Cleal J K, Hargreaves M R, Poore K R, Tang J C Y, Fraser W D, Hanson M A, Green L R
1Institute of Developmental Sciences, Faculty of Medicine,University of Southampton,Southampton,Hampshire,UK.
2Department of Medicine,Norwich Medical School,University of East Anglia,Norwich,Norfolk,UK.
J Dev Orig Health Dis. 2017 Jun;8(3):370-381. doi: 10.1017/S2040174417000149. Epub 2017 Mar 22.
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.
维生素D和其他营养物质（如氨基酸、脂肪和葡萄糖）通过胎盘向胎儿的转运对母体和胎儿的营养信号敏感。我们研究了母体热量限制对胎儿维生素D状态、营养物质转运基因[芳香族T型氨基酸转运体-1（TAT-1）；甘油三酯水解酶/脂蛋白摄取促进因子脂蛋白脂肪酶（LPL）]和维生素D稳态[CYP27B1；维生素D受体（VDR）]在胎盘的表达的影响，以及它们与胎儿心血管功能和骨骼肌生长标志物的关联。怀孕的绵羊接受100%的总可代谢能量（ME）需求（对照组）、植入前期（PI40，妊娠第1 - 31天）40%的总ME需求或妊娠晚期（L，妊娠第104 - 127天）50%的总ME需求。在妊娠0.86时，与对照组相比，PI40和L组母体营养不足组胎儿（而非母体）血浆25-羟基维生素D（25OHD）浓度较低（P<0.01）。与对照组相比，PI40组胎盘CYP27B1信使核糖核酸（mRNA）水平升高（P<0.05）。在所有组中，胎儿血浆25OHD浓度较高与骨骼肌肌纤维和毛细血管密度较高相关（P<0.05）。在胎盘中，较高的VDR mRNA水平与较高的TAT-1（P<0.05）和LPL（P<0.01）mRNA水平相关。仅在PI40母体营养不足组中，胎儿血浆25OHD浓度降低可能部分是由胎盘CYP27B1改变介导的。胎盘VDR mRNA水平与营养物质转运基因之间的关联表明，胎盘可能在面对母体饮食挑战时整合营养信号并改变胎儿生理的一种方式。
