions This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.
The universal two-child policy (TCP; 2016) in China has affected many aspects of maternal-neonatal health. A tertiary hospital-based retrospective study (2011-2019) was used to find the association ...of these policy changes with maternal age and pregnancy outcomes in women with AMA (≥ 35 years) in the Hubei Province, China. The proportion of neonatal births to women with AMA increased by 68.8% from 12.5% in the one-child policy (OCP) period to 21.1% in the universal TCP period aOR 1.76 (95% CI: 1.60, 1.93). In the univariate analysis, the proportion of preterm births (29.4% to 24.1%), low birth weight (LBW) (20.9% to 15.9%), and hypertensive disorders of pregnancy (HDP) (11.5% to 9.2%) significantly (p < 0.05) decreased in women with AMA from the OCP period to universal TCP period. However, the proportion of intrauterine growth restriction (IUGR) (0.2% to 0.7%) and gestational diabetes mellitus (GDM) (1.7% to 15.6%) was significantly (p < 0.05) increased over the policy changes. After adjusting for confounding factors, only the risk of GDM increased aOR 10.91 (95% CI: 6.05, 19.67) in women with AMA from the OCP period to the universal TCP period. In conclusion, the risk of GDM increased in women with AMA from the OCP period to the universal TCP period.
Patients with systemic autoimmune diseases, such as systemic lupus erythematosus, were at a higher risk for preeclampsia. The causal relationship between immunological inflammation and preeclampsia ...(PE) remains uncertain. We aimed to investigate the causal relationship between circulating immune inflammation and PE. Genetically predicted blood immune cells and circulating inflammatory proteins were identified using two genome‐wide association studies (GWAS). We used a two‐sample Mendelian randomization (MR) method to determine whether circulating immunological inflammation causes PE. Our findings indicated that ten immunophenotypes were identified to be significantly associated with PE risk: CD62L‐ Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L‐ myeloid Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell Absolute Count, CD62L‐ myeloid Dendritic Cell %Dendritic Cell, CD62L‐ CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L‐ CD86+ myeloid Dendritic Cell Absolute Count, CD16 on CD14+ CD16+ monocyte, HLA DR+ Natural Killer Absolute Count, and T cell Absolute Count. Ninety‐one inflammation‐related proteins had no statistically significant effect on PE following false discovery rate (FDR) correction. Certain proteins exhibited unadjusted low p‐values that merited mention. These proteins include interleukin‐10 (OR = 0.76, 95%CI = 0.63–0.93, p = .006), fibroblast growth factor 21 (OR = 1.23, 95%CI = 1.01–1.47, p = .035), and Caspase 8 (OR = 0.65, 95%CI = 0.50–0.85, p = .001). The ELISA analysis demonstrated elevated levels of FGF‐21 and decreased levels of IL‐10 and Caspase‐8 in the plasma of patients with PE. These findings reveal that immunophenotypes and circulating inflammatory proteins may induce PE, confirming the importance of peripheral Immunity‐Inflammation in PE. The discovery has the potential to lead to earlier detection and more effective treatment techniques.
Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs have been highlighted in human diseases. However, the detailed molecular mechanism of hucMSCs-derived ...exosomal miR-18b-3p on preeclampsia (PE) remains further investigation. We aimed to investigate the effect of exosomes and miR-18b-3p/leptin (LEP) on occurrence of PE. The morphology of the hucMSC and hucMSC-exosomes (Exos) was identified. The exosomes were infected with different lentivirus expressing miR-18b-3p to explore the role of miR-18b-3p in PE. The PE rat model was established by intraperitoneal injection of N-nitro-L-arginine methyl ester. The expression of LEP and miR-18b-3p was tested in PE rat placenta tissues. Also, the effect of exosomes on LEP and miR-18b-3p expression was detected. The systolic blood pressure (SBP), proteinuria, inflammatory factors, the weight of fetal rat and placenta and cell apoptosis in PE rats were detected. Finally, the relationship between miR-18b-3p and LEP was verified using dual-luciferase reporter gene assay and RNA pull-down assay. Exosomes, restoring miR-18b-3p or inhibiting LEP reduced SBP and proteinuria of PE rats as well as increased the weight of fetal rat and placenta, decreased serum levels of inflammatory factors as well as suppressed apoptotic cells of PE rats, exerting a suppressive effect on PE progression. miR-18b-3p was decreased and LEP was increased in placenta tissues of PE rats. LEP was the direct target gene of miR-18b-3p. Upregulation of miR-18b-3p or treatment of the exosomes suppressed LEP expression and reduced PE occurrence, while downregulation of miR-18b-3p had contrary effects. Downregulated LEP reversed the effect of miR-18b-3p reduction on PE rats. HucMSCs-derived exosomal miR-18b-3p targets LEP to participate in the occurrence and development of PE. This study may provide a novel theoretical basis for the mechanism and investigation of PE.
