Placental Compartmentalization of Lipid Metabolism: Implications for Singleton and Twin Pregnancies

Abstract

Introduction. The study of placental lipid metabolism in uncomplicated pregnancies has not been 2 developed in the literature to date. Its importance lies in expanding the knowledge of placental function to 3 enable comparison with pathological pregnancies in future research. The aim of the present study was to 4 compare the lipid metabolic activity and storage of the maternal and fetal sides of the placenta in healthy 5 pregnancies. Moreover, we compare singleton vs. twin pregnancies to determine if placental metabolic 6 needs differ. 7Material and Methods. We analyzed placental explants from uncomplicated pregnancies, 20 from 8 singleton and 8 from bichorial-biamniotic twin pregnancies (n=28). Six cotyledon fragments were 9 collected from each placenta at different distances from the umbilical cord, three close to the chorionic 10 plate (hereinafter we will refer to them as "fetal side") and another three close to the anchoring villi into 11 the decidua basalis (referred to as "maternal side"). The samples were analyzed for quantitative assay 12 placental fatty acid oxidation (FAO) and esterification (FAE) activities and triglyceride levels. The 13 location of lipid storage in the chorionic villi was assessed by Oil red-O staining. 14Results. Placental fatty acid oxidation did not show differences when comparing the maternal and fetal 15 sides of the placenta or between single and twin pregnancies. When comparing placental sides, FAE was 16 increased two-fold in the maternal side compared to the fetal side of the placenta (P = 0.013). The 17 tendency for lipogenesis in the placenta was exemplified by the FAE/FAO ratio, which was a 37.1% 18 higher on the maternal side (P = 0.019). Despite this, triglyceride levels were five times higher in the fetal 19 side than in the maternal one (P = 0.024). When analyzing singleton vs. twins, FAE was superior in the 20 fetal side in multiple pregnancies (×2.6, P = 0.007) and the FAE/FAO ratio was significantly higher in 21 twins than in singleton pregnancies, on both sides of the placenta. Despite this finding, triglyceride levels 22 were similar in twin and singleton pregnancies. Comparing the placentas of twins in the same pregnancy, 23 there were no differences in lipid metabolism (FAO or FAE) or placental triglyceride levels between the 24 two co-twins. Using Oil red-O staining, lipid storage in chorionic villi was found to be located on the 25 syncytiotrophoblast cells and not in the connecting axis. 26Conclusion. The maternal side of the placenta is more active in the esterification of fatty acids, while the 27 storage of neutral lipids concentrates on the fetal side. Moreover, multiple gestations have increased 28 esterification without changes in the concentration of placental triglycerides, probably due to a higher 29 transfer to the fetal circulation in response to the greater energy demand from twin fetuses. 30

Decreased Fatty Acid Oxidation Gene Expression in Pre-Eclampsia According to the Onset and Presence of Intrauterine Growth Restriction

“…A decrease in the gene expression of FAO enzymes in pre-eclampsia, especially on the fetal side of the placenta, leads to the lower utilization of FFA by the placenta with the accumulation of triglycerides on the fetal side, as previously reported [ 16 ]. Theoretically, the pathogenic sequence can start with decreased placental FAO, which would increase the FFA and triglyceride placental and maternal serum levels, leading to immune-resistance, lipotoxicity, and finally, endothelial damage.…”

“…Therefore, placental FAO disorders might play a role in the pathophysiology of pre-eclampsia. In addition, we have previously demonstrated that in healthy pregnant women, the maternal side of the placenta is more active in the esterification of fatty acids, whereas lipid storage concentrates more on the fetal side [ 16 ].…”

The Relationship between Angiogenic Factors and Energy Metabolism in Preeclampsia

“…In healthy early pregnancy, insulin stimulates lipogenesis. However, in mid and late pregnancy, insulin leads to an intensification of lipolysis of fatty deposits, leading to maternal hyperlipidemia, specifically due to hypertriglyceridemia and FFA, to provide energy for the growing fetus [ 28 , 52 , 53 , 54 ]. In preeclampsia, there is an increase in FFA [ 11 , 52 ], hypertriglyceridemia [ 55 , 56 ], and higher oxidized-LDL in maternal serum [ 57 , 58 ].…”

“…Measurement of fatty acid oxidation (FAO) in placental explants was performed according to the method previously described by our group [ 25 , 26 , 27 , 28 ]. It was quantified as nanomoles of [3H]-palmitate per gram of tissue per hour (nmol/g/h).…”

Association of placental toll-like receptor 4 and fatty acid transport protein expression with neonatal weight

“…Our result showed that the levels of TG in elbow vein and umbilical cord blood for 4 groups were statistically different, and the TG level of macrosomia group was significantly increased. TG cannot be directly used by the fetus through the placental barrier, so it needs to be hydrolyzed into small molecular substances by lipase and then transported through the placenta into the umbilical vein blood, which is absorbed by the fetus, resulting in the increase of neonatal weight [18].…”