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

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Timing matters: modeling the effects of gestational cannabis exposure on social behavior and microglia in the developing amygdala

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Cannabis is the most frequently used illicit drug during pregnancy, with use steadily increasing in United States as legalization and decriminalization expand to more states. Many pregnant individuals cannabis reduce adverse symptoms of considering it be less harmful than other pharmaceuticals or alcohol. The primary psychoactive component cannabis, delta-9-tetrahydrocannabinol (THC), acts on endocannabinoid (eCB) system, yet whether perturbs neural development fetus poorly understood. Previously we have shown that androgen mediated eCB tone developing amygdala promotes microglial phagocytosis newborn astrocytes which has enduring consequences circuits regulating sex differences social behavior. Microglia are resident immune cells brain express both receptors CB1R CB2R, making them likely targets modulation by THC. It also plausible exposure THC at differing gestational timepoints can result distinct outcomes, case alcohol exposure. To model human either late early exposed rodents directly postnatal period via intraperitoneal (IP) injection utero prenatal dam IP respectively. Here show results specific changes well behavior juvenile period. Interestingly resulted inverse These findings highlight differential effects across gestation.

Language: Английский

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The Hallmarks of Ageing in Microglia

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: May 19, 2025

Abstract As ageing is linked to the development of neurodegenerative diseases (NDs), such as Alzheimer’s Disease and Parkinson’s Disease, it important disentangle independent effect age-related changes from those due disease processes. To do so, central nervous system (CNS) cells a function advanced age need better characterisation. Microglia are particular interest their proposed links with progression NDs through control CNS immune response. Therefore, understanding extent which microglial dysfunction related phyisological ageing, rather than process, critical. microglia age, they believed take on pro-inflammatory phenotype distinct dystrophic morphology. Nevertheless, while established hallmarks have been investigated across range other cell types, macrophages, detailed consideration functional that occur in aged remains elusive. Here, we describe dynamic phenotypes evaluate current state focusing recently updated twelve ageing. Understanding how these present represents step towards characterisation essential more representative models NDs. Graphical Microglial different stages life. diverse functions throughout life; however, has inconsistent

Language: Английский

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Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract Effective communication between different cell types is essential for brain health, and dysregulation of this process leads to neuropathologies. Brain glial cells, including microglia astrocytes, orchestrate immune defense neuroimmune responses under pathological conditions during which interglial indispensable. Our appreciation the complexity these processes rapidly increasing due recent advances in molecular biology techniques, have identified numerous phenotypic states both astrocytes. This review focuses on microglia-to-astrocyte facilitated by secreted modulators. The combinations interleukin (IL)-1α, tumor necrosis factor (TNF), plus complement component C1q as well IL-1β TNF are already well-established microglia-derived stimuli that induce reactive phenotypes However, given large number inflammatory mediators distinct functional recognized it can be hypothesized many more intercellular signaling molecules exist. identifies following group cytokines gliotransmitters that, while not established yet, known released elicit astrocytes: IL-10, IL-12, IL-18, transforming growth (TGF)-β, interferon (IFN)-γ, C–C motif chemokine ligand (CCL)5, adenosine triphosphate (ATP), l -glutamate, prostaglandin E2 (PGE2). mechanisms engaged reveals complex, partially overlapping pathways implicated Additionally, lack human-specific studies a significant knowledge gap. Further research warranted, could discover novel signaling-targeted therapies diverse neurological disorders.

Language: Английский

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Microbiome and Pregnancy Dysbiosis: A Narrative Review on Offspring Health

Nutrients, Journal Year: 2025, Volume and Issue: 17(6), P. 1033 - 1033

Published: March 15, 2025

Background: Emerging evidence suggests that the maternal microbiome plays a crucial role in shaping fetal neurodevelopment, immune programming, and metabolic health. Dysbiosis during pregnancy—whether gastrointestinal, oral, or vaginal—can significantly influence pregnancy outcomes long-term child Materials Methods: The search was performed using databases such as PubMed, Scopus, Google Scholar including research published from January 2000 to 2025. keywords used were “Fetal Programming”, “ Maternal Immune Activation”, “Maternal microbiome”, “Microbiota–Gut–Brain Axis”, “Pregnancy Dysbiosis”. Results: undergoes substantial changes pregnancy, with alterations microbial diversity function linked conditions gestational diabetes, obesity, preeclampsia. Pregnancy-related dysbiosis has been associated adverse neurodevelopmental outcomes, an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity (ADHD), cognitive impairments offspring. Conclusions: Understanding intricate relationship between microbiota health is essential for developing targeted interventions. Personalized microbiome-based strategies, dietary modifications probiotic supplementation, hold promise optimizing promoting

Language: Английский

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From womb to world: The interplay between maternal immune activation, neuroglia, and neurodevelopment

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 269 - 285

Published: Jan. 1, 2025

Language: Английский

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The Complementary Role of Morphology in Understanding Microglial Functional Heterogeneity

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3811 - 3811

Published: April 17, 2025

A search of the PubMed database for publications on microglia reveals an intriguing shift in scientific interest over time. Dividing into categories such as “resting” and “activated” or M1 versus M2 is nowadays obsolete, with current research focusing unraveling microglial heterogeneity. The onset transcriptomics, especially single-cell RNA sequencing (scRNA-seq), has profoundly reshaped our understanding Conversely, morphology analysis can offer important insights regarding their activation state involvement tissue responses. This review explores heterogeneity under homeostatic conditions, developmental stages, disease states, a focus integrating transcriptomic data morphological analysis. Beyond core gene expression profile, regional differences are observed cerebellar exhibiting uniquely immune-vigilant profile. During development, express genes before birth, yet bushy appearance characteristic that appears later on. In neurodegeneration, alternate between proinflammatory neuroprotective roles, influenced by factors onset. Understanding these structural adaptations may help identify specific subpopulations targeted therapeutic strategies.

Language: Английский

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Inflammation in Schizophrenia: The Role of Disordered Oscillatory Mechanisms

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 650 - 650

Published: April 29, 2025

Schizophrenia is a chronic, debilitating disorder with diverse symptomatology, including disorganised cognition and behaviour. Despite considerable research effort, we have only limited understanding of the underlying brain dysfunction. A significant proportion individuals schizophrenia exhibit high levels inflammation, inflammation associated maternal immune system activation risk factor for disorder. In this review, outline potential role in disorder, particular focus on how cytokine release might affect development function GABAergic interneurons. One consequence change inhibitory control disruption oscillatory processes brain. These changes disrupt spatial temporal synchrony neural activity brain, which, by disturbing representations time space, may underlie some disorganisation symptoms observed

Language: Английский

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Beyond Infections: Exploring Immune-Mediated Pathways Linking Cannabis and Emerging Environmental Contaminants to Neurodevelopmental Outcomes

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 281 - 309

Published: Jan. 1, 2025

Language: Английский

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Brain-Resident Immune Cells in Neurodevelopmental Disorders

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 265 - 280

Published: Jan. 1, 2025

Language: Английский

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