Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA226614 | ENA |
REPOSITORIES: ENA
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Project description:TNF is a proinflammatory cytokine with established roles in host defense and immune system organogenesis. Here we report a novel physiological function of TNF that extends its effect beyond the host into the developing offspring. A partial/complete maternal TNF-deficit, specifically in hematopoietic cells, resulted in reduced milk levels of chemokines IP-10, MCP-1/-3/-5, and MIP-1β, which in turn, augmented offspring postnatal hippocampal proliferation, leading to improved adult spatial memory. These effects were reproduced by the postpartum administration of a clinically used anti-TNF agent. Chemokines, fed to suckling pups of TNF-deficient mothers, restored both postnatal proliferation and adult spatial memory to normal levels. This work identifies a TNF-dependent “lactrocrine” pathway that programs offspring hippocampal development and memory. The level of ambient TNF is known to be downregulated by physical activity/exercise and adaptive stress; thus, we propose that the maternal TNF-milk chemokine pathway evolved to promote offspring adaptation to post-weaning environmental challenges/competition. Examined transcriptomes of TNF wild type offspring of TNF wild type or heterozygouse mothers
2013-12-01 | E-GEOD-52069 | biostudies-arrayexpress
Project description:TNF is a proinflammatory cytokine with established roles in host defense and immune system organogenesis. Here we report a novel physiological function of TNF that extends its effect beyond the host into the developing offspring. A partial/complete maternal TNF-deficit, specifically in hematopoietic cells, resulted in reduced milk levels of chemokines IP-10, MCP-1/-3/-5, and MIP-1β, which in turn, augmented offspring postnatal hippocampal proliferation, leading to improved adult spatial memory. These effects were reproduced by the postpartum administration of a clinically used anti-TNF agent. Chemokines, fed to suckling pups of TNF-deficient mothers, restored both postnatal proliferation and adult spatial memory to normal levels. This work identifies a TNF-dependent “lactrocrine” pathway that programs offspring hippocampal development and memory. The level of ambient TNF is known to be downregulated by physical activity/exercise and adaptive stress; thus, we propose that the maternal TNF-milk chemokine pathway evolved to promote offspring adaptation to post-weaning environmental challenges/competition.
2013-12-01 | GSE52069 | GEO
Project description:Maternal metabolic dysfunction-associated steatotic liver disease (MASLD) in mice creates a paradoxical neonatal ketone deficit during nursing, despite preserved hepatic ketogenesis, that precedes adult spatial memory impairment. Vulnerable litters show reduced β-hydroxybutyrate (β-HB) in the intestinal lumen, serum, and hippocampus. Increased milk bile-acid hydrophobicity is identified as an upstream determinant of a restrictive neonatal gut niche that suppresses microbiome-dependent depolymerization of poly-β-hydroxybutyrate (PHB) and limits portal β-HB delivery. Early hydrophilization of the neonatal bile-acid pool reopens this gut-to-brain ketone pathway, restores hippocampal β-HB, and prevents later memory impairment, whereas parenteral D-βHB bypass rescues brain ketone availability without correcting the upstream gut defect. A milk bile-acid hydrophobicity threshold prospectively identifies the rescuable high-risk state. These findings define a transferable postnatal metabolic checkpoint upstream of the liver.
2026-08-02 | MTBLS15224 | MetaboLights
Project description:<p>Maternal metabolic dysfunction-associated steatotic liver disease (MASLD) in mice creates a paradoxical neonatal ketone deficit during nursing, despite preserved hepatic ketogenesis, that precedes adult spatial memory impairment. Vulnerable litters show reduced β-hydroxybutyrate (β-HB) in the intestinal lumen, serum, and hippocampus. Increased milk bile-acid hydrophobicity is identified as an upstream determinant of a restrictive neonatal gut niche that suppresses microbiome-dependent depolymerization of poly-β-hydroxybutyrate (PHB) and limits portal β-HB delivery. Early hydrophilization of the neonatal bile-acid pool reopens this gut-to-brain ketone pathway, restores hippocampal β-HB, and prevents later memory impairment, whereas parenteral D-βHB bypass rescues brain ketone availability without correcting the upstream gut defect. A milk bile-acid hydrophobicity threshold prospectively identifies the rescuable high-risk state. These findings define a transferable postnatal metabolic checkpoint upstream of the liver.</p>
2026-08-02 | MTBLS15225 | MetaboLights
Project description:There is little information regarding the allergen content of milk feeds in the preterm population. Previous studies have evaluated specific proteins/peptides via ELISA, but no studies have performed a broad analysis of the allergenic peptide content and protease activity of milk feeds in this population. Preterm infants spend a critical window of time for immune development in the Newborn Intensive Care Unit (NICU), and may receive fortified donor milk, maternal milk or formula feeds via nasogastric tube or bottle instead of fresh breastmilk via breastfeeding.
2024-01-26 | PXD033473 | Pride
Project description:Breast milk is associated with multiple benefits for the infant, including reduced incidence of chronic diseases such as Inflammatory Bowel Disease. We investigated the role of milk-derived maternal IgA (matIgA) on the developing small intestinal immune system. Using a model, where genotypically identical pups were fed by dams differed only in IgA production we revealed that matIgA regulates the assembly of the infant small intestinal microbiota and epithelium, supporting Lactobacillaceae and suppressing Enterobacteriaceae and the development of secretory lineage cells. Via the microbiota, MatIgA also regulated infant immune cells and suppressed early activation of Th17 cells. We demonstrated that Enterobacteriaceae-specific CD4+ T cells, activated in the absence of matIgA, persisted long term where they may contribute to subsequent inflammatory episodes. This work suggests that maternal IgA shapes the mucosal immune response by regulating the early-life microbiota thus preventing the development of inflammatory microbiota-specific T cells with memory potential.
