The impact of SARS-CoV-2 infection at different stages of pregnancy on placental inflammatory responses DOI Creative Commons
Mengyue Yin, Lingling Peng,

Chunling Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Background The specific impact and pathology of SARS-CoV-2 infection on maternal fetal health have not been comprehensively investigated. Therefore, we investigated the inflammatory response tissues in pregnant women infected with at different stages pregnancy. Methods We collected placenta samples from 52 patients Tai’an Central Hospital, who underwent delivery between November 2022 September 2024. analyzed general patient data maternal-fetal outcomes conducted histological observations using HE staining. Furthermore, used ELISA to quantitatively analyze concentration IL-6 umbilical cord blood amniotic fluid. Additionally, Western blot analysis was evaluate expression levels TNF-α IL-1β placental tissues. Results Among participants, 33 were diagnosed infection. Patients during mid-pregnancy developed thrombosis, stromal protein deposition, villous interstitial inflammation compared control group (P < 0.05). However, No significant differences found late-term > revealed elevated tissues, no difference mid-term pregnancies. fluid showed difference, detected blood. Conclusion pregnancy appears limited overall outcomes. may lead changes particularly mid-trimester. These findings suggest importance careful monitoring management women. Nonetheless, larger studies are necessary confirm these explore long-term effects both health.

Language: Английский

SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics DOI Creative Commons
Enrico R. Barrozo, Maxim D. Seferovic, Eumenia Castro

et al.

Med, Journal Year: 2023, Volume and Issue: 4(9), P. 612 - 634.e4

Published: July 8, 2023

BackgroundFunctional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map transcription could provide direct evidence for niche microenvironments with unique functions profiles.MethodsWe utilized Visium Spatial Transcriptomics paired H&E staining generate 17,927 spatial transcriptomes. By integrating these transcriptomes 273,944 single-cell single-nuclei transcriptomes, we generated an atlas composed at least 22 subpopulations in maternal decidua, fetal chorionic villi, chorioamniotic membranes.FindingsComparisons placentae from uninfected healthy controls (n = 4) COVID-19 asymptomatic symptomatic 5) infected participants demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection syncytiotrophoblasts occurred both presence absence clinical disease. With transcriptomics, found limit SARS-CoV-2 was 1/7,000 cells, without detectable viral transcripts were unperturbed. In contrast, high transcript levels associated significant upregulation pro-inflammatory cytokines interferon-stimulated genes, altered metallopeptidase signaling (TIMP1), coordinated shifts macrophage polarization, histiocytic intervillositis, perivillous fibrin deposition. Fetal sex differences gene expression responses limited, confirmed mapping limited decidua males.ConclusionsHigh-resolution transcriptomics resolution revealed dynamic coordinate clinically evident disease.FundingThis work supported by NIH (R01HD091731 T32-HD098069), NSF (2208903), Burroughs Welcome Fund March Dimes Preterm Birth Research Initiatives, Career Development Award American Society Gene Cell Therapy.

Language: Английский

Citations

18
Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal–fetal interface following SARS-CoV-2 infection DOI Creative Commons
Lin Gao, Vrinda Mathur, Sabrina Ka Man Tam

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(7), P. 1047 - 1060

Published: July 1, 2023

During pregnancy the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found complications. Recent studies show increased incidences of adverse outcomes patients with COVID-19; however, mechanism remains unclear. Here we analysed molecular impacts SARS-CoV-2 infection on interface. Generating bulk and single-nucleus transcriptomic epigenomic profiles from COVID-19 control samples, discovered aberrant immune activation angiogenesis patterns distinct cells patients. Surprisingly, retrotransposons were also dysregulated specific cell types. Notably, reduced enhancer activities LTR8B elements functionally linked to downregulation pregnancy-specific glycoprotein genes syncytiotrophoblasts. Our findings revealed that induced substantial changes epigenome transcriptome at interface, which may be associated

