Gestational vitamin D deficiency impairs fetal lung development through suppressing type II pneumocyte differentiation

Reprod Toxicol. 2020 Jun:94:40-47. doi: 10.1016/j.reprotox.2020.03.008. Epub 2020 Apr 21.

Abstract

Gestational vitamin D deficiency is associated with pulmonary diseases. This study aimed to investigate the effect of gestational vitamin D deficiency on fetal lung development in mice. Absolute and relative weights of fetal lungs were reduced in vitamin D deficient (VDD) group. Incrassate mesenchyme, measured by septal wall thickness, accompanied by lessened saccular space, was shown in VDD group. Numerous immature type II pneumocytes, as determined by PAS staining, were observed in VDD group. Moreover, increased Ki67-positive cells, a marker of cell proliferation, was detected in VDD group. The additional experiments showed that Sftpa, Sftpb, Sftpc and Sftpd, four surfactant genes, were downregulated and pro-surfactant protein B was reduced in VDD group. FoxA1, FoxA2 and TTF-1, three transcription factors that regulate surfactant genes, and VEGF, a key regulator for pulmonary maturation, were downregulated in VDD group. These results suggest that gestational vitamin D deficiency impairs fetal lung development partially through suppressing type II pneumocyte differentiation.

Keywords: Fetus; Lung development; Pregnancy; Vitamin D deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / cytology*
  • Alveolar Epithelial Cells / metabolism
  • Animals
  • Cell Differentiation
  • Cytokines / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Fetal Development*
  • Fetus
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Humans
  • Ki-67 Antigen / metabolism
  • Lung / growth & development*
  • Male
  • Mice
  • Pregnancy
  • Pulmonary Surfactant-Associated Proteins / genetics
  • Pulmonary Surfactant-Associated Proteins / metabolism
  • Transcription Factors / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / metabolism
  • Vitamins / blood

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Foxa1 protein, mouse
  • Foxa2 protein, mouse
  • Hepatocyte Nuclear Factor 3-alpha
  • Ki-67 Antigen
  • Pulmonary Surfactant-Associated Proteins
  • Transcription Factors
  • Ttf1 protein, mouse
  • Vascular Endothelial Growth Factor A
  • Vitamins
  • vascular endothelial growth factor A, mouse
  • Hepatocyte Nuclear Factor 3-beta
  • Vitamin D