The immune landscape of fetal chorionic villous tissue in term placenta

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 13, 2025

Introduction The immune compartment within fetal chorionic villi is comprised of Hofbauer cells (HBC) and invading placenta-associated maternal monocytes macrophages (PAMM). Recent studies have characterized the transcriptional profile first trimester (T1) placenta; however, phenotypic functional diversity villous at term (T3) remain poorly understood. Methods To address this knowledge gap, from human tissues obtained full-term, uncomplicated pregnancies were deeply phenotyped using a combination flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) chromatin accessibility profiling (snATAC-seq). Results Our results indicate that, relative to trimester, frequency (HBC, proliferating HBC) significantly reduced, whereas that infiltrating monocytes/macrophages (PAMM1b, PAMM1a, PAMM2, MAC_1) increased in T3. PAMM1b HBCs exhibit most phagocytic capacity highlighting their regulatory role tissue homeostasis late pregnancy. profiles resident subsets heightened activation state T1, likely support labor parturition. Additionally, we provide one insights into myeloid term. We next stratified our findings by pre-pregnancy BMI since pregravid obesity associated with several adverse pregnancy outcomes. Pregravid inflammatory gene expression, particularly among HBC PAMM1a subsets, but dampened expression antimicrobial genes, supporting tolerant-like phenotype cells. report decline abundance accompanied an increase macrophages, which aligns reports pathologies obesity. Finally, given shared yolk-sac origin microglia, leveraged vitro model umbilical cord blood-derived microglia investigate impact on neurodevelopment. reveal markers albeit Discussion Overall, study highlights adaptations gestational age obesity, as well insight towards dysfunction possibly underlying poor neurodevelopmental outcomes offspring women

Language: Английский

---

Assessing in-vitro models for microglial development and fetal programming: a critical review

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

This review evaluates in-vitro models for studying how maternal influences during pregnancy impact the development of offspring microglia, immune cells central nervous system. The examined include primary microglia cultures, cell lines, iPSC-derived PBMC-induced microglia-like cells, 3D brain organoids derived from iPSCs, and Hofbauer cells. Each model is assessed its ability to replicate in-vivo environment developing brain, with a focus on their strengths, limitations, practical challenges. Key factors such as scalability, genetic epigenetic fidelity, physiological relevance are highlighted. Microglia lines highly scalable but lack fidelity. provide moderate patient-specific insights face operational challenges inherent reprogramming. organoids, offer an advanced platform complex neurodevelopmental processes require extensive resources technical expertise. which fetal macrophages located in placenta share common developmental origin uniquely exposed prenatal and, depending barrier maturation, exhibit variable makes them particularly useful exploring programming microglial development. concludes that no single comprehensively captures all aspects development, it offers guidance selecting most appropriate based specific research objectives experimental constraints.

Language: Английский

---

Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19

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

---

In Situ Analyses of Placental Inflammatory Response to SARS-CoV-2 Infection in Cases of Mother–Fetus Vertical Transmission

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8825 - 8825

Published: Aug. 13, 2024

It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there still limited information on specific impact maternal infection transmission. The current study focuses a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother-newborn pairs affected by COVID-19 those unaffected controls. Additionally, it investigates situ molecules involved placental inflammation. Papa Giovanni XXIII Hospital Bergamo, Italy, recorded three instances intrauterine SARS-CoV-2. first two cases occurred early pandemic pregnant women their third trimester who were diagnosed with case an asymptomatic woman her second twin pregnancy, unfortunately delivered stillborn fetuses due to premature rupture membranes. Transcriptomic revealed significant placentae COVID-19-affected mother/newborn matched infected control for gestational age. According Benjamani-Hochberg method, 305 genes met criterion adjusted p-value less than 0.05, 219 0.01. Up-regulated cell signaling (e.g., CCL20, C3, MARCO) immune response LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest potential role inflammatory RNAscope® technology, coupled image analysis, was utilized quantify surface area covered SARS-CoV-2, ACE2, IL-1β, IL-6, IL-8, IL-10, TNF-α both fetal sides placenta. A non-statistically gradient observed, higher coverage side (2.42 ± 3.71%) compared (0.74 1.19%) Although not statistically significant, ACE2 mRNA (0.02 0.04%) (0.01 0.01%) IL-6 IL-8 more prevalent (0.03 0.04% 0.06 0.08%, respectively) 0.01% 0.02 0.02%, respectively). mean areas IL-1β IL-10 found be equal (0.04 0.01 0.01%, placenta 0.05% 0.02% On side, ACE-2 all examined interleukins, but TNF-α, exhibited inverse amount ACE-2, inversely correlated (r = -0.3, r -0.1 -0.4, respectively), while showed positive correlations 0.9, p 0.005 0.5, correlation 0.4) 0.9) Further research needed evaluate Nonetheless, extends our comprehension molecular immunological factors underlying maternal-fetal

Language: Английский

---

SARS-CoV-2 and Offspring Neurodevelopment—We Don’t Know Yet

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(10), P. e2439799 - e2439799

Published: Oct. 16, 2024

Eleni G. Jaswa, MD, MSc, MAS; Heather Huddleston, MD; Karla J. Lindquist, PhD; Alan H. B. Wu, Somer L. Bishop, Young-Shin Kim, MS, MPH, Amy Kaing, Mary Prahl, Stephanie Gaw, Jamie Corley, BS; Elena Hoskin, MS; Yoon Jae Cho, Elizabeth E. Rogers, Marcelle I. Cedars, MD

Language: Английский

---

The impact of SARS-CoV-2 infection at different stages of pregnancy on placental inflammatory responses

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

Published: Nov. 1, 2024

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

---