National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India.
Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
J Nutr Biochem. 2021 Oct;96:108784. doi: 10.1016/j.jnutbio.2021.108784. Epub 2021 May 29.
The maternal n-3 polyunsaturated fatty acid (PUFA) deficiency on decidual vascular structure and angiogenesis in mice placenta was investigated. Namely, we studied uterine artery remodeling, fatty acid metabolism, and placental epigenetic methylation in this animal model. Weanling female Swiss albino mice were fed either alpha-linolenic acid (18:3 n-3, ALA) deficient diets (0.13% energy from ALA) or a sufficient diet (2.26% energy from ALA) throughout the study. The dietary n-3 PUFA deficiency altered uteroplacental morphology and vasculature by reversing luminal to vessel area and increased luminal wall thickness at 8.5-12.5gD. Further, placentas (F0 and F1) showed a significant decrease in the expression of VCAM1, HLAG proteins and an increase in MMP9, KDR expression. The conversion of ALA to long-chain (LC) n-3 PUFAs was significantly decreased in plasma and placenta during the n-3 deficiency state. Reduced n-3 LCPUFAs increased the placental expression of intracellular proteins FABP3, FABP4, and ADRP to compensate decreased availability of these fatty acids in the n-3 deficient mice. The N-3 PUFA deficiency significantly increased the 5-methylcytosine levels in the placenta but not in the liver. The alteration in DNA methylation continued to the next generation in the placental epigenome with augmented expression of DNMT3A and DNMT3B. Our study showed that maternal n-3 PUFA deficiency alters placental vascular architecture and induces epigenetic changes suggesting the importance of n-3 PUFA intake during the development of the fetus. Moreover, the study shows that the placenta is the susceptible target for epigenetic alteration in maternal deficiency n-3 fatty acids.
本研究旨在探讨母体二十二碳六烯酸（n-3 PUFA）缺乏对小鼠胎盘滋养层血管结构和血管生成的影响。具体而言，我们在该动物模型中研究了子宫动脉重塑、脂肪酸代谢和胎盘表观遗传甲基化。研究期间，将断乳雌性瑞士白化病小鼠分别用缺乏α-亚麻酸（18：3 n-3，ALA；能量的 0.13%来自 ALA）的饮食或充足的饮食（能量的 2.26%来自 ALA）喂养。饮食中 n-3 PUFA 缺乏通过逆转腔室到血管区域的比例和增加 8.5-12.5gD 时的腔室壁厚度来改变子宫胎盘形态和血管。此外，胎盘（F0 和 F1）表现出 VCAM1、HLAG 蛋白表达显著降低，MMP9、KDR 表达增加。在 n-3 缺乏状态下，血浆和胎盘内 ALA 向长链（LC）n-3 PUFA 的转化显著减少。减少的 n-3 LCPUFA 增加了胎盘内 FABP3、FABP4 和 ADRP 等细胞内蛋白的表达，以补偿 n-3 缺乏小鼠中这些脂肪酸的可用性降低。n-3 PUFA 缺乏显著增加了胎盘的 5-甲基胞嘧啶水平，但在肝脏中没有增加。在胎盘表观基因组中，这种 DNA 甲基化的改变持续到下一代，DNMT3A 和 DNMT3B 的表达增加。我们的研究表明，母体 n-3 PUFA 缺乏改变胎盘血管结构并诱导表观遗传改变，提示胎儿发育过程中 n-3 PUFA 摄入的重要性。此外，该研究表明，胎盘是母体缺乏 n-3 脂肪酸时易发生表观遗传改变的靶器官。
