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Fetal brain response to maternal inflammation requires microglia [Developing_Microglia]

ABSTRACT: In utero infection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal central nervous system infection, is associated with an increased risk of autism and schizophrenia in affected offspring. The cell types mediating the response of the fetal brain to maternal inflammation are largely unknown, hindering the development of therapies to prevent and treat adverse neuropsychiatric outcomes. Here, we show that microglia are enriched for expression of receptors for relevant pathogens and cytokines throughout embryonic development.

ORGANISM(S): Mus musculus

PROVIDER: GSE225464 | GEO | 2024/05/07

REPOSITORIES: GEO

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Project description:Activation of the maternal immune system during pregnancy can fetal development, which can lead to postnatal susceptibility to a wide range of diseases, including cardiovascular, metabolic and psychiatric disorders. During maternal immune activation (MIA), the maternal body must balance its ressources between mounting an immune response and investing resources into continued metabolism and growth : both essential for survival of the fetus and a successful pregnancy. How the placenta responds to MIA over time and how it can protect the fetus is not well understood, and neither are the fetal consequences of MIA. Here, we characterised the response to an induced acute inflammation in maternal lungs over time across maternal and fetal organs, using a combination of omics-methods, imaging and integrative computational analysis. We found that the placenta, unlike other maternal organs, did not react by inducing a typical inflammatory response, but instead initially induced genes associated to strengthen tissue integrity and simultaneously reduced growth to prevent exposure to potential infections. Afterwards, a return to homeostasis was observed, with heightened biosynthesis and expression of endoplasmic reticulum (ER) stress genes. This mechanism likely protects the fetus from inflammation, as we observed no immune response in the fetal liver transcriptome. Instead, we observed metabolic adaptations in the fetus, including a release of docosahexaenoic acid (DHA) Notably, DHA has a crucial function for fetal brain development , and levels of triglyceride and phosphatidylcholine lipids that are necessary for transportation of DHA to the brain were also increased. This metabolic response is likely a combination of the placental MIA response and temporary maternal fasting, caused by MIA-induced fever and lack of nutrient intake. Our study shows, for the first time, the temporal and systemic response to MIA in lungs across maternal and fetal organs.