title: Vitamin D depletion does not affect key aspects of the preeclamptic phenotype in a transgenic rodent model for preeclampsia.
abstract: Maternal vitamin D deficiency is proposed as a risk factor for preeclampsia in humans. We tested the hypothesis that vitamin D depletion aggravates and high supplementation ameliorates the preeclampsia phenotype in an established transgenic rat model of human renin-angiotensin system-mediated preeclampsia. Adult rat dams, transgenic for human angiotensinogen (hAGT) and mated with male rats transgenic for human renin (hREN), were fed either vitamin D-depleted chow (VDd) or enriched chow (VDh) 2 weeks before mating and during pregnancy. Mean blood pressure was recorded by tail-cuff, and 24-hour urine samples were collected in metabolic cages at days 6 and 18 of gestation. Rats were sacrificed at day 21 of gestation. Depleted dams (VDd) had negligible serum 25-hydroxyvitamin D2+3 levels (mean ± SEM; 2.95 ± 0.45 nmol/l vs. VDh 26.20 ± 2.88 nmol/l, P = .01), but in both groups, levels of 1,25(OH)2D3 remained below detection level of 25 pmol/l. Dietary vitamin D depletion did not aggravate hypertension (mean ± SEM BP, day 20 of gestation: 151.38 ± 5.65 mmHg VDd vs. 152.00 ± 4.10 mmHg VDh) or proteinuria. Fetal anthropometrics were similar between the groups, whereas VDd displayed lower placental:fetal weight ratios (0.15 vs. 0.16 g/g, P = .01) and increased sFlt-1/PlGF ratio. Expression of hREN was lower in placenta of VDd dams (0.82 ± 0.44 AU vs. 1.52 ± 0.15 AU, P = .04). Expression of key vitamin D metabolizing enzymes was unchanged. Dietary vitamin D intervention did not alter key aspects of the preeclampsia phenotype using the transgenic rodent model of human renin-angiotensin system-mediated pre-eclampsia, plausibly due to altered vitamin D metabolism or excretion in the transgenic rats.
authors.affiliation: HansChristian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Louise Bjørkholt
authors.initials: LB
authors.lastname: Andersen
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitäsmedizin Berlin, Berlin, Germany; Department of Obstetrics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Gynecology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Golic
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitäsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Charité-Universitätsmedizin Berlin, Campus Berlin Buch, Berlin, Germany.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Przybyl
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Grith Lykke
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
authors.forename: Jan Stener
authors.initials: JS
authors.lastname: Jørgensen
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Palle
authors.initials: P
authors.lastname: Fruekilde
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: von Versen-Höynck
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitäsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Carsten Schriver
authors.initials: CS
authors.lastname: Højskov
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitäsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Charité-Universitätsmedizin Berlin, Campus Berlin Buch, Berlin, Germany; Department of Cardiology and Nephrology, HELIOS Klinikum Berlin, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: HansChristian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Henrik Thybo
authors.initials: HT
authors.lastname: Christesen
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitäsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. Electronic address: nadine.haase@mdc-berlin.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Haase
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001795:Blood Pressure Determination; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000209:etiology; D011247:Pregnancy; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D065667:Renal Elimination; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000150:complications*
chemical_list: C534931:AGT protein, human; D000808:Angiotensinogen; D014807:Vitamin D; D012083:Renin
keywords: Renin-angiotensin system; transgenic rodents