(P11-004-23) Developmental Consequences of Concurrent Vitamin A and Iron Deficiency: Insight From a Murine Model

Objectives: The study investigates the effects of concurrent vitamin A and iron deficiency on growth and neurocognitive development in a mouse model.

Methods: Vitamin A-deficient (VDID) or replete (VRID), low-iron (30% of recommendation) AIN-93G diets were provided to breeding dams through gestation and lactation. Two litters of pups were generated from the same dam, the first litter of pups (G1) continued the same diet as their dams until 9 weeks of age while the second litter (G2) was fed the diet for 6 or 9 weeks of age. Water and feed were provided ad libitum and mice were weaned after 3 weeks and weighed weekly for growth measurements and at necropsy. G1 and G2 mice were evaluated for anxiety (Elevated Plus Maze), motor coordination (Rotarod), and grip strength (2 & 4 arms) at 6 weeks (G2) and 9 weeks (G1 & G2) of age. Tissue and blood samples were analyzed for vitamin A and iron status. Data were analyzed using the unpaired T-test, and two-and three-way ANOVA.

Results: Preliminary analysis shows that plasma retinol levels differed between VRID and VDID groups and clinical symptoms arose in G1(8.3% developed cataracts & 5.5% developed microphthalmia) and G2 (6.6% developed microphthalmia) at 9 weeks of age. For the G1 mice, the VDID group (N=17) had a shorter tail length (P < 0.0001), lower body weight (P < 0.0001), shorter intestinal length (P < 0.001), and lower brain weight (P < 0.001) compared to the VRID group (N=19). The 6 (N=19) and 9 (N=9) week G2 VDID mice had lower body weight (P < 0.0001) but similar intestinal and tail length, and brain weight compared to the 6 (N=14) and 9 (N=6) week VRID group. Pre-and postnatal vitamin A deficiency did not affect hemoglobin in G1 or G2 mice, nor did it affect anxious behaviors or 2-or 4-arm grip strength. Vitamin A deficiency was associated with poorer performance on the Rotarod test in G1 and G2 mice at 9 weeks (P < 0.0001) compared to the VRID group, suggesting impaired motor coordination.

Conclusions: Early-life exposure to the vitamin A deficient, low iron diet resulted in growth retardation and impaired motor function in the mouse model. Whether vitamin A deficiency altered iron metabolism will be determined later.

Funding Sources: Funding for this study was provided by NIFA Hatch-Multistate funding.