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Maternal vitamin D deficiency induces transcriptomic changes in newborn rat lungs
Erica Mandell1, Sharon Ryan1, Gregory J Seedorf1
1Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado, Denver Anschutz Medical Center, Aurora, CO, USA.
Insights
Maternal Vitamin D deficiency (VDD) during pregnancy alters fetal lung development, impacting airway, alveolar, and vascular growth. This study reveals VDD disrupts innate immune pathways and anabolic signaling, contributing to abnormal lung development.
Area of Science:
- Developmental Biology
- Immunology
- Genomics
Background:
- Vitamin D deficiency (VDD) in pregnancy is prevalent and linked to adverse maternal and fetal outcomes.
- Vitamin D (VD) is crucial for normal lung development, and VDD can lead to abnormal airway, alveolar, and vascular growth in neonates.
Purpose of the Study:
- To identify molecular pathways affected in the lungs of offspring exposed to maternal VDD using an unbiased transcriptomic approach.
Main Methods:
- RNA was extracted from the lungs of newborn offspring from VD-replete and VDD dams.
- Affymetrix microarrays were used for transcriptomic analysis.
- Differential gene expression and pathway enrichment analyses were performed.
Main Results:
- 2233 differentially expressed transcripts were identified between VDD and control offspring lungs.
- Suppressed pathways included vascular biology, insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), and cell cycle control.
- Upregulated pathways were predominantly related to the innate immune system, including granulocyte/macrophage development and cytokine signaling (Jak/Stat).
Conclusions:
- Maternal VDD during fetal development induces significant alterations in lung gene expression beyond angiogenic pathways.
- These transcriptomic changes are associated with abnormal lung growth and may create a proinflammatory environment contributing to impaired lung development.
Abstract:
Vitamin D deficiency (VDD) during pregnancy is common and related to several maternal and fetal morbidities. Vitamin D (VD) plays a role in normal lung development and VDD causes abnormal airway, alveolar, and vascular growth in newborn rats. Here we use an unbiased transcriptomic approach to identify pathways altered in the lungs of offspring from VDD dams. The lungs of newborn offspring from VD replete and VDD dams were removed and RNA from these samples were analyzed using Affymetrix microarrays. Data were RMA normalized, differential gene expression was determined using Significance Analysis of Microarrays (5 % FDR) and pathway enrichment analysis was assessed. There were 2233 differentially expressed transcripts between the VDD and control lungs (1889 up, 344 down). Consistent with the suppression of lung growth in the VDD group, there were significant suppression of signal transduction pathways related to vascular biology and anabolic signaling pathways, e.g. the insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), cell cycle control. A major, enriched functional category was upregulation of pathways related to the innate immune system, including pathways for granulocyte and macrophage development, chemotaxis, and activation of cytokine signaling through Jak/Stat (e.g. resulting in higher IL1 α and β). We conclude that VDD during fetal development alters multiple pathways beyond the predicted angiogeneic alterations. These changes either contribute to, or reflect, the abnormal airway, alveolar, and vascular growth seen in the neonatal lung resulting from maternal VDD. The pattern also suggests abnormal lung development caused by maternal VDD creates a proinflammatory milieu that could contribute to the suppression of lung growth and development.
