# Neurogenesis decreases in the offspring of mothers infected with influenza A virus

## TL;DR

Maternal influenza infection during pregnancy reduces neurogenesis in offspring, potentially leading to long-term cognitive issues.

## Contribution

This study reveals how maternal H1N1 influenza infection disrupts hippocampal neurogenesis and triggers neuroinflammation in offspring.

## Key findings

- Maternal H1N1wsn infection disrupts early neurogenesis in neonatal offspring.
- H1N1pdm09 infection causes region-specific neurogenesis reduction and increased glial reactivity.
- Elevated pro-inflammatory cytokines suggest immune activation mediates neurodevelopmental disruptions.

## Abstract

Seasonal influenza virus infection during pregnancy poses significant risks to maternal and fetal health, contributing to adverse neurodevelopmental outcomes in offspring. This study investigates the impact of maternal infection with two highly pathogenic H1N1 influenza A virus (IAV) strains on hippocampal neurogenesis and glial reactivity in neonatal and juvenile mice.

Mice were infected with the mouse-adapted influenza virus strain A/WSN/33 (H1N1) or A/California/07/09 (H1N1)pdm09 in a sublethal dose 14 days after pregnancy manifestation. After birth, several pups were sacrificed, brains and hippocampi were isolated and used for RT-qPCR (the expression of IL-1β, iNOS, IFNG, IL-6, TNFa was assessed), immunohistochemistry and Western blot for markers of neural progenitors (Sox2, Sox11), mature neurons (NeuN), microglia (Iba1), and astrocytes (GFAP). Within 2 weeks after birth, the mortality and body weight dynamics change were monitored in the remaining pups.

Findings reveal that maternal infection with H1N1wsn disrupts early neurogenesis, while infection with H1N1pdm09 induces region-specific reductions in neurogenesis and heightened glial reactivity in 14-day-old offspring. Increased expression of pro-inflammatory cytokines and factors, including IL-1β and iNOS, in neonatal brain tissue suggests that maternal immune activation mediates neurodevelopmental disruptions. Despite reduced Sox2+ and Sox11+ neural progenitor cells, NeuN expression remained stable, implying potential compensatory mechanisms. Elevated astrocyte reactivity in the CA1 and dentate gyrus regions highlights prolonged neuroinflammatory effects. These results underscore the role of maternal influenza-induced immune responses in shaping hippocampal development, with implications for long-term cognitive and behavioral outcomes. Understanding these mechanisms may inform strategies to mitigate neurodevelopmental risks associated with prenatal infections.