Language: Английский

Citations

16
Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy DOI Creative Commons
Chenxiang Xi, Zihui Yan, Dandan Bai

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 460 - 473

Published: March 5, 2024

Abstract The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early pregnancy SARS-CoV-2 infection on maternal-fetal interface poorly understood. Here, we present comprehensive analysis single-cell transcriptomics and metabolomics in placental samples infected with during pregnancy. Compared control placentas, elicited immune responses at induced metabolic alterations amino acid phospholipid profiles initial weeks post-infection. subsequent cell activation heightened tolerance trophoblast cells established novel dynamic equilibrium that mitigated interface. Notably, response exhibited gradual decline second trimester. Our study underscores adaptive mechanisms establishment immunological balance first two trimesters following maternal infection.

Language: Английский

Citations

6
Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment DOI Creative Commons
Lydia L. Shook, Rebecca Batorsky, Rose M. De Guzman

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 25, 2024

Abstract Background The SARS-CoV-2 virus activates maternal and placental immune responses. Such activation in the setting of other infections during pregnancy is known to impact fetal brain development. effects on neurodevelopment are mediated at least part by microglia. However, microglia inaccessible for direct analysis, there no validated non-invasive surrogate models evaluate utero microglial priming function. We have previously demonstrated shared transcriptional programs between Hofbauer cells (HBCs, or macrophages) mouse models. Methods results assessed HBCs isolated from 24 term placentas ( N = 10 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we that HBC subpopulations exhibit distinct cellular programs, with specific differentially impacted SARS-CoV-2. Assessment expressed genes implied impaired phagocytosis, a key function both microglia, some subclusters. Leveraging synaptic pruning, showed pregnancies can be transdifferentiated into microglia-like (HBC-iMGs), pruning behavior compared controls. Conclusion These findings suggest birth used create personalized offspring programming.

Language: Английский

Citations

6
Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity DOI Creative Commons
Suhas Sureshchandra, Brianna M. Doratt, Heather True

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(7), P. 112769 - 112769

Published: July 1, 2023

Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, immunological landscape term decidua remains poorly understood. We therefore profiled human leukocytes from collected via scheduled cesarean delivery. Relative to first trimester, our analyses show a shift NK cells and macrophages T enhanced immune activation. Although circulating decidual are phenotypically distinct, they demonstrate significant clonotype sharing. also report within macrophages, frequency which positively correlates with pregravid maternal body mass index. Interestingly, ability respond bacterial ligands is reduced obesity, suggestive skewing toward immunoregulation as possible mechanism safeguard fetus against excessive inflammation. These findings resource for future studies investigating pathological conditions that compromise fetal health reproductive success.

Language: Английский

Citations

13
Therapeutic implications of endoplasmic reticulum stress gene CCL3 in cervical squamous cell carcinoma DOI Creative Commons
Yingping Zhu, Wei Xu, Yuanfang He

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 20, 2025

This study investigated ERS-related gene expressions in CESC, identifying two molecular subtypes, P1 and P2, constructing a precise prognostic model based on these subtypes. TCGA's whole-genome expression profiles were used to recognize subtypes through the ConsensusClusterPlus method, further refining models with univariate Lasso Cox regression analyses validated by GSE39001 dataset. The analyzed distribution of ERS marker genes within T cell subgroups using scRNA-seq data (GSE168652), highlighting diversity. critical role CCL3 was examined explicitly CD8 + cells from healthy individuals CESC patients. Elevated levels observed patients' compared controls. Functional experiments involving knockdown overexpression HeLa SiHa lines conducted investigate its impact proliferation, migration, invasion. These findings subsequently nude mouse model. results demonstrated that suppressing inhibited invasion significantly, while promoted processes. In model, silencing reduced tumor growth decreased Ki-67 labeling tissues, indicating therapeutic potential targeting treatment, possibly regulation. contributes new assessment tools personalized treatment options for patients, paving way more targeted therapies discovering gene, presenting significant clinical implications.

