Related Experiment Video
Updated: Jul 28, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Prenatal vitamin D supplementation mitigates inflammation-related alveolar remodeling in neonatal mice
Julia Waiden1, Motaharehsadat Heydarian1, Prajakta Oak1
1Institute for Lung Health and Immunity and Comprehensive Pneumology Center, Helmholtz Zentrum München, German Center for Lung Research (DZL), Munich, Germany.
Insights
Prenatal vitamin D supplementation reduced lung inflammation and tissue remodeling in newborn mice exposed to injury. This suggests preventing vitamin D deficiency during pregnancy may improve offspring lung health.
Area of Science:
- Neonatology
- Pulmonology
- Developmental Biology
Background:
- Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants.
- Postnatal treatments like mechanical ventilation and oxygen can exacerbate lung injury and remodeling in BPD.
- Prenatal factors may influence lung vulnerability to postnatal injury.
Purpose of the Study:
- To investigate the impact of prenatal vitamin D status on neonatal lung injury and inflammation.
- To evaluate if prenatal vitamin D supplementation can mitigate lung damage and remodeling in a preclinical model.
Main Methods:
- A mouse model was used, administering vitamin D-enriched or -deprived diets to pregnant dams.
- Neonatal mice were exposed to hyperoxia with or without mechanical ventilation.
- Lung inflammation, TGF-β pathway activation, and extracellular matrix remodeling were assessed.
Main Results:
- Prenatal vitamin D supplementation decreased inflammatory cells (monocytes/macrophages) and TGF-β activation in the neonatal lung.
- Mice with prenatal vitamin D enrichment showed reduced extracellular matrix remodeling, including less collagen and elastin deposition.
- Pulmonary α-smooth muscle actin-positive fibroblasts and interstitial tissue were also reduced.
Conclusions:
- Prenatal vitamin D sufficiency may protect the developing lung from postnatal injury and subsequent remodeling.
- Preventing vitamin D insufficiency during pregnancy could be a strategy to improve infant lung health.
- Monitoring subclinical vitamin D insufficiency is important for offspring health outcomes.
Abstract:
The development of chronic lung disease in the neonate, also known as bronchopulmonary dysplasia (BPD), is the most common long-term complication in prematurely born infants. In BPD, the disease-characteristic inflammatory response culminates in nonreversible remodeling of the developing gas exchange area, provoked by the impact of postnatal treatments such as mechanical ventilation (MV) and oxygen treatment. To evaluate the potential of prenatal treatment regimens to modulate this inflammatory response and thereby impact the vulnerability of the lung toward postnatal injury, we designed a multilayered preclinical mouse model. After administration of either prenatal vitamin D-enriched (VitD+; 1,500 IU/g food) or -deprived (VitD-; <10 IU/kg) food during gestation in C57B6 mice (the onset of mating until birth), neonatal mice were exposed to hyperoxia (FiO = 0.4) with or without MV for 8 h at days 5-7 of life, whereas controls spontaneously breathed room air. Prenatal vitamin D supplementation resulted in a decreased number of monocytes/macrophages in the neonatal lung undergoing postnatal injury together with reduced TGF-β pathway activation. In consequence, neonatal mice that received a VitD+ diet during gestation demonstrated less extracellular matrix (ECM) remodeling upon lung injury, reflected by the reduction of pulmonary α-smooth muscle actin-positive fibroblasts, decreased collagen and elastin deposition, and lower amounts of interstitial tissue in the lung periphery. In conclusion, our findings support strategies that attempt to prevent vitamin D insufficiency during pregnancy as they could impact lung health in the offspring by mitigating inflammatory changes in neonatal lung injury and ameliorating subsequent remodeling of the developing gas exchange area.NEW & NOTEWORTHY Vitamin D-enriched diet during gestation resulted in reduced lung inflammation and matrix remodeling in neonatal mice exposed to clinically relevant, postnatal injury. The results underscore the need to monitor the subclinical effects of vitamin D insufficiency that impact health in the offspring when other risk factors come into play.
