Placental ¹³C-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 ¹³C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized ¹³C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results: Maternal BMI positively associated with ¹³C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five ¹³C-DHA triacylglycerols. In turn, ¹³C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most ¹³C-DHA-lipids, but decreased ¹³C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in ¹³C-DHA phosphatidylcholine and ¹³C-DHA lysophospholipids was curtailed, with further decline in ¹³C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in ¹³C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in ¹³C-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.