Preeclampsia (PE) is a pregnancy complication beginning after 20 weeks of pregnancy that involves high blood pressure (systolic > 140 mmHg or diastolic > 90 mmHg), with or without proteinuria. ...Insufficient trophoblast invasion and abnormal decidualization are involved in PE development. However, whether unhealthy placenta and decidua have the same biological activities is unclear. The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by
) degrades prostaglandin, and prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, helps transport prostaglandin into cells. Whether 15-PGDH and PGT are involved in PE has not been researched. In this study, we investigated the shared pathogenesis of foetal placenta and maternal decidua from the perspective of epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) and explored the combined effects of 15-PGDH and PGT on the EMT/MET of trophoblasts and decidual stromal cells (DSCs). Here, we demonstrated that placental development and decidualization both involved EMT/MET. In PE, both trophoblasts and DSCs show more epithelial patterns. Moreover, 15-PGDH expression was downregulated in the placentas but upregulated in the deciduas of PE patients. Inhibiting 15-PGDH promotes a shift to a mesenchymal pattern of trophoblasts and DSCs depending on the PGT-mediated transport of prostaglandin E2 (PGE2). In conclusion, our results showed that inhibiting 15-PGDH promotes a shift to the mesenchymal pattern of trophoblasts and DSCs and may provide a new and alternative therapy for the treatment of PE.
Prostaglandins participate in maternal recognition of pregnancy, implantation and maintenance of gestation. Prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, might ...be involved in the pathogenesis of preeclampsia. In preeclampsia (PE) patients’ placental tissue, we identified PGT by RNA sequencing, measured its expression pattern by quantitative real-time PCR and Western blot. PGT was found to be upregulated in preeclamptic placental tissue. The expression pattern of PGT in PE was double confirmed by eight Gene Expression Omnibus (GEO) databases. In abortion tissues at 6–8 weeks, we then observed the cellular location of PGT by Immunofluorescence technique (IF) and found PGT located in trophoblast cell of the placenta of early pregnancy. In vitro studies revealed that forced expression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation by activating Erk signaling. In vivo study, we used reduced uterine perfusion pressure (RUPP) rat model and L-NAME-induced preeclampsia-like rats to study the possible role of PGT in preeclampsia. And PGT was found to be upregulated in both preeclampsia rat models by Immunohistochemical (IHC) staining. Newly identified PGT plays an important role in trophoblast proliferation via Erk signaling, providing new insights for understanding the pathogenesis of PE.
•PGT was upregulated in preeclamptic placental tissue and preeclampsia rat model.•Erk signaling inhibited HTR8/Sveno apoptosis, but promoted its proliferation.•The overexpression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation via Erk signaling.
To explore the clinical characteristics and placental pathological changes of pregnant women with 2019 novel coronavirus (CoV) disease (COVID-19) in the third trimester, and to assess the possibility ...of vertical transmission.
