Adaptive responses to maternal nutrient restriction alter placental transport in ewes

Adaptive responses to maternal nutrient restriction alter placental transport in ewes
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DOI:
10.1016/j.placenta.2020.05.002
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发表时间:
2020-07-01
期刊:
影响因子:
3.8
通讯作者:
Satterfield, M. Carey
Satterfield, M. Carey
中科院分区:
医学3区
文献类型:
--
作者:
Edwards, Ashley K.;McKnight, Sorin M.;Satterfield, M. Carey

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前言:母体营养物质的分配、子宫胎盘血流、转运蛋白活性和胎儿胎盘代谢调节着营养物质向胎儿的输送。营养物质供应不足或供应不足会导致胎儿宫内生长受限,这是新生儿发病率和死亡率的主要原因。母体营养限制可以导致IUGR,但只会导致不可预见的个体亚群。方法:通过胚胎移植产生单胎绵羊妊娠,以阐明调节胎儿营养供应的潜在机制。怀孕的母羊从妊娠35天到尸检的125天期间接受50%NRC(NR;n=24)或100%NRC(n=7)的饮食。母体体重与胎儿体重无相关性;因此,比较了6个最重(NR非IUGR)和5个最轻(NR IUGR)的营养限制母羊胎儿和7个100%的NRC胎儿的营养利用率差异。结果:与NR非IUGR和100%NRC相比,NR IUGR胎儿循环中的胰岛素、多种氨基酸及其代谢产物减少。相比之下,胎儿液中的葡萄糖在不同组之间没有差异。与非IUGR和100%NRC相比,NIUGR组的胎盘体积和胎儿/母体界面长度减少了近两倍。氨基酸浓度的变化与胎盘中阳离子(SLC7A2、SLC7A6和SLC7A7)和大中性(SLC38A2)氨基酸转运蛋白的表达变化有关。讨论:结果建立了一种新的方法来研究绵羊胎盘对母体营养不良的适应,并支持氨基酸和多胺是绵羊胎盘和胎儿生长的关键介质的假说。
Introduction: Maternal nutrient partitioning, uteroplacental blood flow, transporter activity, and fetoplacental metabolism mediate nutrient delivery to the fetus. Inadequate availability or delivery of nutrients results in intrauterine growth restriction (IUGR), a leading cause of neonatal morbidity and mortality. Maternal nutrient restriction can result in IUGR, but only in an unforeseeable subset of individuals.Methods: To elucidate potential mechanisms regulating fetal nutrient availability, singleton sheep pregnancies were generated by embryo transfer. Pregnant ewes received either a 50% NRC (NR; n = 24) or 100% NRC (n = 7) diet from gestational Day 35 until necropsy on Day 125. Maternal weight did not correlate with fetal weight; therefore, the six heaviest (NR Non-IUGR) and five lightest (NR IUGR) fetuses from nutrient-restricted ewes, and seven 100% NRC fetuses, were compared to investigate differences in nutrient availability.Results: Insulin, multiple amino acids, and their metabolites, were reduced in fetal circulation of NR IUGR compared to NR Non-IUGR and 100% NRC pregnancies. In contrast, glucose in fetal fluids was not different between groups. There was a nearly two-fold reduction in placentome volume and fetal/maternal interface length in NR IUGR compared to NR Non-IUGR and 100% NRC pregnancies. Changes in amino acid concentrations were associated with altered expression of cationic (SLC7A2, SLC7A6, and SLC7A7) and large neutral (SLC38A2) amino acid transporters in placentomes.Discussion: Results establish a novel approach to study placental adaptation to maternal undernutrition in sheep and support the hypothesis that amino acids and polyamines are critical mediators of placental and fetal growth in sheep.