Abstract

Prenatal glucocorticoid exposure is associated with higher risks of autism spectrum disorder (ASD), yet the underlying mechanisms remain poorly understood. Here, we report that late-pregnancy exposure to dexamethasone (a synthetic glucocorticoid) induces social memory deficiency and increased repetitive behaviors in offspring with an imbalance of neurotransmission in the hippocampus. Single-cell RNA sequencing uncovers an expansion of MRC1 + microglia, with arrested maturation. Strikingly, this population exhibits selective F13a1 (encoding a coagulation factor functioning as transglutaminase) upregulation. Early postnatal inhibition of F13A1 restores microglial maturation and ameliorates behavioral abnormalities. An elevated level of F13A1 is also observed in the plasma of postnatal rats and human umbilical cord blood exposed to prenatal glucocorticoids. Together, it suggests that prenatal glucocorticoid exposure disrupts the maturation of MRC1 + microglia, thereby causing social memory impairment and increased repetitive behaviors. This underscores that arrested maturation within a cluster of microglia may be related to ASD and identifies F13A1 as a promising therapeutic target and biomarker.