Effects Of Gestational Vitamin D Deficiency On Type ? Pneumocyte Maturation And Fetal Lung Development

Background and Objectives Whereas several of population-based surveys have demonstrated that gestational absence of vitamin D was correlated to poor lung development in offspring,it remained ambiguous how vitamin D functioned in lung development.The purpose of this survey intends to examine impacts of gestational vitamin D deficiency on fetal lung development how vitamin D worked.Methods Eight-week-old ICR females were randomly divided into control group(Control)and vitamin D deficiency group(VDD)according to body weight.Then,the mice were mated and the day of the vaginal plug was noted with GD 0.On GD 18,the pregnant rats were euthanized,the maternal blood was collected and the number of dead fetuses,absorbed fetus and the implantation site were recorded,and the weight of the fetus as well as lungs were weighed.Vitamin D deficient(VDD)diets(without any supplement of vitamin D3)were provided for mice to form an animal model of vitamin D deficiency.Serum 25(OH)D concentration was tested and weights of fetal lungs were recorded.Morphological and histological analysis was performed in fetal lung tissues via assessment on septal wall thickness and saccular space.Furthermore,we estimated the proliferation and differentiation of type II pneumocyte in fetal lungs,using Ki67and PAS staining,respectively.To confirm the changes of surfactant proteins homeostasis,we investigated the mRNA levels of Sftpa,Sftpb,Sftpc and Sftpd.Levels of Foxa1,Foxa2 and TTF-1,controlling synthesis of surfactant proteins were tested.Expressions of vascular endothelial growth factor a(Vegfa),as a target gene of VDR as well as a crucial role in the fetal lung maturation were detected.Results The results showed that the total 25(OH)D levels of the mice in the VDD diet-deficient group was significantly lower than that in the standard diet group,and thus the animal model of vitamin D deficiency during pregnancy was successfully established.In addition,the number of the implantation site in the VDD group was significantly lower than that in the Control group,and the number of dead fetuses per litter was significantly higher than that in the Control group.However,there was no significant difference in the number of abortions and resorptions between VDD and Control groups.As predicted,absolute and relative weights of fetal lungs were decreased in mice sustaining VDD diet.An incrassate mesenchyme,measured by septal wall thickness,accompanied with saccular space,was shown in fetal lungs of VDD mice.Moreover,increased Ki67-positive nuclei and PAS~+cells,were observed in VDD fetal lungs.Additional experiment showed that Sftpa,Sftpb,Sftpc and Sftpd,four surfactant genes,were downregulated and pro–surfactant protein B was reduced in fetal lungs of mice fed with VDD diets.The mRNAs of Foxa1,Foxa2 and TTF-1,and VEGF were downregulated in VDD fetal lungs.Conclusion:These findings indicate that gestational vitamin D deficiency impairs fetal lung development partially through suppressing type II pneumocyte maturation.