Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring

PLoS One. 2016 Aug 29;11(8):e0155203. doi: 10.1371/journal.pone.0155203. eCollection 2016.

Abstract

Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL) or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OH)D) determinations. After cesarean section at gestational day 19 (E19) or day 22 (E22), placental weight, birth weight, crown-rump-length (CRL), oxygenation (SaO2) at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR). S-25(OH)D was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p<0.0001). Compared to the controls, E19 VDL pups had lower birth weight (2.13 vs. 2.29g, p<0.001), lung weight (0.09 vs. 0.10g, p = 0.002), SaO2 (54% vs. 69%, p = 0.002) as well as reduced survival time (0.50 vs. 1.25h, p<0.0001). At E22, the VDL-induced pulmonary differences were leveled out, but VDL pups had lower CRL (4.0 vs. 4.5cm, p<0.0001). The phospholipid levels and the surfactant protein mRNA expression did not differ between the dietary groups. In conclusion, Vitamin D depletion led to lower oxygenation and reduced survival time in the preterm offspring, associated with reduced lung weight and birth weight. Further studies of vitamin D depletion in respiratory insufficiency in preterm neonates are warranted.

MeSH terms

  • Animals
  • Body Weight / physiology
  • Female
  • Lung / metabolism*
  • Lung / physiology*
  • Male
  • Organ Size / physiology*
  • Oxygen / metabolism*
  • Pregnancy
  • Premature Birth / blood*
  • Premature Birth / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood*
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / physiopathology*

Substances

  • Vitamin D
  • 25-hydroxyvitamin D
  • Oxygen

Grants and funding

All studies were financially supported by: Dagmar Marshalls foundation, Aase & Ejner Danielsens foundation, Takeda Pharma, The A.P. Moeller Foundation for the Advancement of Medical Science and Odense University Hospital. The funding sources had no involvement in collection, analysis and interpretation of data, writing of the report, or decision to submit the article for publication.