Maternal vitamin D deficiency causes smaller muscle fibers and altered transcript levels of genes involved in protein degradation, myogenesis, and cytoskeleton organization in the newborn rat.

SCOPE Epidemiologic data reveal associations between low serum concentrations of 25-hydroxyvitamin D (25(OH)D) and higher risk of falls and muscle weakness. Fetal stage is critical for the development of skeletal muscle, but little information is available on the impact of maternal vitamin D deficiency on muscles of offspring. METHODS AND RESULTS To investigate the morphology and transcriptome of gastrocnemius muscle in newborns in response to maternal vitamin D deficiency, 14 female rats were fed either a vitamin D₃ deficient (0 IU/kg) or a vitamin D₃ adequate diet (1000 IU/kg) 8 weeks prior to conception, during pregnancy, and lactation. Analysis of cholecalciferol, 25(OH)D₃ and 1,25-dihydroxyvitamin D₃ show that dams fed the vitamin D deficient diet and their newborns suffered from a relevant vitamin D deficiency. Muscle cells of vitamin D deficient newborns were smaller than those of vitamin D adequate newborns (p < 0.05). Muscle transcriptome of the newborns revealed 426 probe sets as differentially expressed (259 upregulated, 167 downregulated) in response to vitamin D deficiency (fold change ≥1.5, p < 0.05). The effected genes are involved in protein catabolism, cell differentiation and proliferation, muscle cell development, and cytoskeleton organization. CONCLUSION Maternal vitamin D deficiency has a major impact on morphology and gene expression profile of skeletal muscle in newborns.