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Prepregnancy Vitamin D Deficiency and Placental Growth and Development in Mice
Author(s) -
Gernand Alison D,
Cantorna Margherita T,
Diaz Francisco J,
Snyder Lyndsay M,
Hester James M,
Vasudevan Sreelakshmi,
Kamat Manasi M,
Ott Troy L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.915.12
Subject(s) - fetus , medicine , endocrinology , placenta , pregnancy , vitamin d deficiency , placental growth factor , biology , vitamin , preeclampsia , gestation , intrauterine growth restriction , vitamin d and neurology , calcitriol receptor , genetics
The global prevalence of vitamin D deficiency in women of reproductive age is high. Vitamin D deficiency is linked to numerous adverse pregnancy outcomes with placental origins, including preeclampsia and fetal growth restriction. Our objective was to examine the effect of prepregnancy and early pregnancy vitamin D deficiency on placental growth and vascular development. We modeled vitamin D deficiency using a Cyp27B1 genetic knockout (KO) mouse fed no dietary vitamin D (n=6); these mice cannot convert the circulating vitamin D metabolite to the biologically active metabolite. Wild‐type (WT) mice with a vitamin D sufficient diet were the control (n=6). All mice were fed the respective diet from 3 weeks of age onward. At 8 weeks of age, mice were mated to genetically dissimilar males to produce allogeneic embryos. Mice were euthanized at 12.5 days gestation and placental and fetal morphometry was measured which included fetal and placental weights and the area of the middle cross‐section of the placenta. Placental mRNA was estimated by qPCR for angiogenic proteins (angiopoeitin‐1 (Ang‐1), Ang‐2, vascular endothelial growth factor a (VEGFa), VEGF receptor 1 (VEGFR1), and placental growth factor (PlGF)). Linear regression models were fit with a generalized estimating equation (GEE) for each outcome examined to account for the clustering of placentas/fetuses within mothers. An interaction by fetal sex was also examined for each outcome. KO mice and WT mice had a similar number viable fetuses and a similar percentage of male fetuses at 12.5 days (7.0 vs. 8.3 per mother and 50% vs. 36%, respectively; both p>0.05). There were no statistically significant differences for KO vs. WT offspring for fetal weight or crown‐rump length (p>0.05). There were also no observed differences for placental weight between groups (p>0.05). However, the total area of the cross‐section of the placenta and the fetal area of the placenta were each larger for KO vs. WT mice (1.04 mm, p=0.024, and 0.600 mm, p=0.046, respectively). There were no statistically significant differences for KO vs. WT in placental Ang‐1, Ang‐2, or VEGFR‐1 mRNA (all p>0.05) but, KO placentas exhibited higher expression of PlGF (p=0.015). Further, placentas from KO mothers exhibited lower expression of VEGFa compared to WT placentas and this effect was stronger in placentas of female offspring (p=0.055 for interaction). Prepregnancy and early pregnancy maternal vitamin D deficiency in mice caused differential expression of angiogenic factors and growth of the placenta. These factors should further be studied in human pregnancies. Support or Funding Information Penn State College of Health and Human Development