Morphological analysis of the hippocampus in rats exposed to Zika virus on embryonic day 9: Evidence of male vulnerability.

BACKGROUND: Congenital Zika syndrome (CZS) encompasses severe neurodevelopmental anomalies, however the impact of infection during early gestation - a critical window for neural tube closure - remains poorly understood. This study investigated some acute effects of Zika virus (ZIKV) inoculation during early gestation (gestational day 9, G9) on the hippocampus of neonate rats (postnatal day 1, PND1), focusing on volumetric changes and microglial morphology with emphasis on sex-specific differences. METHODS: Pregnant Wistar rats were intraperitoneally injected with ZIKV (1×106 PFU) or vehicle control, and offspring brains were analyzed using stereology for total encephalic, hippocampal, and dentate gyrus (DG) volumes, alongside immunofluorescence for IBA1-positive microglia in CA1, CA3, and DG subregions. RESULTS: Results revealed sexually dimorphic impact: male pup rats had hippocampal atrophy without affecting DG or total brain volume, accompanied by microglial simplification (reduced branches, junctions, and endpoints) in CA1 and CA3, indicative of neuroinflammation. In contrast, females showed no volumetric or morphological alterations. CONCLUSIONS: These findings highlight male vulnerability to ZIKV-induced early neurodevelopmental damage, underscoring sex as a key variable in Congenital Zika Syndrome pathogenesis and suggesting protective mechanisms in females, such as modulated microglial responses.