Eicosapentaenoic and docosahexaenoic acid supplementation during early gestation modified relative abundance on placenta and fetal liver tissue mRNA and concentration pattern of fatty acids in fetal liver and fetal central nervous system of sheep

Abstract

In sheep, polyunsaturated fatty acid (PUFA) supplementations in late gestation increases the growth of offspring; however, there is a lack of evidence on the effect of PUFA supplementation during early gestation. Thus, the objective of this study was to evaluate the effect of dietary supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in early gestation pregnant ewes on fatty acid concentration of fetal liver (FL) and fetal central nervous system (FCNS), and relative abundance of the mRNA for genes associated with transport and metabolism of fatty acids in FL and placenta. A total of 12 ewes, block for stage of gestation were fed a diet containing 1.6% (dry matter basis) monounsaturated fatty acids (MUFA) or EPA+DHA during the first 45 days of gestation. A cesarean section was conducted on day 45 of gestation to collect placenta (caruncle and cotyledon), FL, and FCNS. Relative abundance of mRNA in FL and FCNS and fatty acid concentration were analyzed using a 2x2 factorial arrangement of treatments considering fatty acid supplementation and tissue as the main factors. Concentrations of C18:1 isomers increase (P < 0.05) in FL and FCNS with MUFA supplementation; the FL and FCNS had a greater concentration of C20:3(n-6), C20:3(n-3), C22:1, C22:5 and C22:6 (P < 0.05) with EPA+DHA supplementation. In FL, the relative abundance of LPL mRNA was greater (P = 0.02) as a result of MUFA supplementation. In placenta, there was a FA x tissue interaction for relative abundance of DNMT3b and FFAR-4 mRNA (P < 0.05). Fetus from MUFA-supplemented dams had a greater relative abundance of FABP-4 mRNA (P < 0.05). Results indicate supplementation with EPA+DHA during early gestation increases the total EPA and DHA in FL. For the placenta, EPA+DHA supplementation led to an increase in the relative abundance of lipid mRNA for transport genes.

Effects of maternal dietary omega-3 polyunsaturated fatty acids and methionine during late gestation on fetal growth, DNA methylation, and mRNA relative expression of genes associated with the inflammatory response, lipid metabolism and DNA methylation in placenta and offspring’s liver in sheep

“…Supplementation with omega-3 PUFA or Met has beneficial effects on development and growth of the offspring, and supplementation with one or the other has showed to modify the expression of immune mediators, enzymes involved in DNA methylation, and increased growth, but the effects of supplementation with both nutrients on fetus growth, gene expression of cytokines in the NF-κB pathway, enzymes present in the methionine cycle, DNA methylation, and in the RvD1 omega-3 PUFA metabolic pathway, as well as on global DNA methylation of fetal tissues, have not been studied. According to previous studies [ 4 , 11 , 28 ], we expect that fetus growth from dams supplemented with these two nutrients will be associated with an increase in the mRNA expression of the enzymes that participates in DNA methylation (DNMT), Met cycle, and RvD1 metabolic pathway after PUFA supplementation. We assume that PUFA supplementation would modified the expression of DNMT enzymes and Met supplementation will increase methyl donors, thus increasing DNA methylation.…”

“…Omega-3 PUFA are ligands for transcription factors involved in gene regulation of metabolic and developmental processes [ 9 ]. Supplementation with omega-3 PUFA have shown changes not only in offspring growth [ 3 ], but also changes in the mRNA expression on the fetal part of the placenta [ 11 ]. One of the genes affected by the omega-3 PUFA supplementation was the DNA-methyltransferase (DNMT)-3A [ 11 ], an enzyme that methylate DNA.…”

“…Supplementation with omega-3 PUFA have shown changes not only in offspring growth [ 3 ], but also changes in the mRNA expression on the fetal part of the placenta [ 11 ]. One of the genes affected by the omega-3 PUFA supplementation was the DNA-methyltransferase (DNMT)-3A [ 11 ], an enzyme that methylate DNA. Another gene in the cotyledon affected by maternal supply of omega-3 PUFA was free fatty acid receptor (FFAR)-4 [ 11 ], a gene involved in lipid metabolism.…”

“…One of the genes affected by the omega-3 PUFA supplementation was the DNA-methyltransferase (DNMT)-3A [ 11 ], an enzyme that methylate DNA. Another gene in the cotyledon affected by maternal supply of omega-3 PUFA was free fatty acid receptor (FFAR)-4 [ 11 ], a gene involved in lipid metabolism. Similarly, supplementation with omega-3 PUFA has affected the mRNA expression of genes involved in lipid metabolism within the liver, but much of this research has been done in adult animals [ 12 , 13 ].…”

“…Omega-3 PUFA can modulate the expression of genes associated with the inflammatory response, lipid metabolism, and DNA methylation [ 8 , 9 , 11 ]. On the other hand, supplementation with Met can increase the availability of methyl donors affecting DNA methylation [ 25 ], and the expression of genes associated with the inflammatory response [ 21 – 23 ].…”