Placental (13)C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight

BACKGROUND: Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. METHODS: Explants from 17 term placenta were incubated with (13)C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized (13)C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. RESULTS: Maternal BMI positively associated with (13)C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five (13)C-DHA triacylglycerols. In turn, (13)C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most (13)C-DHA-lipids, but decreased (13)C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in (13)C-DHA phosphatidylcholine and (13)C-DHA lysophospholipids was curtailed, with further decline in (13)C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in (13)C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in (13)C-DHA phosphatidylethanolamine plasmalogens were diminished. CONCLUSIONS: Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-021-00344-w.