Metabolism of 13C-labeled fatty acids in term human placental explants by liquid chromatography mass spectrometry

: Placental lipid transport and metabolism are poorly understood despite the importance for fetal development and lifelong health. We aimed to explore fatty acid (FA) processing in human villous placental explants from seven uncomplicated term singleton pregnancies delivered by elective cesarean section. Explants were treated with stable isotope-labeled palmitic acid (13C-PA), oleic acid (13C-OA), or docosahexaenoic acid (13C-DHA) for 3, 24, or 48 hours. Stable isotope-labeled lipids synthesized by placental explants from labeled FA were quantified, alongside endogenous unlabeled placental lipids, by liquid chromatography-mass spectrometry. Labeled phosphatidylcholines (PCs), triacylglycerols (TAGs), and phosphatidylethanolamines were detected in explants, whereas labeled lysophosphatidylcholines were found in both explants and conditioned media. 13C-PA was primarily directed into PC synthesis (74% of 13C-PA-labeled lipids), whereas 13C-OA was directed almost equally into PC and TAG synthesis (45% and 53%, respectively, of 13C-OA-labeled lipids). 13C-DHA was only detectable in TAGs. TAGs demonstrated the highest isotopic enrichment for all 13C-FAs with 13C-OA-TAGs comprising >50% of total OA-TAGs (unlabeled and labeled), consistent with TAGs being a labile and accessible reservoir for FA storage. Variations in lipid incorporation were correlated to maternal glycemia and body mass index, suggesting that this experimental model could be used to investigate the effect of maternal factors on placental lipid metabolism. We conclude that lipid metabolic partitioning of freshly imported FAs into labile and less labile lipid reservoirs in placenta is FA dependent. This process may partly mediate the physiological preferential transplacental transfer of particular FAs to the fetus, but may also be implicated in the fetoplacental pathophysiology of maternal metabolic dysfunction.