title: Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation.
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.
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Laura M G
authors: LM
authors: Meems
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Hasan
authors: H
authors: Mahmud
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Hendrik
authors: H
authors: Buikema
authors: Centre National de Génotypage, CEA-Institute de Génomique, Laboratory for Epigenetics and Environment, Evry, France.
authors: Jörg
authors: J
authors: Tost
authors: Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany; and.
authors: Sven
authors: S
authors: Michel
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Janny
authors: J
authors: Takens
authors: Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Rikst N
authors: RN
authors: Verkaik-Schakel
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Inge
authors: I
authors: Vreeswijk-Baudoin
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Irene V
authors: IV
authors: Mateo-Leach
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Pim
authors: P
authors: van der Harst
authors: Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Torsten
authors: T
authors: Plösch
authors: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; r.a.de.boer@umcg.nl.
authors: Rudolf A
authors: RA
authors: de Boer
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D015153:Blotting, Western; D017630:Connexins / Q000235:genetics*; D019175:DNA Methylation; D004730:Endothelium, Vascular / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D018811:Maternal Exposure; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010281:Parathyroid Hormone / Q000378:metabolism; D018812:Paternal Exposure; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D012083:Renin / Q000235:genetics; D014664:Vasodilation / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D018167:Receptors, Calcitriol; C479936:pannexin 1, rat; D014807:Vitamin D; D009320:Atrial Natriuretic Factor; C104450:25-hydroxyvitamin D; D012083:Renin
keywords: Pannexin-1; blood pressure; endothelial dysfunction; epigenetics; vitamin D