2024-02-16 | GSE255576 | GEO
Project description:Maternal health and diet can have important consequences for offspring nutrition and metabolic health. Signals are communicated from the mother to the infant during lactation through milk via macronutrients, hormones and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring beginning to wean. We found that lactational HFD increased maternal adipose tissue, mammary gland adipocytes, and altered milk lipid composition causing a higher amount of n-6 long chain fatty acids and lower n-3. Offspring of HFD dams were heavier with more body fat during suckling. Metformin exposure decreased maternal glucose and several amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to recuse from the effects of a maternal HFD during lactation.
2021-06-04 | GSE176118 | GEO
Project description:The perinatal environment has been suggested to participate to the development of tauopathies and Alzheimer’s disease but the molecular and cellular mechanisms involved remain contradictory and under-investigated. Here, we evaluated the effects of a maternal high-fat diet (HFD) during lactation on the development of tauopathy in the THY-Tau22 mouse strain, a model of progressive tau pathology associated with cognitive decline. During lactation, dams were fed either a chow diet (13.6% of fat) or a HFD (58% of fat). At weaning, offspring was fed a chow diet until sacrifice at 4 months of age (the onset of tau pathology) or 7 months of age (the onset of cognitive impairment). During lactation, maternal HFD increased body weight gain in offspring. At 3 months of age, maternal HFD led to a mild glucose intolerance only in male offspring. Moreover, it impaired spatial memory in both male and female 6-month-old offspring, with males being more impacted. These cognitive deficits were associated with increased phosphorylation of hippocampal tau protein-observed at 4 months in males and at 7 months in females, highlighting a sex-specific temporal shift. Additionally, maternal HFD modified adult hippocampal neurogenesis (AHN), leading to an increase of mature neuronal cells number in females and of dendritic arborization length in males. Synaptic analysis further revealed that maternal HFD led to synaptic loss only in males. Finally, multi-omics approaches showed that maternal HFD has long-term consequences on both transcriptome, proteome and regulome, this effect being also sex-dependent with mitochondrial pathways, ribosomal activity, cilium and the extracellular matrix predominantly impacted in males, while gliogenesis, myelination and synaptic plasticity were primarily affected in females. Regulome analysis suggested that this sex-dependent phenotype was more related to a temporal shift rather than distinct sex-specific alterations. Collectively, our data suggest that maternal malnutrition accelerates the development of tauopathy in THY-Tau22 offspring, with sex-dependent effects, males being impacted earlier than females. These findings highlight the critical role of the perinatal environment as a key window of opportunity for interventions aimed at preventing the development of neurodegenerative diseases.
2026-09-18 | PXD063974 | Pride
Project description:Naïve CD4+ T cells coordinate the immune response by acquiring an effector phenotype in response to cytokines. However, the cytokine responses in memory T cells remain largely understudied. We used quantitative proteomics, bulk RNA-seq and single-cell RNA-seq of over 40,000 human naïve and memory CD4+ T cells to generate a detailed map of cytokine-regulated gene expression programs. We demonstrated that cytokine response differs substantially between naïve and memory T cells and showed that memory cells are unable to differentiate into the Th2 phenotype. Moreover, memory T cells acquire a Th17-like phenotype in response to iTreg polarization. At the single-cell level, we demonstrated that T cells form a continuum which progresses from naïve to effector memory T cells. This continuum is accompanied by a gradual increase in the expression levels of chemokines and cytokines and thus represents an effectorness gradient. Finally, we found that T cell cytokine responses are determined by where the cells lie in the effectorness gradient and identified genes whose expression is controlled by cytokines in an effectorness-dependent manner. Our results shed light on the heterogeneity of T cells and their responses to cytokines, provide insight into immune disease inflammation and could inform drug development.
2020-03-04 | PXD015315 | Pride
Project description:Deciphering the immune privilege of maternal-fetal interface is critical to understand how reproductive success and host defense are simultaneously maintained. Here, we identify a conserved subset of effector-like memory CD8⁺ T cells that are preferentially infiltrate in the decidua of both humans and mice, via the CX3CL1–CX3CR1 axis. Murine decidual CX3CR1⁺ memory CD8⁺ T cells and human decidual CX3CR1⁺ CD8⁺ T cells share transcriptional and functional programs, characterized by reduced cytokine output but enhanced cytotoxic granule production. We show that decidual stromal cells upregulate CX3CL1 during decidualization, which recruits CX3CR1⁺ cells via receptor engagement and internalization. Functionally, these cells mediate enhanced local protection against Listeria monocytogenes infection at the fetal-maternal interface in a CX3CL1-dependent manner, without contributing to fetal damage. These findings define a conserved mechanism by which decidual tissues selectively enrich effector-like memory CD8⁺ T cells, enabling localized pathogen surveillance while maintaining maternal–fetal tolerance.
2026-09-30 | GSE338652 | GEO