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.

研究了母体 n-3 多不饱和脂肪酸 (PUFA) 缺乏对小鼠胎盘蜕膜血管结构和血管生成的影响。也就是说，我们研究了该动物模型中的子宫动脉重塑、脂肪酸代谢和胎盘表观遗传甲基化。在整个研究过程中，断奶雌性瑞士白化小鼠被喂食缺乏 α-亚麻酸（18:3 n-3，ALA）的饮食（0.13% 的能量来自 ALA）或充足的饮食（2.26% 的能量来自 ALA）。饮食中的 n-3 PUFA 缺乏改变了子宫胎盘形态和脉管系统，通过将管腔区域逆转为血管区域，并在 8.5-12.5gD 时增加管腔壁厚度。此外，胎盘（F0 和 F1）显示 VCAM1、HLAG 蛋白表达显着降低，MMP9、KDR 表达增加。在 n-3 缺乏状态下，血浆和胎盘中 ALA 向长链 (LC) n-3 PUFA 的转化显着降低。减少的 n-3 LCPUFAs 增加了细胞内蛋白质 FABP3、FABP4 和 ADRP 的胎盘表达，以补偿这些脂肪酸在 n-3 缺陷小鼠中的可用性降低。N-3 PUFA 缺乏显着增加了胎盘中的 5-甲基胞嘧啶水平，但在肝脏中没有。DNA甲基化的改变在胎盘表观基因组中持续到下一代，DNMT3A和DNMT3B的表达增加。我们的研究表明，母体 n-3 PUFA 缺乏会改变胎盘血管结构并诱导表观遗传变化，这表明 n-3 PUFA 摄入在胎儿发育过程中的重要性。而且，