IGF2 May Enhance Placental Fatty Acid Metabolism by Regulating Expression of Fatty Acid Carriers in the Growth of Fetus and Placenta during Late Pregnancy in Pigs

Abstract

Fatty acids (FAs) are essential substances for the growth and development of the fetus and placenta. The growing fetus and placenta must obtain adequate FAs received from the maternal circulation and facilitated by various placental FA carriers, including FA transport proteins (FATPs), FA translocase (FAT/CD36), and cytoplasmic FA binding proteins (FABPs). Placental nutrition transport was regulated by imprinted genes H19 and insulin-like growth factor 2 (IGF2). Nevertheless, the relationship between the expression patterns of H19/IGF2 and placental fatty acid metabolism throughout pig pregnancy remains poorly studied and unclear. We investigated the placental fatty acid profile, expression patterns of FA carriers, and H19/IGF2 in the placentae on Days 40 (D40), 65 (D65), and 95 (D95) of pregnancy. The results showed that the width of the placental folds and the number of trophoblast cells of D65 placentae were significantly increased than those of D40 placentae. Several important long-chain FAs (LCFAs), including oleic acid, linoleic acid, arachidonatic acid, eicosapentaenoic acid, and docosatetraenoic acid, in the pig placenta showed dramatically increased levels throughout pregnancy. The pig placenta possessed higher expression levels of CD36, FATP4, and FABP5 compared with other FA carriers, and their expression levels had significantly upregulated 2.8-, 5.6-, and 12.0-fold from D40 to D95, respectively. The transcription level of IGF2 was dramatically upregulated and there were corresponding lower DNA methylation levels in the IGF2 DMR2 in D95 placentae relative to D65 placentae. Moreover, in vitro experimentation revealed that the overexpression of IGF2 resulted in a significant increase in fatty acid uptake and expression levels of CD36, FATP4, and FABP5 in PTr2 cells. In conclusion, our results indicate that CD36, FATP4, and FABP5 may be important regulators that enhance the transport of LCFAs in the pig placenta and that IGF2 may be involved in FA metabolism by affecting the FA carriers expression to support the growth of the fetus and placenta during late pregnancy in pigs.

Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

“…The selective uptake may involve intracellular metabolic channeling and a selective supply to the fetal circulation [ 2 , 47 , 48 ]. Several protein families were implicated in directional FA transport in the placenta: the membranal FATPs, FA translocase (FAT/CD36), and the cytoplasmic FABPs [ 2 , 48 , 49 ]. The uptake and accumulation of FAs are regulated by FABPs; FABP3, FABP4, FABP5, and FABP7 are expressed in cells with high FA requirements, such as the placenta [ 48 , 50 , 51 ].…”