Reduced fetal vitamin D status by maternal undernutrition during discrete gestational windows in sheep.

J K Cleal,L R Green,W D Fraser,K R Poore,M A Hanson,J C Y Tang,M R Hargreaves

doi:10.1017/s2040174417000149

Abstract

Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport [aromatic T-type amino acid transporter-1 (TAT-1); triglyceride hydrolase/lipoprotein uptake facilitator lipoprotein lipase (LPL)] and vitamin D homeostasis [CYP27B1; vitamin D receptor (VDR)], and their association with markers of fetal cardiovascular function and skeletal muscle growth. Pregnant sheep received 100% total metabolizable energy (ME) requirements (control), 40% total ME requirements peri-implantation [PI40, 1-31 days of gestation (dGA)] or 50% total ME requirements in late gestation (L, 104-127 dGA). Fetal, but not maternal, plasma 25-hydroxy-vitamin D (25OHD) concentration was lower in PI40 and L maternal undernutrition groups (P<0.01) compared with the control group at 0.86 gestation. PI40 group placental CYP27B1 messenger RNA (mRNA) levels were increased (P<0.05) compared with the control group. Across all groups, higher fetal plasma 25OHD concentration was associated with higher skeletal muscle myofibre and capillary density (P<0.05). In the placenta, higher VDR mRNA levels were associated with higher TAT-1 (P<0.05) and LPL (P<0.01) mRNA levels. In the PI40 maternal undernutrition group only, reduced fetal plasma 25OHD concentration may be mediated in part by altered placental CYP27B1. The association between placental mRNA levels of VDR and nutrient transport genes suggests a way in which the placenta may integrate nutritional cues in the face of maternal dietary challenges and alter fetal physiology.

Highlights

Poor nutrition in pregnancy and fetal adaptive responses are linked to increase the risk of chronic diseases in later life, including diabetes and cardiovascular disease.[1]
We have shown that both early gestation and late gestation maternal undernutrition result in lower fetal 25OHD plasma concentrations in late gestation
Our observation of an association between fetal vitamin D status and fetal skeletal muscle structure, and between the placental messenger RNA (mRNA) for vitamin D receptor (VDR) and nutrient transporter genes, suggests additional mechanisms through which fetal physiology may be influenced in this undernutrition model

Summary

Introduction

Poor nutrition in pregnancy and fetal adaptive responses are linked to increase the risk of chronic diseases in later life, including diabetes and cardiovascular disease.[1] The placenta is the only route for nutrients, including 25-hydroxy-vitamin D (25OHD), to reach the fetus from the mother; it is an important factor in determining the nutrient ‘signal’ received by the fetus. The micronutrient vitamin D comes from diet (ergocalciferol, D2; cholecalciferol, D3) or the action of sunlight on skin (cholecalciferol, D3). Both forms are hydroxylated in the liver to 25OHD2 or 25OHD3 (together in this paper they are referred to as 25OHDtotal). Derived 25OHD is converted to 1,25-dihydroxy-vitamin D (1,25(OH)2D)[2] or D (1,25(OH) 2D)[3] by 1-α-hydroxylase (CYP27B1) in the fetal kidney and placenta.[13,14,15] The enzyme 24-α-hydroxylase (CYP24A1)

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