Placental sphingolipids are altered by maternal obesity and GDM and associated with fetal overgrowth

Abstract

Maternal obesity and GDM increase the risk of fetal overgrowth. It has been shown that maternal adiponectin, decreased with these pregnancy pathologies, stimulates ceramide synthesis regulating placental nutrient transfer and fetal growth. We hypothesized that placental sphingolipid content, particularly ceramides, would be associated with fetal overgrowth in maternal obesity and GDM. Human term placentas from control, obese and obese with GDM women were collected. Lipidomic analysis by LC–MS/MS was performed on placental homogenates and membranes to assess sphingolipid content. Placental expression of enzymes involved in sphingolipid metabolism was studied by immunoblot. One or two-way ANOVA were used to analyze statistical differences on sphingolipid content and sphingolipid-related protein expression between groups and correlation with maternal BMI and z-score were determined with Pearson’s correlation coefficient. Placental ceramides decreased with maternal obesity with and without GDM, particularly in the basal membrane (BM), and were negatively correlated with birthweight and maternal BMI. Expression of ceramide synthase, CerS, was decreased and the expression of ceramidase, ASAH1, increased and positively correlated with birthweight. Sphingolipids such as sphingomyelins (SM) were specifically decreased in the microvillous membrane (MVM) of female placentas and negatively correlated with birthweight. The expression of sphingomyelinase (nSMase) was also positively correlated with maternal BMI and birthweight. Our results suggest a role for sphingolipids, particularly ceramides, in placental membranes in regulating fetal growth in pregnancies complicated by maternal metabolic disease and highlight the importance of fetal sex in establishing placental sphingolipid content in pregnancy pathologies.