Abstract
BACKGROUND: Pregnancy is a major modifier of vitamin D metabolism, which is suggested to serve an immunomodulatory role, support placental function, and aid fetal development. However, little is known about local tissue concentrations of vitamin D metabolites following supplementation during gestation. OBJECTIVES: We aimed to quantify intracellular concentrations of 25-hydroxyvitamin D(3) (25[OH]D) and the bioactive 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D) across tissues following vitamin D supplementation and to determine how this distribution is altered during gestation in mice. METHODS: Forty nulliparous female C57BL/6 (wild-type) mice were fed a semipurified diet supplemented with either a normal (1000 IU/kg) or high-dose (6000 IU/kg) vitamin D(3) (cholecalciferol) for 4 wk. Thirty females were mated with 10 diet-matched C57BL/6 males, whereas 10 females served as nonpregnant controls. Maternal serum, lung, liver, kidney, and placental tissue and fetal samples were collected at gestational day 18.5. Concentrations of 25(OH)D and 1,25(OH)(2)D were measured using high-pressure liquid chromatography and tandem mass spectrometry and compared between groups using t tests in R (R Foundation for Statistical Computing). RESULTS: High-dose vitamin D supplementation increased serum 25(OH)D (calcidiol) across all groups, with a clear dose response. Serum 1,25(OH)(2)D (calcitriol) concentrations were substantially increased in pregnant compared with nonpregnant females (mean difference: 74 pg/mL for control dose, P < 0.05 and 65 pg/mL for high dose, P = 0.1). Tissue analysis revealed the lungs as important targets of 25(OH)D accumulation, with significantly higher concentrations than liver tissue in nonpregnant (mean difference: 27 ng/g, P < 0.05) mice. Pregnancy induced notable shifts in vitamin D metabolite distribution, including reduced serum 25(OH)D concentrations and enhanced renal conversion to serum 1,25(OH)(2)D. Despite high placental accumulation of 25(OH)D, fetal 25(OH)D concentrations were significantly lower in the high-dose group (mean difference: -2.6 ng/g, P < 0.05), suggesting a protective saturation mechanism. High-dose vitamin D supplementation was well tolerated without any adverse gestational events. CONCLUSIONS: Our findings suggest that pregnancy results in a redistribution of vitamin D metabolites in tissues, with the kidneys and placenta playing central roles. This distribution is responsive to prenatal vitamin D supplementation; however, under supraphysiological maternal dosing, fetal 25(OH)D uptake may be decreased.