Maternal gestational iron deficiency is associated with behavioral alterations and reduced brain iron concentrations in rat offspring

Maternal iron deficiency during gestation may have long-lasting effects on offspring neurodevelopment; however, the relationships between behavioral alterations, iron homeostasis, and neurobiological outcomes remain incompletely understood. This study investigated neurobehavioral and neurobiological alterations in offspring rats exposed to maternal gestational iron deficiency despite postnatal nutritional recovery. Female Wistar Kyoto rats were administered either a control or iron-deficient diet throughout gestation, whereas spontaneously hypertensive rats (SHR) served as a phenotypic reference group. Postpartum, all dams and offspring received a standard diet. Behavioral performance was assessed during adolescence using open field, Y-maze, and elevated plus maze tests. Serum iron status, brain and liver iron concentrations, hippocampal brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) protein expression were also evaluated. Maternal gestational iron deficiency was associated with alterations in multiple behavioral outcomes. Offspring exposed to maternal iron deficiency exhibited reduced serum iron concentrations, altered unsaturated iron-binding capacity, and lower brain iron concentrations, whereas liver iron concentrations remained unchanged. Hippocampal BDNF expression was altered in a sex-dependent manner, whereas full-length TrkB expression was unaffected. Several outcomes exhibited sex-dependent patterns. Overall, maternal gestational iron deficiency was associated with persistent neurobehavioral and neurobiological alterations despite postnatal nutritional recovery. These findings suggest that maternal iron availability during gestation may have lasting implications for offspring neurodevelopment and underscore the significance of adequate maternal iron availability during gestation.