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Prenatal Glucocorticoid Exposure Disrupts a Subcluster Microglia Maturation Leading to ASD-like Behavior

ABSTRACT: Prenatal glucocorticoid exposure, whether due to pharmacological treatment or stress-induced maternal overproduction, has been associated with an increased risk of autism spectrum disorders (ASD), yet the underlying neurodevelopmental mechanisms remain poorly understood. Here, we report that late-pregnancy exposure to dexamethasone resulted in ASD-like behaviors in adolescent offsprings, accompanied by an increased density of immature dendritic spines and imbalance of neurotransmission in hippocampus. Single-cell RNA sequencing uncovered a significant expansion of MRC1+ microglia derived from border-associated macrophages (BAM) following prenatal exposure, with arrested maturation into homeostatic microglia. Strikingly, this population exhibited selective F13a1 upregulation. Early postnatal inhibition of F13A1 restored microglial maturation and ameliorated behavioral abnormalities and dendritic spine deficits. Elevated levels of F13A1 were also observed in the plasma of postnatal rats and in the umbilical cord blood of human females exposed to prenatal glucocorticoids, suggesting its potential value as a biomarker.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE301147 | GEO | 2025/12/03

REPOSITORIES: GEO

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