Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation

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Abstract

Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D-depleted diet. After 10 wk, nonsibling rats were mated. The conceived pups received standard chow. We observed an increased systolic and diastolic blood pressure in the offspring from depleted parents (F1-depl). Genome-wide methylation analyses in offspring identified hypermethylation of the promoter region of the Pannexin-1 (Panx1) gene in F1-depl rats. Panx1 encodes a hemichannel known to be involved in endothelial-dependent relaxation, and we demonstrated that in F1-depl rats the increase in blood pressure was associated with impaired endothelial relaxation of the large vessels, suggesting an underlying biological mechanism of increased blood pressure in children from parents with vitamin deficiency. Parental vitamin D deficiency is associated with epigenetic changes and increased blood pressure levels in offspring.

Original languageEnglish
Pages (from-to)H1459-H1469
Number of pages11
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume311
Issue number6
DOIs
Publication statusPublished - 1-Dec-2016

Keywords

  • Animals
  • Atrial Natriuretic Factor
  • Blood Pressure
  • Blotting, Western
  • Connexins
  • DNA Methylation
  • Endothelium, Vascular
  • Epigenesis, Genetic
  • Female
  • Hypertension
  • Male
  • Maternal Exposure
  • Nerve Tissue Proteins
  • Parathyroid Hormone
  • Paternal Exposure
  • Pregnancy
  • Pregnancy Complications
  • Prenatal Exposure Delayed Effects
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptor, Angiotensin, Type 1
  • Receptors, Calcitriol
  • Renin
  • Vasodilation
  • Vitamin D
  • Vitamin D Deficiency
  • Journal Article
  • Video-Audio Media
  • PLASMA-RENIN ACTIVITY
  • DNA-METHYLATION
  • DUTCH FAMINE
  • ENDOTHELIAL FUNCTION
  • RENAL-INSUFFICIENCY
  • CARDIOVASCULAR RISK
  • HEART-FAILURE
  • PANNEXIN 1
  • HYPERTENSION
  • ABNORMALITIES

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