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Vitamin D supplementation blocks pulmonary structural and functional changes in a rat model of perinatal vitamin D
Methap Yurt1, Jie Liu1, Reiko Sakurai1
1Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
Insights
Perinatal vitamin D (VD) deficiency increases childhood asthma risk by affecting airway contractility. Supplementing pregnant rats with 500 IU/kg VD prevented these adverse effects, suggesting a preventive strategy for asthma.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Nutritional Science
Background:
- Epidemiological studies link vitamin D deficiency to childhood asthma.
- The molecular mechanisms and protective effects of perinatal vitamin D supplementation against asthma remain unclear.
- Vitamin D influences perinatal lung maturation via epithelial-mesenchymal interactions.
Purpose of the Study:
- To investigate the effects of perinatal vitamin D deficiency on pulmonary function and airway contractility in an in vivo rat model.
- To determine the efficacy of different doses of cholecalciferol supplementation in preventing these effects.
- To provide insights into the pathogenesis of asthma in vitamin D-deficient offspring.
Main Methods:
- Rat dams were fed diets with varying cholecalciferol (vitamin D) levels (0, 250, 500, 1000 IU/kg) before and during pregnancy and lactation.
- Offspring pulmonary function was assessed using whole-body plethysmography and tracheal contraction response to acetylcholine.
- Plasma 25(OH)D levels were measured in offspring at postnatal day 21.
Main Results:
- Perinatal vitamin D deficiency significantly increased airway resistance and tracheal contractility in offspring.
- The negative effects on airway function were dose-dependently mitigated by cholecalciferol supplementation.
- Supplementation with 500 IU/kg cholecalciferol effectively blocked the deficiency-induced increase in tracheal contractility.
Conclusions:
- Perinatal vitamin D deficiency adversely affects offspring airway contractility, contributing to asthma pathogenesis.
- Perinatal vitamin D supplementation, particularly at 500 IU/kg, can prevent these detrimental effects in a rat model.
- These findings support a clinical rationale for effective perinatal vitamin D supplementation to prevent childhood asthma.
Abstract:
Whereas epidemiological data strongly link vitamin D (VD) deficiency to childhood asthma, the underlying molecular mechanisms remain unknown. Although VD is known to stimulate alveolar epithelial-mesenchymal interactions, promoting perinatal lung maturation, whether VD supplementation during this period protects against childhood asthma has not been demonstrated experimentally. Using an in vivo rat model, we determined the effects of perinatal VD deficiency on overall pulmonary function and the tracheal contraction as a functional marker of airway contractility. One month before pregnancy, rat dams were put on either a no cholecalciferol-added or a 250, 500, or 1,000 IU/kg cholecalciferol-added diet, which was continued throughout pregnancy and lactation. At postnatal day 21, offspring plasma 25(OH)D levels and pulmonary function (whole body plethysmography and tracheal contraction response to acetylcholine) were determined. 25(OH)D levels were lowest in the no cholecalciferol-supplemented group, increasing incrementally in response to cholecalciferol supplementation. Compared with the 250 and 500 IU/kg VD-supplemented groups, the no cholecalciferol-supplemented group demonstrated a significant increase in airway resistance following methacholine challenge. However, the cholecalciferol deficiency-mediated increase in tracheal contractility in the cholecalciferol-depleted group was only blocked by supplementation with 500 IU/kg cholecalciferol. Therefore, in addition to altering alveolar epithelial-mesenchymal signaling, perinatal VD deficiency also alters airway contractility, providing novel insights to asthma pathogenesis in perinatally VD-deficient offspring. Perinatal VD supplementation at 500 IU/kg appears to effectively block these effects of perinatal VD deficiency in the rat model used, providing a strong clinical rationale for effective perinatal VD supplementation for preventing childhood asthma.
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