Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5951 - 5951

Published: May 29, 2024

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with reduced immune responses stimuli which increase susceptibility infections. Recently, maternal western-style diets (WSDs), high fat simple sugars, been associated skewing neonatal cell development, recent evidence suggests that dysregulation innate immunity early life has long-term consequences metabolic diseases behavioral disorders later Several factors contribute abnormal tolerance or trained immunity, including changes gut microbiota, metabolites, epigenetic modifications. Critical knowledge gaps remain regarding mechanisms whereby these fetal postnatal especially precursor stem cells bone marrow liver. Components microbiota are transferred from consuming WSD their understudied identifying cause effect adaptive development needs be refined. Tools single-cell RNA-sequencing, analysis, spatial location specific liver for understanding system programming. Considering vital role function plays health, it will important understand how control developmental programming immunity.

Language: Английский

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Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

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

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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

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Erythro-myeloid progenitor origin of Hofbauer cells in the early mouse placenta

Development, Journal Year: 2022, Volume and Issue: 149(8)

Published: April 15, 2022

ABSTRACT Hofbauer cells (HBCs) are tissue macrophages of the placenta thought to be important for fetoplacental vascular development and innate immune protection. The developmental origins HBCs remain unresolved could implicate functional diversity in disease. In this study, we used flow cytometry paternally inherited reporters phenotype identify fetal-derived placenta-associated maternal mouse. vivo pulse-labeling traced ontogeny from yolk sac-derived erythro-myeloid progenitors, with a minor contribution fetal hematopoietic stem later on. Single-cell RNA-sequencing revealed transcriptional similarities between progenitor-derived liver microglia. As other macrophages, were dependent on transcription factor Pu.1, loss-of-function which embryos disrupted labyrinth morphology, supporting role HBC angiogenesis and/or remodeling. also sensitive Pu.1 (Spi1) haploinsufficiency, caused an initial deficiency numbers early mouse placenta. These results provide groundwork future investigation into relationship function pathophysiology.

Language: Английский

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Placental macrophage responses to viral and bacterial ligands and the influence of fetal sex

iScience, Journal Year: 2022, Volume and Issue: 25(12), P. 105653 - 105653

Published: Nov. 22, 2022

Bacterial and viral infections of the placenta are associated with inflammation adverse pregnancy outcomes. Hofbauer cells (HBCs) fetal-origin macrophages in placenta, proposed to protect fetus from vertical pathogen transmission. We performed quantitative proteomics on term HBCs under resting conditions following exposure bacterial pathogen-associated molecular patterns (PAMPs), investigated contribution fetal sex. Resting expressed proteins pertinent macrophage function, including chemokines, cytokines, Toll-like receptors, major histocompatibility complex class I II molecules. mounted divergent responses versus PAMPs but exhibited protein expression changes suggestive a more pro-inflammatory phenotype. A comparison between male female showed that latter stronger wider response. Here, we provide comprehensive understanding sex-dependent placental infectious triggers, which were primarily lipid metabolism males cytoskeleton organization females.

Language: Английский

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The Metabolic Journey of Microglia from Early Development to Adulthood

Glial health research., Journal Year: 2024, Volume and Issue: unknown, P. 100003 - 100003

Published: Dec. 1, 2024

Language: Английский

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Maternal obesity and offspring neurodevelopment are associated with hypoxic gene expression in term human placenta

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

Abstract One third of women in the United States are affected by obesity during pregnancy. Maternal (MO) is associated with an increased risk neurodevelopmental and metabolic disorders offspring. The placenta, located at maternal-fetal interface, a key organ determining fetal development likely contributes to programming long-term offspring health. We profiled term placental transcriptome humans (pre-pregnancy BMI 35+ [MO condition] or 18.5-25 [lean condition]) using single-nucleus RNA-seq compare expression profiles MO versus lean conditions, reveal potential mechanisms underlying disease risk. recovered 62,864 nuclei high quality from 10 samples each maternal-facing fetal-facing sides placenta. On both several cell types, was upregulation hypoxia response genes. side only, gene measures, Gen3G, independent pregnancy cohort bulk tissue RNA-seq. leveraged Gen3G determine genes that correlated impaired neurodevelopment found these be most highly expressed extravillous trophoblasts (EVTs). EVTs further showed strongest correlation between impairment scores (NDIGSs) score. reanalyzed cultured EVTs, NDIGSs exposure hypoxia. Among accounting for score attenuated 44% association NDIGSs. These data suggest may process MO.

Language: Английский

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Maternal stressors disrupt mouse placental proteome and fetal brain development in a sex-specific fashion through inflammation and oxidative stress

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

Published: Nov. 15, 2024

Adverse maternal conditions during pregnancy result in an increased risk for neuropsychiatric disorders the offspring, although underlying mechanisms are poorly understood. We have recently shown that two distinct insults, psychophysical stress (PNS) or high-fat diet (mHFD), increase inflammation and oxidative brain of adolescent female mice. Here, we sought to investigate early such effects, focusing on placenta fetal brain, as well protective effects antioxidant N-acetyl-cysteine (NAC), C57Bl6/N used a multi-disciplinary approach combining proteomic, metabolomic, lipidomic histological analysis characterize structural functional changes placenta; moreover, targeted gene expression was carried-out brains male fetuses evaluate inflammatory-related changes. Our data highlight comparable, but sex-specific, responses stressors, which target buffered by NAC administration. Placental function specifically disrupted males, with signaling pathways cardio-metabolic emerging this sex. By contrast, affected females, genes related stress. In conclusion, provide evidence origin sex-dependent embedding prenatal adverse experiences different organs might explain differential susceptibility later disease trajectories.

Language: Английский

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A Review of the Roles of Placental Chorionic Trophoblasts and Macrophages and Trends in Perinatal Research

Perinatology, Journal Year: 2024, Volume and Issue: 35(4), P. 113 - 113

Published: Jan. 1, 2024

Language: Английский

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