Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus


 Gestational Diabetes Mellitus (GDM) is the most common medical complication of pregnancy, and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterization of the lipid species in placentas from pregnancies complicated with GDM using high-resolution mass spectrometry lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly a decrease in total placental ceramides. Additionally, very long-chain ceramides and sphingomyelins with 24 carbons were decreased, and glucosylceramides with 16 carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly a decrease in medium and long-chain fatty-acyl carnitine species. The decrease in sphingolipids may affect the secretory function of the placenta, and the decrease in long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.