ArticleProceedings of the National Academy of Sciences of the United States of America2021
Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- The association between maternal immune activation and brain structure and function in human offspring: a systematic review.Molecular psychiatry · 2025Pooled it
- An epigenome-wide study of a needs-based family intervention for offspring of trauma-exposed mothers in Kosovo.Brain and behavior · 2024Trial
- Maternal Stress During Pregnancy Induces Higher Anxiety-Like Behavior in Male Mice Offspring Under Acute Stress by Upregulating CRF/CRFR1 and Driving Time-Specific Activation of the MHb-IPN Circuit.Neuroscience bulletin · 2026Article
- Prenatal stress alters offspring neurovascular, autonomic, and immune development in animal models of neuropsychiatric and cardiometabolic disorders.Journal of neuroendocrinology · 2026Review
- Exploring offspring behaviour after prenatal COVID-19 vaccination in mice.Translational psychiatry · 2026Article
- Ventromedial hypothalamus IL-6 signaling mediates the excessive aggressive behavior induced by late-gestational sleep deprivation in male mice.Behavioral and brain functions : BBF · 2026Article
- Impacts of prenatal resiquimod exposure during late gestation on rat offspring development and behavior.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Persistent priming of hypothalamic microglia is associated with sensitization of the hypothalamic-pituitary-adrenal axis to acute stress, hyperactivity and behavioral response disruption in male rats.Frontiers in immunology · 2026Article
- LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model.International journal of molecular sciences · 2025Article
- Tau Hypophosphorylation at Ser416 as the Early Molecular Imprint of Maternal Immune Activation: Insights from Female Mice Offspring.International journal of molecular sciences · 2025Article
- Decreased hippocampal neurite density in late-middle-aged adults following prenatal exposure to higher levels of maternal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Associations of lifetime stressors and health behaviors with inflammation in young adults previously placed in youth residential care.Brain, behavior, & immunity - health · 2025Article
- The Association of Preterm Birth With Autism Spectrum Disorder.Biological psychiatry global open science · 2025Article
- Decreased hippocampal neurite density in late middle-aged adults following prenatal exposure to higher levels of maternal inflammation.bioRxiv : the preprint server for biology · 2025Article
- Maternal Immune Activation and Child Brain Development: A Longitudinal Population-Based Multimodal Neuroimaging Study.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Article
- Sex-dependent biobehavioural responses to transgenerational maternal stress: evidence of stress resilience and vulnerability in the F3 generation.Environmental epigenetics · 2025Article
- Immune Alterations in the Intrauterine Environment Shape Offspring Brain Development in a Sex-Specific Manner.Biological psychiatry · 2025Review
- Maternal immune activation by toll-like receptor 7 agonist during mid-gestation increases susceptibility to blood-brain barrier leakage after puberty.Brain behavior and immunity integrative · 2024Article
- Acute Stress Increases Striatal Connectivity With Cortical Regions Enriched for μ and κ Opioid Receptors.Biological psychiatry · 2024Article
- Maternal immune activation with toll-like receptor 7 agonist during mid-gestation alters juvenile and adult developmental milestones and behavior.Journal of neuroendocrinology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 2 countries.
Funding
Abstract
Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring's risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.