The placenta tissues were evaluated by using immunohistochemistry for inflammatory cells and Hofbauer cells, and using severe acute respiratory syndrome (SARS) CoV-2 RNA Fluorescence In-Situ Hybridization (FISH) and SARS-CoV-2 spike protein immunofluorescence (IF) double staining. All eight placentas from the third trimester pregnancy women were studied. All patients were cured, no clinical or serological evidence pointed to vertical transmission of SARS-CoV-2. Features of maternal vascular malperfusion (MVM) such as increased syncytial knots were present in all 8 cases (8/8), and increased focal perivillous fibrin depositions were presented in 7 cases (7/8). No significate chronic histiocytic intervillositis was noted in the placenta. The number of macrophages and inflammatory cells such as T cells, B cells and plasma cells in the placental villous was not significantly increased in all cases. Moreover, all of eight cases demonstrated negative results by FISH using a SARS-CoV-2 virus RNA probe and by IF using a monoclonal antibody against SARS-CoV-2 spike protein.
We found no evidence of vertical transmission and adverse maternal-fetal outcomes in the placentas of third trimester COVID-19 pregnancy women, which provided further information for the clinical management of those women in the third trimester. However, further studies are still needed for patients with infections in different stage of gestation, especially in first and second trimester.
Abstract
Background
Due to the advancement of modern societies, the proportion of women who delay childbearing until or beyond 30 years has dramatically increased in the last three decades and has ...been linked with adverse maternal-neonatal outcomes.
Objective
To determine the trend in delayed childbearing and its negative impact on pregnancy outcomes.
Material and methods
A tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital, Hubei Province, China, during the years 2011–2019. The joinpoint regression analysis was used to find a trend in the delayed childbearing and the multiple binary logistic regression model was used to estimate the association between maternal age and pregnancy outcomes.
Results
Between 2011 and 2019, the trend in advanced maternal age (AMA ≥35 years) increased by 75% AAPC 7.5% (95% CI: − 10.3, 28.9). Based on maternal education and occupation, trend in AMA increased by 130% AAPC 11.8% (95% CI: 1.1, 23.7) in women of higher education level, and 112.5% AAPC 10.1% (95% CI: 9.4, 10.9) in women of professional services. After adjusting for confounding factors, AMA was significantly associated with increased risk of gestational hypertension (aOR 1.5; 95% CI: 1.2, 2.1), preeclampsia (aOR 1.6; 95% CI: 1.4, 1.9), sever preeclampsia (aOR 1.7; 95% CI: 1.1, 2.6), placenta previa (aOR 1.8; 95% CI: 1.5, 2.2), gestational diabetes mellitus (aOR 2.5; 95% CI: 2.3, 2.9), preterm births (aOR 1.6; 95% CI: 1.4, 1.7), perinatal mortality (aOR 1.8; 95% CI: 1.3, 2.3), and low birth weight (aOR 1.3; 95% CI: 1.2, 1.4) compared with women aged < 30 years.
Conclusion
Our findings show a marked increase in delayed childbearing and its negative association with pregnancy outcomes.
Pre-eclampsia (PE) is a gestational hypertensive disorder that is characterized by hypertension and proteinuria, typically occurring after 20 weeks of gestation. Despite its global impact on pregnant ...women, the precise pathogenic mechanisms of PE remain unclear. Dysregulated lipid metabolism and immune cell infiltration contribute to PE development. Our study aimed to identify lipid-metabolism-related genes (LMRG-PEs) and investigate their association with immune infiltration. We utilized the “Seurat” R package for data quality control, cell clustering, and marker gene identification. The “SingleR” package enabled the matching of marker genes to specific cell types. Pseudotemporal ordering analysis was conducted using the “Monocle” package. Weighted correlation network analysis (WGCNA), gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) approaches were employed to explore lipid-metabolism-related genes, while potential targeted drugs were predicted using the drug–gene interaction database (DGIdb). Hub gene expression was validated through RT–qPCR. By analyzing single-cell RNA sequencing data, we identified and classified 20 cell clusters into 5 distinct types. Differential gene expression analysis revealed 186 DEGs. WGCNA identified 9 critical modules and 265 genes significantly associated with PE diagnosis, emphasizing the importance of the core genes PLA2G7 and PTGS2. RT–qPCR confirmed the significantly decreased expression of PLA2G7 and PTGS2 in PE patient tissues. These findings offer valuable insights into the molecular mechanisms of PE, particularly those involving lipid metabolism and immune infiltration. The identified hub genes have potential as therapeutic targets and biomarkers for future research and clinical applications.
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