Clements M R, Fraser D R
Dunn Nutritional Laboratory, University of Cambridge, United Kingdom.
J Clin Invest. 1988 Jun;81(6):1768-73. doi: 10.1172/JCI113518.
The prevention of neonatal rickets by oral supplementation with vitamin D2 (ergocalciferol) has tended to obscure our ignorance of the natural mechanism by which young mammals receive an adequate supply of vitamin D. To investigate the possibility of specific intrauterine transfer and storage of vitamin D in fetal tissues, vitamin D-deficient female rats were given depot injections of 3H- or 14C-labeled vitamin D3 (cholecalciferol) before mating and the 3H-labeled animals were killed at stages during the last third of gestation. Analysis of lipid extracts from whole fetuses revealed a linear increase in the concentration of 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and D3 itself between days 14 and 19 of gestation. During this period the elimination half-time of 3H-labeled molecules in maternal plasma fell from 27.1 to 4.4 d, suggesting that a specific mechanism was transferring vitamin D molecules into the fetuses. The vitamin was stored predominantly as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3, with the highest concentrations in fetal muscle. Immediately after birth, pups from 3H- and 14C-labeled mothers were exchanged and later killed after 1-3 wk of suckling. Analysis of total lipid extracts for 3H and 14C content determined the relative contributions of vitamin D supplied before birth via the placenta and after birth in the maternal milk. The vitamin D content of the rat milk was relatively high, between 1.0 and 3.5 micrograms/liter. Nevertheless, the supply of vitamin D in utero, rather than from milk, was the main determinant of vitamin D status in early neonatal life. This is the first indication in a mammal of a specific transfer mechanism that allows the fetus to accumulate vitamin D from the mother during the last third of gestation.
通过口服补充维生素D2(麦角钙化醇)预防新生儿佝偻病,往往掩盖了我们对幼年哺乳动物获得充足维生素D天然机制的无知。为了研究维生素D在胎儿组织中特异性宫内转运和储存的可能性,在交配前给维生素D缺乏的雌性大鼠注射3H或14C标记的维生素D3(胆钙化醇),并在妊娠最后三分之一阶段的不同时期处死3H标记的动物。对整个胎儿的脂质提取物分析显示,在妊娠第14天至19天期间,25-羟基维生素D3、24,25-二羟基维生素D3和维生素D3本身的浓度呈线性增加。在此期间,母体血浆中3H标记分子的消除半衰期从27.1天降至4.4天,这表明存在一种将维生素D分子转运到胎儿体内的特异性机制。维生素主要以25-羟基维生素D3和24,25-二羟基维生素D3的形式储存,在胎儿肌肉中的浓度最高。出生后立即交换来自3H和14C标记母亲的幼崽,在哺乳1-3周后处死。分析总脂质提取物中的3H和14C含量,确定出生前通过胎盘供应的维生素D和出生后母乳中维生素D的相对贡献。大鼠乳汁中的维生素D含量相对较高,在1.0至3.5微克/升之间。然而,子宫内而非乳汁中维生素D的供应是新生儿早期维生素D状态的主要决定因素。这是首次在哺乳动物中发现一种特异性转运机制,使胎儿在妊娠最后三分之一阶段能够从母体积累维生素D。