Prepregnancy Vitamin D Deficiency and Placental Development in Mice

Abstract

Maternal vitamin D deficiency is a public health problem worldwide and is linked to numerous adverse pregnancy outcomes with placental origins. Our objective was to examine the effect of prepregnancy vitamin D deficiency on placental vascular development. We modeled vitamin D deficiency using a Cyp27B1 genetic knockout (KO) mouse with no dietary vitamin D (n=6); 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. Placental mRNA was estimated by qPCR for angiogenic proteins (angiopoeitin-1 (Ang-1), Ang-2, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF)). KO mice had fewer viable fetuses at 12.5 days compared to WT (6.2 vs. 8.5, p=0.033). There were no statistically significant differences for KO vs. WT in placental or fetal weights or placental Ang-1, Ang-2, or PIGF mRNA (all p>0.05). However, KO placentas exhibited a 27% reduction in VEGF expression compared to WT placentas (p=0.047, Figure 1). Fewer KO mice established pregnancy after mating, yet the study design did provide sufficient sample size to adequately test this effect. Prepregnancy maternal vitamin D deficiency in mice caused lower litter size among mice that became pregnant and decreased placental VEGF mRNA abundance. Ongoing work is examining the mechanisms for vitamin D effects on placental development. Support: Penn State College of Health and Human Development