Considerable amounts of long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid and docosahexaenoic acid (DHA, 22:6n-3), are deposited in fetal tissues during pregnancy; and this process is facilitated by placental delivery. Nevertheless, the mechanisms involved in LC-PUFA placental transfer remain unclear. Stable isotope techniques have been used to study human placental fatty acid transfer in vivo. These studies have shown a significantly higher ratio of (13)C-DHA in cord to maternal plasma compared with other fatty acids, which reflects a higher placental DHA transfer. In addition, a selective DHA accumulation in placental tissue, relative to other fatty acids, has been reported. The materno-fetal transfer of fatty acids is a slow process that requires ≥12 h. A high incorporation of dietary (13)C-DHA into maternal plasma phospholipids appears to be important for placental uptake and transfer. DHA in cord blood lipids correlates with placental messenger RNA expression of fatty acid transport protein (FATP)-4, compatible with a role of FATP-4 in DHA transfer. Impaired materno-fetal LC-PUFA transport has been proposed in pregnancies complicated by abnormal placental function (eg, due to gestational diabetes mellitus or intrauterine growth restriction), which should be addressed in future studies. Given that placental DHA transfer is important for child outcomes, elucidation of its potential modulation by transport mechanisms, maternal diet, and disease appears to be important.

Twelve hours after oral application of (13)C-labeled FAs, relatively stable tracer enrichment was achieved. We found a significantly higher ratio of (13)C-DHA concentrations in cord plasma than in maternal plasma, which was higher than that for the other studied FAs. (13)C-DHA is predominantly esterified into phospholipids and triglycerides in maternal plasma, which may facilitate its placental uptake and transfer.

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Better knowledge on the disturbed mechanisms implicated in materno-fetal long-chain polyunsaturated fatty acid (LC-PUFA) transfer in pregnancies with gestational diabetes mellitus (GDM) may have potentially high implications for later on in effective LC-PUFA supplementation. We studied in vivo placental transfer of fatty acids (FA) using stable isotope tracers administrated to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally [(13)C]palmitic, [(13)C]oleic and [(13)C]linoleic acids, and [(13)C]docosahexaenoic acid ((13)C-DHA) 12 h before elective caesarean section. Maternal blood samples were collected at -12, -3, -2, and -1 h, delivery, and +1 h. Placental tissue and venous cord blood were also collected. FA were quantified by gas chromatography (GC) and (13)C enrichments by GC-isotope ratio mass spectrometry. [(13)C]FA concentration was higher in total lipids of maternal plasma in GDM vs. controls, except for [(13)C]DHA. Moreover, [(13)C]DHA showed lower placenta/maternal plasma ratio in GDM vs. controls and significantly lower cord/maternal plasma ratio. For the other studied FA, ratios were not different between GDM and controls. Disturbed [(13)C]DHA placental uptake occurs in both GDM treated with diet or insulin, whereas the last ones also have lower [(13)C]DHA in venous cord. The tracer study pointed toward impaired placental DHA uptake as critical step, whereas the transfer of the rest of [(13)C]FA was less affected. GDM under insulin treatment could also have higher fetal fat storage, contributing to reduce [(13)C]DHA in venous cord. DHA transfer to the fetus was reduced in GDM pregnancies compared with controls, which might affect the programming of neurodevelopment in their neonates.

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The concentration of long chain polyunsaturated fatty acid (LCPUFA) in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA) during gestation and development of cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is the maternal circulation. Both in vitro and human in vivo studies using labeled fatty acids have shown preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA) and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts, and even re-esterified and stored in lipid droplets. Although trophoblast cells are not specialized for lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ) and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA-synthetases and adipophilin or other enzymes involved in lipolysis, modifying the rate of placental transfer, and metabolism. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge of the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.

The treatment of the microscopic disease following complete cytoreduction with HIPEC in patients with advanced ovarian cancer is effective and can prolong disease-free survival. This survival benefit was not seen in undifferentiated tumors.

The functionality of the placenta may affect neonatal adiposity and fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Fetal macrosomia and its complications may occur even in adequately controlled gestational diabetic (GDM) mothers, suggesting that maternal glycemia is not the only determinant of fetal glycemic status and wellbeing. We studied in vivo the placental transfer of fatty acids (FA) labeled with stable isotopes administered to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally ¹³C-palmitic, ¹³C-oleic, and ¹³C-linoleic acids and ¹³C-docosahexaenoic acid (¹³C-DHA) 12 h before an elective caesarean section. FA were quantified by gas chromatography and ¹³C enrichments by gas chromatography-isotope ratio mass spectrometry. The ¹³C-FA concentration was higher in total lipids of maternal plasma in GDM patients versus controls, except for ¹³C-DHA. Moreover, ¹³C-DHA showed a lower placenta/maternal plasma ratio in GDM patients versus controls and a significantly lower cord/maternal plasma ratio. Other FA ratios studied were not different between GDM and controls. A disturbed ¹³C-DHA placental uptake occurred in GDM patients treated with diet or insulin, while the latter also had lower ¹³C-DHA levels in the venous cord. The tracer study pointed towards an impaired placental DHA uptake as a critical step, while the transfer of other ¹³C-FA was less affected. Patients with GDM treated with insulin could also have a greater fetal fat storage, which may have contributed to the reduced ¹³C-DHA in the venous cord observed. The DHA transfer to the fetus was reduced in GDM pregnancies compared to controls. This might have an influence on fetal neurodevelopment and long-term consequences for the child.