Microglia alter sex-specific cerebellar myelination following placental hormone loss.

ABSTRACT: Placental dysfunction is linked to neurodevelopmental disorders, with males showing greater vulnerability to perinatal inflammation-mediated brain injuries. Using our transgenic mouse model, Akr1c14^cyp19aKO (plKO), we investigate how reduced placental allopregnanolone (ALLO), an anti-inflammatory neurosteroid, contributes to sex-specific brain injury. plKO mice display sex-divergent cerebellar myelination and male-specific autism-like behaviors. Here we show that placental ALLO insufficiency triggers sex-divergent neuroinflammatory responses and microglial dysfunction. Sex-divergent differential expression of inflammatory genes and distinct inflammatory cytokine/chemokine patterns are seen in the placenta and the brain. Prostaglandin E2 (PGE2)-EP4 signaling is identified as a ke

SUBMITTER: Salzbank J 

PROVIDER: S-EPMC12594813 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature