Pre- and Postnatal Vitamin A Deficiency Impairs Motor Skills without a Consistent Effect on Trace Mineral Status in Young Mice

Abstract

Pregnant women and children are vulnerable to vitamin A deficiency (VAD), which is often compounded by concurrent deficiencies in other micronutrients, particularly iron and zinc, in developing countries. The study investigated the effects of early-life VAD on motor and cognitive development and trace mineral status in a mouse model. C57BL/6J dams were fed either a vitamin A-adequate (VR) or -deficient (VD) diet across two consecutive gestations and lactations. Offspring from both gestations (G1 and G2) continued the same diets until 6 or 9 weeks of age. Behavioral assays were conducted to evaluate motor coordination, grip strength, spatial cognition, and anxiety. Hepatic trace minerals were analyzed. A VD diet depleted hepatic retinoids and reduced plasma retinol across all ages and gestations. Retracted rear legs and abnormal gait were the most common clinical manifestations observed in VD offspring from both gestations at 9 weeks. Poor performance on the Rotarod test further confirmed their motor dysfunction. VAD didn't affect hemoglobin levels and had no consistent effect on hepatic trace mineral concentrations. These findings highlight the critical role of vitamin A in motor development. There was no clear evidence that VAD alters the risk of iron deficiency anemia or trace minerals.

Keywords: concurrent micronutrient deficiencies; growth retardation; maternal vitamin A deficiency; motor dysfunction; mouse model.

Figure 1

Effect of early-life vitamin A deficiency on growth and development of mouse offspring. The postweaning body weight change (A), body weight (B), brain weight (C), brain-to-body weight ratio (D), intestinal length (E), and tail length (F) of 9-week-old offspring born from the first gestation (G1, n = 6–12 mice/(sex∙treatment)). Figures (G–L) show the corresponding growth parameters of 6-week-old offspring born from the second gestation (G2, n = 6–10 mice/(sex∙treatment)), respectively. Figures (M–R) show the corresponding growth parameters of 9-week-old offspring born from the G2 (n = 6–9 mice/treatment), respectively. VR, vitamin A-adequate diet; VD, vitamin A-free diet. Data present LS means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 2

Effect of early-life vitamin A deficiency on blood hemoglobin concentration. Figures (A–C) show the hemoglobin concentrations in 9-week-old offspring born from the first gestation (G1, n = 7–12 mice/(sex∙treatment)) and 6-week (n = 6–10 mice/(sex∙treatment)) and 9-week-old offspring (n = 6–9 mice/treatment) born from the second gestation (G2), respectively. VR, vitamin A-adequate diet; VD, vitamin A-free diet. Data present LS means ± SEM.

Figure 3

Effect of early-life vitamin A deficiency on hepatic trace mineral concentrations. Figures (A–E) show hepatic trace mineral concentrations in 9-week-old offspring born from the first gestation (G1, n = 7–12 mice/(sex∙treatment)). Figures (F–J) and figures (K–O) show hepatic trace mineral concentrations in 6-week-old (n = 6–10 mice/(sex∙treatment)) and 9-week-old (n = 6–9 mice/treatment) offspring born from the second gestation (G2), respectively. VR, vitamin A-adequate diet; VD, vitamin A-free diet. Data present LS means ± SEM. ** p < 0.01, and *** p < 0.001.

Figure 4

Effect of early-life vitamin A deficiency on motor function assessed through Rotarod test. Rotarod test performance of 9-week-old offspring born from the first gestation (G1, n = 5 mice/treatment) was assessed based on the highest speed of rotation (A), travel distance (B), and travel duration (C). Figures (D–F) and figure (G–I) show corresponding test parameters for 6- (n = 5–6/treatment) and 9-week-old (n = 6–8 mice/treatment) offspring born from the second gestation (G2), respectively. VR, vitamin A-adequate diet; VD, vitamin A-free diet. Data present LS means ± SEM. ** p < 0.01, *** p < 0.001, and **** p < 0.0001.