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.
Keywords: Alpha-linolenic acid (ALA); DNA methylation; Placenta; Uterine arterial remodeling; n-3 PUFA deficiency.
Copyright © 2021 Elsevier Inc. All rights reserved.