Language: Английский

Citations

0
Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19 DOI Creative Commons
Rachel A. Keuls, Scott A. Ochsner, Mary B. O’Neill

et al.

American Journal of Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: 232(4), P. S160 - S175.e7

Published: April 1, 2025

COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology function unclear. This study aimed to determine the effects of maternal syncytiotrophoblasts using single-nucleus transcriptional profiling compare stress responses preeclampsia. For characterization syncytiotrophoblasts, we used RNA sequencing platform, single-cell combinatorial indexing (sci-RNA-seq3), profile villi fetal membranes from unvaccinated patients symptomatic at birth (n = 4), gestational age-matched controls a case critical second trimester delivery term 1). Clustering nuclei differential gene expression analysis was performed Seurat. Gene ontology conducted Enrichr. High-confidence target identify key transcription factor nodes governing response SARS-CoV-2 infection. Bioinformatic approaches were further dataset published preeclampsia signatures. Tissue analysis, including immunofluorescence, validate data histology for an expanded cohort placentas: 6), asymptomatic 3), 5), severe features 7). The analyzed comprised 15 cell clusters 47,889 nuclei. We identified 3 representing fusing mature overlapping distinct COVID-19. analyses indicated that following alterations syncytiotrophoblasts: (1) endoplasmic reticulum activation signaling pathways, unfolded protein integrated response; (2) regulation by CCAAT/enhancer-binding beta (CEBPB), master lineage; (3) upregulation preeclampsia-associated genes. Using complementary methods, confirmed increased levels proteins (eg, BiP, G3BP1) (spliced XBP1 mRNA), CEBPB (phosphorylation) Increased cytotrophoblast proliferation (Ki-67) also detected COVID-19, consistent trophoblast injury. Markers demonstrated similarities phenotype Maternal lineage factor, CEBPB. Similarities between provide insights into their clinical association.

Language: Английский

Citations

0
The maternal-fetal interface at single-cell resolution: uncovering the cellular anatomy of the placenta and decidua DOI
Dustyn Levenson, Roberto Romero, Derek Miller

et al.

American Journal of Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: 232(4), P. S55 - S79

Published: April 1, 2025

Language: Английский

Citations

0
Omics approaches: interactions at the maternal–fetal interface and origins of child health and disease DOI Open Access
Maide Özen, Nima Aghaeepour, Ivana Marić

et al.

Pediatric Research, Journal Year: 2022, Volume and Issue: 93(2), P. 366 - 375

Published: Oct. 10, 2022

Language: Английский

Citations

15
Mild/asymptomatic COVID-19 in unvaccinated pregnant mothers impairs neonatal immune responses DOI Creative Commons
Brianna M. Doratt, Suhas Sureshchandra, Heather True

et al.

JCI Insight, Journal Year: 2023, Volume and Issue: 8(19)

Published: Sept. 12, 2023

Maternal SARS-CoV-2 infection triggers placental inflammation and alters cord blood immune cell composition. However, most studies focus on outcomes of severe maternal infection. Therefore, we analyzed chorionic villi from newborns unvaccinated mothers who experienced mild/asymptomatic during pregnancy. We investigated rewiring using flow cytometry, single-cell RNA sequencing, functional readouts ex vivo stimulation with TLR agonists pathogens. was associated increased frequency memory T B cells nonclassical monocytes in blood. Ex responses to were attenuated, suggesting a tolerogenic state. Maladaptive also observed monocytes, where antiviral dampened but bacterial TLRs increased. expansion activation Hofbauer cells, secreting elevated levels myeloid cell–recruiting chemokines. Moreover, reported maternally derived monocytes/macrophages the fetal placenta that transcriptionally primed for responses. Our data indicate even absence vertical transmission or symptoms neonate, COVID-19 altered transcriptional state circulation placenta.

Language: Английский

Citations

9